Pulmonary Disease, Chronic ObstructivePhase 4NCT00680056
Add-on Effects of Tiotropium Over Formoterol in Exercise Tolerance on Chronic Obstructive Pulmonary Disease Patients
A Phase 4 study testing Formoterol plus Tiotropium in people with Pulmonary Disease, Chronic Obstructive and Chronic Bronchitis, run by Federal University of São Paulo at 1 site in Brazil.
Trial summary
The primary objective is to comparatively evaluate the isolated effects of a long-acting beta2-adrenergic (formoterol fumarate 12µg b.i.d. via Aeroliser) and combined with a long-acting anti-cholinergic (tiotropium bromide 18µg o.d via Handihaler) on breathlessness, dynamic hyperinflation and exercise tolerance in… Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Pulmonary Disease, Chronic Obstructive, Chronic Bronchitis, Pulmonary Emphysema
- What is being tested?
- Formoterol plus Tiotropium
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 33 participants
- Where
- 1 siteBrazil
- Study dates
- Nov 2007to Jan 2009
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- COPD patients aged ≥ 40 years with stable moderate-to-severe airflow obstruction (FEV1 < 70% and FEV1/FVC ≤ 70% of predicted normal value) post-bronchodilator
- presenting with a long history of smoking (> 20 pack-years) and chronic breathlessness (Baseline Dyspnoea Index total score < 9)
Who cannot join
- significant cardiovascular disease, hospitalization for COPD exacerbation or presence of a respiratory tract infection within 1 month of screening
- current or childhood asthma
- a history of allergic rhinitis or other atopic disease
- inability to interrupt usual bronchodilator medication
- use of oral steroids within a month before screening
- need for long-term oxygen therapy, arterial oxygen saturation < 85% at rest anemia, hypo- and hyperthyroidism, hyperadrenergic state
- uncontrolled insulin dependent diabetes mellitus, malignancy, or any disease or condition which limits exercise performance other than COPD
- change in inhaled corticosteroid or theophylline use within 1 month prior to screening
Trial locations and contacts
1 site in 1 country.
Brazil1 site
Pulmonary Function and Clinical Exercise Physiology Unit (SEFICE)
São Paulo, São Paulo, 04020-050
About this study
Official title: Randomised Cross-over Study to Compare the Effect of Formoterol Plus Tiotropium Versus Formoterol Monotherapy on Breathlessness, Dynamic Hyperinflation and Exercise Tolerance in Moderate-to-severe Stable COPD Patients
The primary objective is to comparatively evaluate the isolated effects of a long-acting beta2-adrenergic (formoterol fumarate 12µg b.i.d. via Aeroliser) and combined with a long-acting anti-cholinergic (tiotropium bromide 18µg o.d via Handihaler) on breathlessness, dynamic hyperinflation and exercise tolerance in patients with advanced, but stable, chronic obstructive pulmonary disease. The study hypothesis is that combining long acting bronchodilators with different action mechanisms would promote synergistic effects on clinical outcomes.
Read the detailed description
This will be a single center, randomized, double-blind study consisting of two 2-week treatment periods separated by a 5-7 days washout phase without long-acting bronchodilators. Eligible patients who complete the one week screening phase will be randomized to one of two treatment sequences: 1) Formoterol --> Formoterol + Tiotropium or 2) Formoterol + Tiotropium --> Formoterol. During the treatment periods, patients will be allowed to use a short-acting beta2-adrenergic+short-acting anticholinergic as rescue medication (salbutamol+ipratropium via MDI)
- Being tested
- Formoterol plus Placebo (Tiotropium), Formoterol plus Tiotropium
- Keywords
- Pulmonary Disease, Chronic Obstructive, Tiotropium, Formoterol, Bronchodilator Agents, Exercise Tolerance, Randomized Controlled Trial [Publication Type], COPD
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive, Bronchitis, Chronic, Pulmonary Emphysema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Formoterol plus Placebo (Tiotropium)Drug
Formoterol 12mcg-capsules (2x/d) + Placebo (Tiotropium) (1x/d). Double-blind medication will be dispensed in HandiHalers and Aerolisers during 2 weeks.
