This page shows what was measured, who it was measured in, and what that does not settle.
What Tiotropium does in the body
Long-term airway relaxation with a once-daily inhaler.
A nerve running to the lungs constantly tells the muscle around each airway to stay slightly tightened. Tiotropium sits on the receptor that nerve signal lands on, so the message never arrives and the muscle relaxes. What makes one dose last a full day is not how tightly it binds but how slowly it lets go: it clings to the receptor on airway muscle for about thirty-five hours, while falling off the receptor on the heart in under four. It cannot undo the airway damage underneath, so it makes breathing easier without changing the course of the disease.
What happened in people
Compared with salmeterol, it delayed the next lung flare-up by about six weeks and reduced flare-up risk by 17%.
✓ Reviewed first-read answer
Where this came from
A person wrote this and a reviewer approved it against this exact record. It carries no effect size.
A reviewer approved this against this record. The reviewed-claim record carrying the exact population and effect size does not exist yet.
No source is stored against this line.
The limit that matters most
It did not slow the long-term loss of lung function.
Where it acts
Muscarinic M3 receptors on bronchial smooth muscle and submucosal glands, reached directly by the inhaled particle
Kind of result
The kind of result is not recorded
Supervision
RNAWiki has not recorded a supervision or regulatory status for this substance.
What the registries record it as
The substance registry classes this as chemical.
FDA substance registry · 0EB439235F · read 2026-08-29
Its recorded molecular formula is C19H22NO4S2Br∙H2O.
US prescribing information · 7b656b14-fcaa-2741-f6f0-e0be48971c02 · read 2026-08-30
Where each sentence above came from
No recorded sentence describes the change this makes in a way that stands on its own. The page opens with what it is taken for instead, and the recorded explanation follows below.
Shown as the opening line on this page.
The limit a reviewer approved as the one that matters most here.
The four opening statements run to 126 words.
Words this page uses
Four words worth knowing first
Chosen from what this page shows, with each one explained before the word it depends on.
Comparator
A comparator is whatever the treatment was measured against.
A picture of it, and where the picture fails
It is like the other runner in a race.
Where that stops being true. A race has one winner. A study can show both arms improved.
What people get wrong. Results are read without asking what the other group got. Beating nothing is not beating a treatment.
The control condition against which the experimental intervention is assessed.
Randomisation
Randomisation means chance decides who gets which treatment.
A picture of it, and where the picture fails
It is like a coin toss deciding the groups.
Where that stops being true. A coin toss is fair once. Fairness here comes from doing it for everyone.
What people get wrong. It is thought to make groups identical. It makes them similar on average, including on things nobody measured.
Allocation of participants to arms by a chance process, so that unmeasured factors are balanced in expectation.
Absolute difference
An absolute difference is how many more people in a hundred were affected.
A picture of it, and where the picture fails
It is like counting heads in two rooms of a hundred.
Where that stops being true. Heads are easy to count. Study results carry a margin of error too.
What people get wrong. It is confused with a percentage change, which can look far larger.
The arithmetic difference in event rates between arms.
Confidence interval
A confidence interval is the range the true answer is likely to sit in.
A picture of it, and where the picture fails
It is like a weather forecast giving a range rather than one number.
Where that stops being true. A forecast range covers tomorrow. This one covers what the study could resolve.
What people get wrong. The middle number is read as the answer. A range crossing zero means no change is still possible.
An interval estimate that would contain the true parameter in a stated proportion of repeated studies.
What happened in people◇Read from sources, not yet reviewed
What happened in people
Each card is one study: the exact question it asked, who was in it, and whether it showed what it set out to show.
Co-primary: rate of decline in mean FEV1 before and after bronchodilation, from day 30 onwards
✗ The study did not show it
Who was studied
UPLIFT (NCT00144339)
How many people
5993
Study design
Phase 4, randomised, double-blind, placebo-controlled, four years
Compared against
A dummy treatment
Kind of result
What a body can do day to day
What was found
After day 30 the between-group differences in rate of decline were not significant on either co-primary endpoint. Absolute FEV1 gains of 87 to 103 mL pre-bronchodilator and 47 to 65 mL post-bronchodilator were maintained, P<0.001.
Repeated elsewhere
Unreplicated
What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.
The limits of this study, and where it came from
Main limit. The trial is widely cited for its secondary findings on exacerbations and health status. Its co-primary endpoint — the reason it ran for four years — was not met, and the St George’s Respiratory Questionnaire benefit of 2.3 to 3.3 units sits below the conventional 4-unit threshold for clinical significance.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Inhalation powder in capsules for the HandiHaler device (18 micrograms) and aqueous soft-mist inhalation spray for the Respimat device (2.5 or 5 micrograms)
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Risk of death (noninferiority, Respimat against HandiHaler) and risk of first COPD exacerbation (superiority)
✓ The study showed what it set out to show
Who was studied
TIOSPIR (NCT01126437)
How many people
17135
Study design
Phase 4, randomised, double-blind, device-comparison safety trial, mean 2.3 years
Compared against
Not recorded for this study
Kind of result
Living longer, or avoiding a major event
What was found
Death: Respimat 5 micrograms against HandiHaler hazard ratio 0.96 (95% CI 0.84 to 1.09); 2.5 micrograms hazard ratio 1.00 (0.87 to 1.14). First exacerbation: hazard ratio 0.98 (0.93 to 1.03) — noninferior on death, not superior on exacerbations.
Repeated elsewhere
Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. No limitation is recorded for this study.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Inhalation powder in capsules for the HandiHaler device (18 micrograms) and aqueous soft-mist inhalation spray for the Respimat device (2.5 or 5 micrograms)
Interval reported. 95% CI 0
Written into the record, not signed off as a reviewed claim.
Time to first moderate or severe COPD exacerbation, tiotropium against salmeterol
✓ The study showed what it set out to show
Who was studied
POET-COPD (NCT00563381)
How many people
7376
Study design
Phase 4, randomised, double-blind, double-dummy, active comparator, one year
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Hazard ratio 0.83 (95% CI 0.77 to 0.90), P<0.001; 187 days against 145 days
Repeated elsewhere
Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. No limitation is recorded for this study.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Inhalation powder in capsules for the HandiHaler device (18 micrograms) and aqueous soft-mist inhalation spray for the Respimat device (2.5 or 5 micrograms)
Interval reported. 95% CI 0
Written into the record, not signed off as a reviewed claim.
Peak and trough FEV1 at 24 weeks, and time to first severe exacerbation, added to inhaled glucocorticoid plus long-acting beta-agonist
✓ The study showed what it set out to show
Who was studied
PrimoTinA-asthma (NCT00772538 and NCT00776984)
How many people
912
Study design
Phase 3, two replicate randomised, double-blind, placebo-controlled trials, 48 weeks
Compared against
A dummy treatment
Kind of result
A number that stands in for health
What was found
Trough FEV1 difference 88±31 mL (P=0.01) and 111±30 mL (P<0.001); time to first severe exacerbation 282 against 226 days, hazard ratio 0.79, P=0.03
Repeated elsewhere
Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. This is a third controller added to two, in patients already failing both. The lung-function difference is around 100 mL, which is at the lower edge of what a patient would be expected to notice.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Inhalation powder in capsules for the HandiHaler device (18 micrograms) and aqueous soft-mist inhalation spray for the Respimat device (2.5 or 5 micrograms)
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Trough FEV1 at one year, tiotropium against ipratropium
✓ The study showed what it set out to show
Who was studied
Vincken 2002 — tiotropium against ipratropium, two identical one-year trials
How many people
535
Study design
Phase 3, randomised, double-blind, double-dummy, active comparator, one year
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Trough FEV1 +0.12±0.01 L on tiotropium against -0.03±0.02 L on ipratropium, P<0.001; exacerbations reduced 24%, P<0.01
Repeated elsewhere
Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. No limitation is recorded for this study.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Inhalation powder in capsules for the HandiHaler device (18 micrograms) and aqueous soft-mist inhalation spray for the Respimat device (2.5 or 5 micrograms)
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
RNAWiki holds 5 written-up human studies for this substance, each with the question it asked.
How we know it
Each card names the study, the number of people and what the study set out to measure.
What this does not prove
These summaries were written by a person and have not been signed off as reviewed claims.
Why it matters
A study that failed is as informative as one that worked, and both are here.
What we still do not know
No reviewed claim exists, so no exact population, effect size or interval is published yet.
What it changes in the body◇Read from sources, not yet reviewed
The path through the body
From what a person takes to what changes. A solid line is a step measured in people. A dashed line is a step nobody has measured that way.
Start
Tiotropium
What a person takes: Inhalation powder in capsules for the HandiHaler device (18 micrograms) and aqueous soft-mist inhalation spray for the Respimat device (2.5 or 5 micrograms).
The measurement behind this step
Once daily. The HandiHaler pierces a lactose-blended capsule and depends on the patient generating enough inspiratory flow; the Respimat produces a slow-moving mist mechanically, which removes that dependence. The two devices were compared directly in TIOSPIR and behaved the same on mortality and exacerbations. The label is explicit that neither is a rescue medication.
Getting in
Delivered as a powder from a capsule, or as a slow mist
Two devices exist. One pierces a capsule of powder that is drawn in by the breath; the other pushes a fine mist out slowly enough that it can be inhaled without perfect timing.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
HandiHaler delivers 18 micrograms of tiotropium bromide monohydrate blended with lactose carrier; Respimat delivers 2.5 or 5 micrograms as an aqueous soft mist generated mechanically rather than by propellant. The two were compared directly in 17,135 patients in TIOSPIR and were noninferior on mortality and equivalent on exacerbations.
A permanently charged molecule stays where it lands
The molecule carries a fixed electrical charge, so it does not slip through cell membranes easily. That keeps it in the airway and out of the brain, and means the portion swallowed is barely absorbed.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Tiotropium is a quaternary ammonium compound. The permanent positive charge on the nitrogen limits passive membrane permeation and blood-brain barrier penetration, and the label describes the bronchodilation as predominantly a site-specific effect.