Formoterol plus TiotropiumDrug
Formoterol 12mcg-capsule (2x/dia) + Tiotropium 18mcg-capsule (1x/d). Double-blind medication will be dispensed in HandiHalers and Aerolisers during 2 weeks.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Formoterol plus Placebo (Tiotropium) Receives: Drug: Formoterol plus Placebo (Tiotropium) |
| 2 | Experimental | Formoterol plus Tiotropium Receives: Drug: Formoterol plus Tiotropium |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage Change in Exercise Tolerance From Baseline at 2 Weeks
Percentage change from baseline in time to the limit of tolerance on a high intensity constant-speed treadmill exercise test (with a speed corresponding to 80% of that obtained during incremental test)
Measured: Baseline and after 2 weeks with each treatment
Secondary outcomes (1)
Mean Score on the Transitional Dyspnea Index (TDI)
TDI is a multidimensional clinical instrument developed to provide a comprehensive assessment of change in dyspnea after an intervention, considering three components (functional impairment, magnitude of task, and magnitude of effort). It ranges from -9 (major deterioration) to +9 (major improvement).
Measured: After 2 week of each treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 May 2008 (estimated)
- Study startNov 2007
- Primary completionDec 2008
- Study completionJan 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pulmonary Disease, Chronic ObstructiveStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Federal University of São Paulo
- Sponsor type
- University, hospital or other
- Investigators
- J Alberto Neder, MD, phD, Principal investigator, Federal University of São Paulo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00680056
- Sponsor's protocol ID
- TIOFOR
- Status last verified
- Oct 2009
- First submitted
- 15 May 2008
- Last updated
- 20 Jan 2010
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Berton DC, Reis M, Siqueira AC, Barroco AC, Takara LS, Bravo DM, Andreoni S, Neder JA. Effects of tiotropium and formoterol on dynamic hyperinflation and exercise endurance in COPD. Respir Med. 2010 Sep;104(9):1288-96. doi: 10.1016/j.rmed.2010.05.017. Epub 2010 Jun 26.
PubMed 20580216
Study at a glance
From the registry record, last updated by the sponsor on 20 Jan 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomised Cross-over Study to Compare the Effect of Formoterol Plus Tiotropium Versus Formoterol Monotherapy on Breathlessness, Dynamic Hyperinflation and Exercise Tolerance in Moderate-to-severe Stable COPD Patients
- ClinicalTrials.gov ID
- NCT00680056
- Acronym / sponsor ID
- TIOFOR
- Keywords
- Pulmonary Disease, Chronic Obstructive, Tiotropium, Formoterol, Bronchodilator Agents, Exercise Tolerance, Randomized Controlled Trial [Publication Type], COPD
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Federal University of São PauloUniversity, hospital or other
- Study start
- Nov 2007
- Primary completion
- Dec 2008 (actual)
- Study completion
- Jan 2009 (actual)
- First posted
- 19 May 2008 (estimated)
- Results
- Posted 3 Dec 2009
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective is to comparatively evaluate the isolated effects of a long-acting beta2-adrenergic (formoterol fumarate 12µg b.i.d. via Aeroliser) and combined with a long-acting anti-cholinergic (tiotropium bromide 18µg o.d via Handihaler) on breathlessness, dynamic hyperinflation and exercise tolerance in patients with advanced, but stable, chronic obstructive pulmonary disease. The study hypothesis is that combining long acting bronchodilators with different action mechanisms would promote synergistic effects on clinical outcomes.