It occupies the receptor the nerve signal was aiming for
Acetylcholine released by the vagus nerve normally lands on a receptor on the airway muscle and makes it contract. Tiotropium sits in that spot instead, and the message has nowhere to arrive.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Competitive, reversible antagonism at muscarinic receptors, with similar affinity across M1 to M5 and the airway effect arising from M3 blockade on smooth muscle. M3 activation normally couples through Gq to phospholipase C, inositol trisphosphate and a rise in intracellular calcium.
It lets go of the lung receptor very slowly and the heart receptor quickly
This is the whole trick. The drug clings to the receptor on airway muscle for about a day and a half, but falls off the one on the heart in a few hours — so the useful effect outlasts the unwanted one.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
Measured dissociation half-lives from human receptors were 34.7 hours at M3, 14.6 hours at M1 and 3.6 hours at M2, against 0.26, 0.11 and 0.035 hours for ipratropium. The authors named this kinetic receptor subtype selectivity: equilibrium affinity is near-identical across subtypes, and only the off-rate distinguishes them. M2 receptors are presynaptic autoreceptors and cardiac; leaving them quickly is desirable.
Airway muscle relaxes, the tube widens, and one inhalation covers twenty-four hours. It also cuts down mucus secretion, which the same nerve signal drives.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Preclinical protection against methacholine-induced bronchoconstriction was dose-dependent and lasted longer than 24 hours. In UPLIFT the absolute FEV1 gain of 87 to 103 mL before bronchodilation was maintained unchanged across four years, which is the signature of a symptomatic bronchodilator rather than a disease-modifying drug.
The damaged lung goes on being lost at the same rate
Blocking the nerve signal removes the part of the narrowing that can still move. It does nothing to destroyed air sacs or scarred small airways, and four years of treatment did not change how fast lung function fell.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
UPLIFT’s co-primary endpoints were the rates of decline in pre- and post-bronchodilator FEV1 from day 30; after day 30 neither differed significantly from placebo. The exacerbation, hospitalisation and respiratory-failure reductions in the same trial are real and are a separate finding from disease modification.
No suggested links are held for this record, so nothing is hidden from this path.
What we know
The record describes 6 steps from taking it to an effect in a person.
How we know it
Each step names the study behind it in the technical detail beside it.
What this does not prove
A change inside the body is a reason to look. It is not a result in a person.
Why it matters
A reader can see exactly where the chain stops being measured in people.
What we still do not know
No reviewed claim binds any of these steps to a named population.
What is missing or unclear◇Read from sources, not yet reviewed
Were people like you studied?
RNAWiki cannot tell whether a study fits you. It can show who was in it, and where the result stops carrying.
Who was studied
People similar to this profile were included.
People with chronic obstructive pulmonary disease as maintenance treatment, and separately people whose asthma stays uncontrolled on an inhaled steroid plus a long-acting beta-agonist, where it is an add-on rather than a replacement.
Who is missing from the studies
Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What the label states about particular groups
On pediatric, the label states: “The safety and efficacy of SPIRIVA RESPIMAT have not been established in pediatric patients less than 6 years of age.”
US prescribing information · 7b656b14-fcaa-2741-f6f0-e0be48971c02 · read 2026-08-30
On older people, the label states: “Based on available data, no adjustment of SPIRIVA RESPIMAT dosage in geriatric patients is warranted [see Clinical Pharmacology (12.3) ].”
US prescribing information · 7b656b14-fcaa-2741-f6f0-e0be48971c02 · read 2026-08-30
On people who are pregnant, the label states: “Risk Summary The limited human data with SPIRIVA RESPIMAT use during pregnancy are insufficient to inform a drug-associated risk of adverse pregnancy-related outcomes.”
US prescribing information · 7b656b14-fcaa-2741-f6f0-e0be48971c02 · read 2026-08-30
On people who are breastfeeding, the label states: “Risk Summary There are no data on the presence of tiotropium in human milk, the effects on the breastfed infant, or the effects on milk production.”
US prescribing information · 7b656b14-fcaa-2741-f6f0-e0be48971c02 · read 2026-08-30
On people with reduced liver function, the label states: “The effects of hepatic impairment on the pharmacokinetics of tiotropium were not studied.”
US prescribing information · 7b656b14-fcaa-2741-f6f0-e0be48971c02 · read 2026-08-30
On people with reduced kidney function, the label states: “Patients with moderate to severe renal impairment (creatinine clearance of <60 mL/min) treated with SPIRIVA RESPIMAT should be monitored closely for anticholinergic side effects [see Dosage and Administration (2) , Warnings and Precautions (5.6) , and Clinical Pharmacology (12.3) ].”
US prescribing information · 7b656b14-fcaa-2741-f6f0-e0be48971c02 · read 2026-08-30
Where the result stopped carrying
UPLIFT missed both co-primary endpoints after four years and 5,993 patients
A 2011 meta-analysis of five trials reported a 52% higher mortality with the Respimat device, relative risk 1.52 (95% CI 1.06 to 2.16)
A 2008 meta-analysis of 17 trials reported a 60% higher risk of cardiovascular death, myocardial infarction or stroke across the anticholinergic class
In asthma the drug is a third agent added to two that are already failing, and buys about 100 mL of trough FEV1
This is a scope explorer, not a diagnosis engine.
It shows who was studied so you can see whether people similar to you were included.
RNAWiki cannot tell whether a study fits you. It can show who was in it.