Detailed description
This will be a single center, randomized, double-blind study consisting of two 2-week treatment periods separated by a 5-7 days washout phase without long-acting bronchodilators. Eligible patients who complete the one week screening phase will be randomized to one of two treatment sequences: 1) Formoterol --> Formoterol + Tiotropium or 2) Formoterol + Tiotropium --> Formoterol. During the treatment periods, patients will be allowed to use a short-acting beta2-adrenergic+short-acting anticholinergic as rescue medication (salbutamol+ipratropium via MDI)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: Formoterol plus Placebo (Tiotropium)Formoterol plus Placebo (Tiotropium) |
| 2 | Experimental | Drug: Formoterol plus TiotropiumFormoterol plus Tiotropium |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- COPD patients aged ≥ 40 years with stable moderate-to-severe airflow obstruction (FEV1 < 70% and FEV1/FVC ≤ 70% of predicted normal value) post-bronchodilator
- presenting with a long history of smoking (> 20 pack-years) and chronic breathlessness (Baseline Dyspnoea Index total score < 9)
Key exclusion criteria (8 listed)
- significant cardiovascular disease, hospitalization for COPD exacerbation or presence of a respiratory tract infection within 1 month of screening
- current or childhood asthma
- a history of allergic rhinitis or other atopic disease
- inability to interrupt usual bronchodilator medication
- use of oral steroids within a month before screening
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Formoterol plus Placebo (Tiotropium)Formoterol 12mcg-capsules (2x/d) + Placebo (Tiotropium) (1x/d). Double-blind medication will be dispensed in HandiHalers and Aerolisers during 2 weeks. | Drug | 1 |
| Formoterol plus TiotropiumFormoterol 12mcg-capsule (2x/dia) + Tiotropium 18mcg-capsule (1x/d). Double-blind medication will be dispensed in HandiHalers and Aerolisers during 2 weeks. | Drug | 2 |
Primary outcome
Percentage Change in Exercise Tolerance From Baseline at 2 Weeks
Time frame: Baseline and after 2 weeks with each treatment
Percentage change from baseline in time to the limit of tolerance on a high intensity constant-speed treadmill exercise test (with a speed corresponding to 80% of that obtained during incremental test)
1 secondary outcome
Mean Score on the Transitional Dyspnea Index (TDI)
Time frame: After 2 week of each treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jan 2010.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 20580216Berton DC, Reis M, Siqueira AC, Barroco AC, Takara LS, Bravo DM, Andreoni S, Neder JA. Effects of tiotropium and formoterol on dynamic hyperinflation and exercise endurance in COPD. Respir Med. 2010 Sep;104(9):1288-96. doi: 10.1016/j.rmed.2010.05.017. Epub 2010 Jun 26.
Related trials for Pulmonary Disease, Chronic Obstructive
Active, not recruiting
Symptoms and Functions in Patients With COPD and Chronic Bronchitis Switching From CIG to THS
COPD, Smoking
Not yet recruitingPhase 2/3
An Open-Label Extension Study to Evaluate Inhaled Treprostinil SMI in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Not yet recruiting
The Aim of the Study is to Decipher the Alterations in Signalling Pathways of Skeletal Muscle Stem Cells (Satellite Cells (SCs)) in Individuals With COPD, as Well as to Examine the Effect of Exercise Training on SCs.
COPD (Chronic Obstructive Pulmonary Disease), Sarcopenia in Elderly
Not yet recruitingPhase 2
Study of Treprostinil Administered Via Soft Mist Inhaler (SMI) in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
RecruitingPhase 3
A Study to Investigate the Efficacy and Safety of Belumosudil Compared With Best Available Therapy in Participants Aged 12 Years or Older With Chronic Graft-versus-host Disease
Chronic Graft Versus Host Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
J Alberto Neder, MD, phD principal investigator
Federal University of São Paulo
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Formoterol plus Tiotropium in people with Pulmonary Disease, Chronic Obstructive and Chronic Bronchitis, run by Federal University of São Paulo at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Jan 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Dec 2009). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage Change in Exercise Tolerance From Baseline at 2 Weeks (time frame: Baseline and after 2 weeks with each treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00680056, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jan 2010.