What it would be like to take◇Read from sources, not yet reviewed
Why it might seem to do nothing
A real effect and a noticed effect are different things. These are the recorded reasons the two come apart.
It was studied in different people
The people in the studies were not much like the reader.
On this record: Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
The evidence may simply be wrong
Small early studies often do not hold up.
On this record: RNAWiki has not yet published a reviewed conclusion for this use.
Other reasons RNAWiki checked and found nothing for (11)
It was studied for a different goal
The studies measured something else entirely. Nothing in this record points to this reason.
A different form was studied
The studied form is not the form on the shelf. Nothing in this record points to this reason.
There was nothing to correct
Where a level is already normal, topping it up may change nothing. Nothing in this record points to this reason.
Something else had to happen too
In the studies it was paired with training, a diet or another treatment. Nothing in this record points to this reason.
The change is too small to feel
A real change can still sit below what a person notices. Nothing in this record points to this reason.
Day-to-day swing hides it
Sleep, food, stress and time of day move most numbers more than this would. Nothing in this record points to this reason.
Not enough time yet
The studies ran longer than the person has waited. Nothing in this record points to this reason.
It was not taken as studied
Missed days change the result, and studies count them. Nothing in this record points to this reason.
Something else changed at the same time
Two changes at once cannot be told apart afterwards. Nothing in this record points to this reason.
The product may not be what it says
Contents of a sold product are not always what the label states. Nothing in this record points to this reason.
No recorded reason
RNAWiki has nothing stored that would explain it. Nothing in this record points to this reason.
None of these is a reason to take more. Taking more is not a step this page ever suggests.
What it would be like to take◇Read from sources, not yet reviewed
What taking it involves
The recorded facts about getting hold of it and using it. Nothing here is a suggestion about what you should do.
How it is supplied
Prescription only
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Read from the recorded approval status.
No source is stored against this line.
Form and route
Inhalation powder in capsules for the HandiHaler device (18 micrograms) and aqueous soft-mist inhalation spray for the Respimat device (2.5 or 5 micrograms)
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form and route recorded on this substance.
No source is stored against this line.
Who oversees it
RNAWiki has not recorded a supervision or regulatory status for this substance.
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
No register row and no identity class settled the question.
No source is stored against this line.
What is in the pack
Once daily. The HandiHaler pierces a lactose-blended capsule and depends on the patient generating enough inspiratory flow; the Respimat produces a slow-moving mist mechanically, which removes that dependence. The two devices were compared directly in TIOSPIR and behaved the same on mortality and exacerbations. The label is explicit that neither is a rescue medication.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on how this is sold and what that means for what is in the pack.
No source is stored against this line.
Where it is registered
Regulatory records are listed in the technical disclosure at the foot of this page.
# Counted from records
Where this came from
A count of rows RNAWiki holds. It describes our records, not your body.
Register entries are stored per jurisdiction and shown with their dates.
No source is stored against this line.
Why people stop
Not recorded.
∅ Nothing recorded
Where this came from
RNAWiki holds nothing here and says so rather than guessing.
No record of why people stopped taking it is stored for this substance.
No source is stored against this line.
What it would be like to take◇Read from sources, not yet reviewed
What can go wrong
Sorted by where each line came from. A regulator's label and a report somebody sent in are not the same kind of fact.
·Worth asking a clinician aboutWritten into the record from the studies named on this page
Not for acute use and not a rescue medication. Immediate hypersensitivity reactions including angioedema, urticaria, rash, bronchospasm and anaphylaxis require immediate discontinuation, and caution applies in patients with hypersensitivity to atropine derivatives or severe hypersensitivity to milk proteins, since the powder is lactose-blended. Life-threatening paradoxical bronchospasm can occur. Worsening of narrow-angle glaucoma and of urinary retention may occur and both are named in the label as reasons to seek immediate advice. The most common adverse reactions above 5% in the one-year placebo-controlled trials were upper respiratory tract infection, dry mouth, sinusitis, pharyngitis, non-specific chest pain, urinary tract infection, dyspepsia and rhinitis.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
Over a long time. No completed tested study window is recorded, so long-term effects are not established by the registry record.
Groups the studies covered thinly. Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What is missing or unclear◇Read from sources, not yet reviewed
Does the exact form matter?
Evidence belongs to the exact thing that was tested. A different salt, a different mixture or a different preparation is a different question.
The form that was studied
Inhalation powder in capsules for the HandiHaler device (18 micrograms) and aqueous soft-mist inhalation spray for the Respimat device (2.5 or 5 micrograms)
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form used in the studies cited on this page.
No source is stored against this line.
What is sold
The HandiHaler pierces a lactose-blended capsule and depends on the patient generating enough inspiratory flow; the Respimat produces a slow-moving mist mechanically, which removes that dependence. The two devices were compared directly in TIOSPIR and behaved the same on mortality and exacerbations. The label is explicit that neither is a rescue medication.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on which forms are sold and how they compare.
No source is stored against this line.
What is recorded as being sold
Recorded price in US: 11.71221 USD per one unit as the pricing file counts it — a tablet, capsule, patch or single item, for the one priced product, as of 2026-08-26, paid by retail pharmacies buying the product, as surveyed by the Centers for Medicare & Medicaid Services. It is not a list price, an insurance price, or what anyone pays at a counter..
Recorded source · 2026-08-26 · read 2026-08-28
Evidence carries across two names for one substance. It does not carry across a salt, a mirror form or a mixture.
What it would be like to take◇Read from sources, not yet reviewed
What you could measure
This one is decided with a clinician, so this section holds questions to ask rather than a plan to run.
RNAWiki could not confidently classify this substance, so no self-experiment plan is offered.
Questions worth asking
Which of the trials of Tiotropium studied people like me?
What was measured, and for how long?
Was the result a laboratory value or a health outcome?
What would we watch for, and when would we stop?
Tracking can show whether something changed for you. It cannot show what caused it.
RNAWiki records evidence. It does not say whether this substance is right for you.
What is missing or unclear◇Read from sources, not yet reviewed
Claims that go past the evidence
Things said about this substance that sound reasonable, and the exact step that is missing between the evidence and the claim.
✗Goes past the evidence
That tiotropium slows the progression of chronic obstructive pulmonary disease — the four-year trial designed to test that did not show it
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That a 2.3 to 3.3 unit St George’s Respiratory Questionnaire difference is a clinically meaningful quality-of-life improvement, against a conventional threshold of 4 units
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That the soft-mist inhaler carries a mortality risk the dry-powder inhaler does not, which a 17,135-patient head-to-head comparison did not reproduce
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That inhaled antimuscarinics raise cardiovascular risk by around 60%, a pooled estimate the two large purpose-built trials did not confirm
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
What is missing or unclear◇Read from sources, not yet reviewed
What nobody knows yet
Open questions, each with why it is open and what would close it.
Missing populations
Which groups were under-represented in the studies has not been recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing long-term data
No completed tested study window is recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
No reviewed conclusion
RNAWiki has not yet published a reviewed conclusion for this use.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing interaction studies
No interaction was found in the registers checked. Not finding one is not the same as showing there is none.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Formulation uncertainty
Several salts, forms or products of Tiotropium are recorded. Results from one form may not transfer to another.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Mechanism not reviewed
No reviewed mechanism story exists for this substance.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
What happened in people◇Read from sources, not yet reviewed
Check any of this yourself
Every line above traced back to the study it came from. This is the technical layer, and the vocabulary changes here.
Every line above can be traced to the study named beside it. Follow the link and read it.
UPLIFT: four years, 5,993 patients, and the co-primary endpoint was not met
In plain words
The trial was built around one question: does this drug slow the rate at which lung function is lost in chronic obstructive pulmonary disease? After four years, the answer was no. Everything else about the trial went well, and that is the part people remember.
What was measured
Rate of decline in FEV1 before and after bronchodilation from day 30 to four years
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
UPLIFT randomised 5,993 patients with a post-bronchodilator FEV1 of 70% predicted or less to tiotropium 18 micrograms once daily or placebo for four years, with all other respiratory medication except inhaled anticholinergics permitted. The co-primary endpoints were the rate of decline in mean FEV1 before and after bronchodilation from day 30 onwards. After day 30 the differences between groups in the rate of decline were not significant on either co-primary endpoint. Absolute FEV1 improvements were maintained throughout — 87 to 103 mL before bronchodilation and 47 to 65 mL after (P<0.001) — and the St George’s Respiratory Questionnaire total score was better on tiotropium at every time point, by 2.3 to 3.3 units (P<0.001). At four years and 30 days tiotropium was associated with reductions in exacerbations, related hospitalisations and respiratory failure.
Written into the record, not signed off as a reviewed claim
The quality-of-life gain in UPLIFT sat below its own clinical threshold
In plain words
The trial reported a statistically significant improvement in a breathing questionnaire at every visit for four years. The size of that improvement was between two and three and a third points, and the smallest change the questionnaire’s author considers clinically meaningful is four.
What was measured
That a 2.3 to 3.3 unit SGRQ difference is a clinically meaningful improvement in quality of life, when the accepted threshold for that instrument is 4 units
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
UPLIFT reported mean absolute St George’s Respiratory Questionnaire total scores lower on tiotropium than on placebo at every time point across four years, ranging from 2.3 to 3.3 units, P<0.001. The threshold for a clinically significant change in the SGRQ is conventionally 4 units, derived empirically by Jones and set out in the standard reference on interpreting these instruments. A difference can be highly significant and smaller than the smallest difference a patient would notice; with 5,993 patients followed for four years, statistical significance is not the constraint. This does not make the finding wrong, and it does make "improved quality of life" a heavier claim than the number supports.
Written into the record, not signed off as a reviewed claim
The Respimat mortality alarm, and the 17,135-patient trial that dissolved it
In plain words
A 2011 meta-analysis of five trials found people using the soft-mist version of tiotropium died more often than those on placebo, a 52% higher risk. Boehringer then ran a single trial larger than all five put together, comparing the two devices directly. The excess was not there.
What was measured
That the soft-mist device carries a mortality risk the dry-powder device does not — an inference from placebo-controlled trials of unequal design that a direct head-to-head comparison in 17,135 patients did not reproduce
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Singh and colleagues pooled five randomised trials of tiotropium delivered by the Respimat soft-mist inhaler against placebo and found all-cause mortality of 90 of 3,686 against 47 of 2,836, relative risk 1.52 (95% CI 1.06 to 2.16, P=0.02, I2=0%), with both the 5 microgram (RR 1.46, 1.01 to 2.10) and 10 microgram (RR 2.15, 1.03 to 4.51) doses implicated, and a number needed to harm of 124 per year. TIOSPIR then randomised 17,135 patients to Respimat 2.5 or 5 micrograms or HandiHaler 18 micrograms and followed them a mean of 2.3 years. Respimat was noninferior to HandiHaler for death — 5 micrograms hazard ratio 0.96 (95% CI 0.84 to 1.09), 2.5 micrograms hazard ratio 1.00 (0.87 to 1.14) — and not superior on first exacerbation (HR 0.98, 0.93 to 1.03). Causes of death and major cardiovascular event rates were similar across the three groups.
Written into the record, not signed off as a reviewed claim
A 2008 meta-analysis put a cardiovascular signal on the whole class
In plain words
Seventeen trials pooled together suggested that inhaled anticholinergics raised the risk of heart attack, cardiovascular death or stroke by about sixty per cent. The two very large trials that came afterwards, together covering 23,000 people, did not find it.
What was measured
That inhaled antimuscarinics raise cardiovascular risk by roughly 60% — a pooled estimate across two molecules and many devices that two purpose-built trials of 23,128 patients did not confirm
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Singh and colleagues pooled 17 randomised trials of inhaled anticholinergics — ipratropium or tiotropium — enrolling 13,645 patients with COPD. The composite of cardiovascular death, myocardial infarction or stroke occurred in 134 of 6,984 (1.9%) on anticholinergics against 83 of 6,661 (1.2%) on control, relative risk 1.60 (95% CI 1.22 to 2.10, P<0.001, I2=0%), with myocardial infarction RR 1.52 (1.04 to 2.22) and cardiovascular death RR 1.92 (1.23 to 3.00). All-cause mortality was RR 1.29 (1.00 to 1.65, P=0.05). UPLIFT, published two weeks later with 5,993 patients over four years, and TIOSPIR, with 17,135 patients over a mean 2.3 years, both reported similar cardiovascular event rates between arms. The meta-analysis pooled two different molecules, several devices and trials designed for other purposes; the trials that followed were designed to answer the question and answered it differently.
Written into the record, not signed off as a reviewed claim
POET-COPD: more exacerbations prevented than by a long-acting beta-agonist
In plain words
A one-year trial put tiotropium directly against salmeterol in more than seven thousand people with chronic obstructive pulmonary disease. Tiotropium delayed the next flare-up by about six weeks and cut the risk of one by seventeen per cent.
What was measured
Time to first moderate or severe exacerbation, tiotropium against salmeterol over one year
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
POET-COPD randomised 7,376 patients with moderate to very severe COPD and an exacerbation in the preceding year to tiotropium 18 micrograms once daily or salmeterol 50 micrograms twice daily, double-blind and double-dummy, for one year. Time to first exacerbation was 187 days against 145 days, hazard ratio 0.83 (95% CI 0.77 to 0.90, P<0.001). Time to first severe exacerbation favoured tiotropium (HR 0.72, 95% CI 0.61 to 0.85, P<0.001), annual moderate or severe exacerbations fell from 0.72 to 0.64 (rate ratio 0.89, 95% CI 0.83 to 0.96, P=0.002) and annual severe exacerbations from 0.13 to 0.09 (rate ratio 0.73, 95% CI 0.66 to 0.82, P<0.001). Deaths were 64 (1.7%) against 78 (2.1%), a comparison the trial was not powered to make.
Written into the record, not signed off as a reviewed claim
PrimoTinA-asthma: a third drug added on top of two, worth about 100 mL and 56 days
In plain words
In people whose asthma stayed uncontrolled on a steroid and a long-acting beta-agonist, adding tiotropium improved lung function by around a tenth of a litre and delayed the next severe attack from about seven and a half months to nine and a half.
What was measured
Peak and trough FEV1 at 24 weeks and time to first severe exacerbation at 48 weeks, added to inhaled glucocorticoid plus long-acting beta-agonist
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Two replicate 48-week randomised placebo-controlled trials enrolled 912 patients already taking inhaled glucocorticoids and long-acting beta-agonists, all symptomatic, with post-bronchodilator FEV1 of 80% predicted or less and at least one severe exacerbation in the previous year. Mean baseline FEV1 was 62% predicted. At 24 weeks the difference in peak FEV1 was 86±34 mL in trial 1 (P=0.01) and 154±32 mL in trial 2 (P<0.001); trough FEV1 differences were 88±31 mL (P=0.01) and 111±30 mL (P<0.001). Time to first severe exacerbation rose from 226 to 282 days, an overall 21% reduction in risk (hazard ratio 0.79, P=0.03). No deaths occurred and adverse events were similar between groups.
Written into the record, not signed off as a reviewed claim
It beat the drug it replaced on lung function and exacerbations
In plain words
Two identical year-long trials compared tiotropium once a day with ipratropium four times a day. Lung function rose on tiotropium and fell on ipratropium, and there were about a quarter fewer flare-ups.
What was measured
Trough FEV1 and exacerbation rate at one year, tiotropium once daily against ipratropium four times daily
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Two identical one-year randomised, double-blind, double-dummy trials compared tiotropium 18 micrograms once daily (n=356) with ipratropium 40 micrograms four times daily (n=179) in patients with screening FEV1 around 40% predicted. Trough FEV1 at one year improved by 0.12±0.01 L on tiotropium and declined by 0.03±0.02 L on ipratropium (P<0.001). Peak expiratory flow, rescue salbutamol use, Transition Dyspnea Index focal score and St George’s Respiratory Questionnaire total and impact scores all improved on tiotropium (P<0.01). Exacerbations fell by 24% (P<0.01), with longer time to first exacerbation (P<0.01) and to first hospitalisation for exacerbation (P<0.05). Apart from more dry mouth on tiotropium, adverse events were similar.
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What is not here
8 questions this page could not answer
These sections were prepared and left out because there was nothing to put in them. They are listed rather than hidden, so the gaps in this record are visible.
What was measured, goal by goal — found nothing in the sources checked.
How close this is to real life — found nothing in the sources checked.
Felt, measured, or meaningful — found nothing in the sources checked.
How long anything takes — found nothing in the sources checked.
What it may clash with — found nothing in the sources checked.
Other ways to the same goal — found nothing in the sources checked.
How this medicine reached us — found nothing in the sources checked.
What changed on this page — found nothing in the sources checked.
The record as stored
The full record, for auditing
Everything above is built from what is below. This layer keeps the technical vocabulary, record identifiers and every stored row, so a reader who wants to check the page can.
The older medicine-wide conclusion held in this record
Written for a clinical reader, and about the medicine as a whole rather than about one indication, population and set of trials. RNAWiki does not treat it as a programme conclusion and no reviewer has signed it off in that form. It is here word for word because it is what the record holds.
A muscarinic antagonist that stays stuck to the M3 receptor for a day and a half while falling off M2 in three and a half hours, which is what makes one inhalation last twenty-four hours; over four years in 5,993 people it held a 87 to 103 mL gain in lung function, cut exacerbations and hospitalisations, and did not change the rate at which lung function declined — the co-primary endpoint the trial existed to answer.
Recorded evidence blocks (9)
Q1
On the Tiotropium label: indicated for what?
"SPIRIVA RESPIMAT is an anticholinergic indicated for: The long-term, once-daily, maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD), and for reducing COPD exacerbations ( 1.1 ) The long-term, once-daily, maintenance treatment of asthma in patients 6 years of age and…": indications and usage on Tiotropium's label. DailyMed label · 7b656b14-fcaa-2741-f6f0-e0be48971c02 · 2026-08-17
Q2
261 registered trials of Tiotropium — at which phases?
Registered studies posting no result
127 of 261
261 registered studies of Tiotropium: 88 phase3, 72 phase4, 40 phase2, 29 na or unstated, 26 phase1, 8 na, 2 early phase1. CLINICALTRIALS_SNAPSHOT · 2026-09-01
456 with a PubMed record
Show the evidence
phase3
88
phase4
72
phase2
40
na or unstated
29
phase1
26
na
8
6 more recorded rows
early phase1
2
completed
230
terminated
14
unknown
11
withdrawn
5
suspended
1
recorded 2026-09-01 · last checked 2026-09-04
Q3
15 of Tiotropium's trials stopped: safety, accrual/recruitment, funding/business, other?
safety (1), accrual/recruitment (8), funding/business (1) and other (5): Tiotropium's stop wording, clustered. CLINICALTRIALS_SNAPSHOT · 2026-09-01
"Difficulty in recruting patients"; 15 of 261 registered studies
Show the evidence
Trial
NCT00394485
terminated; "Difficulty in recruting patients"
NCT00546234
withdrawn; "No subjects enrolled and no ongoing funding."
NCT00706446
terminated; "Funding was terminated"
NCT00783250
terminated; "Problems with data collection"
NCT01715311
withdrawn; "withdrawn prior to patient recruitment"
NCT02275481
terminated; "lack of enrollment"
9 further recorded trials
NCT03199976
terminated; "Subjects in the Salbutamol group discontinued the intervention more often due to troublesome respiratory symptoms"
NCT03219866
terminated; "Lower enrollment than Sponsor expected - Sponsor stopped study"
NCT03376932
withdrawn; "withdrawn due to internal reasons"
NCT03662711
terminated; "Contract terminated between AIFA and the Sponsor (University of Ferrara)"
NCT04990167
terminated; "Difficult enrollment"
NCT05362487
terminated; "Insufficient recruitment"
NCT05838703
withdrawn; "Study halted prematurely due to funding, prior to enrollment of first participant"
NCT06282861
terminated; "Delays in the opening and activation of participating sites, and a low recruitment rate, with only 48 participants enrolled over the course of one year"
NCT07541378
suspended; "Recruitment was temporarily suspended pending additional funding and activation of additional study centers. The pilot phase has been completed and is currently being evaluated. The suspension was not related to safety concerns."
recorded 2026-09-01 · last checked 2026-09-04
Q4
Human studies of Tiotropium used tiotropium inhalation capsules (18 mcg once daily) — over how long?
Human studies of Tiotropium used "tiotropium inhalation capsules (18 mcg once daily)". ClinicalTrials.gov · 2026-09-01
20 recorded entries; human; inhalation; also "Tiotropium (Spiriva) inhalation capsule 18 ug", "Tiotropium bromide 18mcg", "Tiotropium (18 µg o.d.)"
Show the evidence
human
NCT00274092
inhalation; tiotropium inhalation capsules (18 mcg once daily)
NCT00292448
inhalation; Tiotropium (Spiriva) inhalation capsule 18 ug
NCT00361959
Tiotropium bromide 18mcg
NCT00463567
Tiotropium (18 µg o.d.)
NCT00496470
Spiriva (tiotropium bromide 18ug)
NCT00525512
tiotropium 18 mcg
14 more recorded rows
humanNCT00737100
Tiotropium bromide 5 mcg
humanNCT00737100
tiotropium bromide-low dose-2.5mcg
humanNCT00846586
Tiotropium 18 μg
humanNCT01040689
Tiotropium 18 mcg
humanNCT01085045
Tiotropium bromide 18 μg (Spiriva Handihaler®)
humanNCT01126437
tiotropium 1.25 mcg (2 actuations/day)
humanNCT01126437
tiotropium 2.5 mcg (2 actuations/day)
humanNCT01222533
Tiotropium 18mcg
humanNCT01316380
tiotropium 2.5 mcg
humanNCT01316380
tiotropium 5 mcg
humanNCT01627327
tiotropium bromide 18mcg
humanNCT01656005
Spiriva 18mcg
humanNCT01715311
Tiotropium 18 mcg od via single-dose dry powder inhaler
humanNCT01762800
fluticasone propionate/salmeterol 50/250mcg and tiotropium 18mcg
recorded 2026-09-01 · last checked 2026-09-04
Q5
Tiotropium's half-life is 44 hours — which schedules were studied?
44 hours; Excretion The terminal half-life of tiotropium in COPD and asthma patients following once daily inhalation is 25 and 44 hours, respectively.
bioavailabilitypharmacokinetics
2 %; Oral solutions of tiotropium have an absolute bioavailability of 2% to 3%.
metabolismpharmacokinetics
Elimination Metabolism The extent of metabolism is small.
recorded 2026-08-17 · last checked 2026-09-04
Q6
Which 70 trials of Tiotropium posted no result?
Posted no result
70 of 70 completed trials
Registrations
NCT00274027, NCT00274040, NCT00274534, NCT00274014, NCT00274079 and NCT00274092, and 64 more
Completion dates
oldest 2003-03; newest 2023-12-31
Show the evidence
Trial
NCT00274027
2003-03
NCT00274040
2003-03
NCT00274534
2003-07
NCT00274014
2003-10
NCT00274079
2003-10
NCT00274092
2003-10
14 further recorded trials
NCT00239408
2004-04
NCT00274053
2004-04
NCT00239447
2004-04-29
NCT00277264
2004-05
NCT00239499
2004-08
NCT00405236
2005-01
NCT00144196
2005-07-25
NCT00570544
2005-08
NCT00144326
2005-10
NCT00361959
2006-02
NCT00152984
2006-04
NCT00157235
2006-04
NCT00279019
2006-06-13
NCT00308191
2006-12
Q7
At the median, Tiotropium's trials enrolled 163 people — anything larger?
Median enrolment
163
Largest enrolment
116133
Registered trials counted
261
Q8
What do 10053 spontaneous reports say about Tiotropium — and not say?
These are reports people sent to a regulator. They do not show the medicine caused the reaction. Nobody counted how many people took the medicine and reported nothing. The same event can be reported more than once, and many reports are incomplete. News coverage, lawsuits and new warnings change how often people report. A count is not a rate and not a risk.
Tiotropium appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 10053 reaction mentions were counted: dyspnoea 2329; asthma 1679; cough 1073; wheezing 1019. FAERS via Open Targets · CHEMBL1900528 · 2026-06-24
Show the evidence
dyspnoea
2329
asthma
1679
cough
1073
wheezing
1019
chronic obstructive pulmonary disease
852
therapeutic product effect incomplete
792
4 more recorded rows
pneumonia
698
obstructive airways disorder
632
blood count abnormal
530
loss of personal independence in daily activities
449
recorded 2026-06-24 · last checked 2026-09-04
Q9
Which 10 reactions does Tiotropium's label not list?
ChEMBL 37 — CC BY-SA 3.0 Unported · ClinicalTrials.gov — US Government work · Open Targets 26.06 — CC0 · mixed register set; per-register licences in docs/specs/corpus-20k-sources.md · openFDA / DailyMed — US Government work
✗ required summary fields resolved: 4 required field(s) not terminal: Why people use it, Best-supported result, Biggest unanswered question, Human evidence
✓ public claims reviewed: 0 reviewed claim(s); drafts are never rendered
✓ source coverage passed: 6 source rows
✓ no critical contamination: no quarantine open
✓ canonical metadata passed: slug and display name present
✓ no raw internal fields: enforced by the copy-contract test over the rendered page
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