Chronic Obstructive Pulmonary DiseasePhase 4COMBINENCT02055352

Study to Evaluate Efficacy/Safety of Combination Budesonide/Indacaterol vs Fluticasone/Salmeterol in Patients With COPD

A Phase 4 study testing Budesonide, Fluticasone and Indacaterol in people with Chronic Obstructive Pulmonary Disease, run by Novartis Pharmaceuticals at 25 sites in 8 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

To demonstrate the free combination of budesonide and indacaterol is as efficacious as fluticasone and salmeterol in patients with COPD Read more about this study

Who is it for?: Ages 40 years and older
Conditions the study is for: Chronic Obstructive Pulmonary Disease
What is being tested?: Budesonide, Fluticasone and Indacaterol
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 222 participants
Where: 25 sitesin 8 countries
Study dates: 30 May 2014to 26 Jan 2016
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

Written informed consent must be obtained before any assessment is performed
Outpatients with stable COPD groups C and D according to the 2011 GOLD Guidelines.
Current or ex-smokers who have a smoking history of at least 10 pack years
Patients with a history of at least one exacerbation.
Patients able to read and complete

Who cannot join

Use of other investigational drugs within 30 days
Patients with a history of hypersensitivity to any of the study drugs
History or current diagnosis of ECG abnormalities
Patients with diabetes Type I or uncontrolled diabetes Type II including patients with a history of blood glucose levels consistently outside the normal range
Patients who have not achieved an acceptable spirometry result at Visit 1
Patients with a body mass index (BMI) of more than 40 kg/m2

Show all 19Show fewer

Patients with lung cancer or a history of lung cancer
Patients with a history of malignancy of any organ system
Pregnant or nursing (lactating) women
Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment
Patients who do not maintain regular day/night, waking/sleeping cycles (e.g., night shift workers)
Patients that are uncontrolled or unstable on permitted therapy, who in the opinion of the investigator, have clinically significant renal, cardiovascular, neurological, endocrine, immunological, psychiatric, gastrointestinal, hepatic, or haematological abnormalities which could interfere with the assessment of the efficacy and safety of the study treatment
Patients requiring oxygen therapy for chronic hypoxemia
Patients who have had a respiratory tract infection within 6 weeks prior to Visit 1
Patients with concomitant pulmonary disease, e.g. pulmonary tuberculosis, bronchiectasis, sarcoidosis, interstitial lung disorder or pulmonary hypertension
Patients with a known diagnosis of Alpha-1 Antitrypsin deficiency.
Patients with history of lung surgery
Patients who are participating in the active phase of a supervised pulmonary rehabilitation program.
Patients with a history of asthma Other protocol-defined inclusion/exclusion criteria may apply

Trial locations and contacts

25 sites in 8 countries.

Country

City, postcode or hospital

25 sites in 8 countries

Argentina9 sites

Novartis Investigative Site
Buenos Aires, Buenos Aires, C1125ABE
Novartis Investigative Site
Caba, Buenos Aires, C1056ABJ
Novartis Investigative Site
Ciudad Autonoma de Bs As, Ciudad Autonoma de Bs As, C1425FVH
Novartis Investigative Site
Florida, Buenos Aires, B1602DQD
Novartis Investigative Site
La Plata, Buenos Aires, 1900
Novartis Investigative Site
Salta, Salta Province, 4000
Novartis Investigative Site
Santa Rosa, La Pampa Province
Novartis Investigative Site
Vicente López, Buenos Aires, B1638AAI
Novartis Investigative Site
Zárate, Buenos Aires, 2800

Other trials in Argentina

Brazil4 sites

Novartis Investigative Site
Porto Alegre, Rio Grande do Sul, 90880-480
Novartis Investigative Site
Rio de Janeiro, Rio de Janeiro, 021941-617
Novartis Investigative Site
São Bernardo do Campo, São Paulo, 09750-420
Novartis Investigative Site
São Paulo, São Paulo, 01244-030

Other trials in Brazil

Mexico4 sites

Novartis Investigative Site
León, Guanajuato, 37000
Novartis Investigative Site
Mexico City, Mexico City, 03310
Novartis Investigative Site
Mexico City, Mexico City, 06760
Novartis Investigative Site
Mexico City, Mexico City, 14050

Other trials in Mexico

Chile2 sites

Novartis Investigative Site
Rancagua, Rancagua, 2841959
Novartis Investigative Site
Santiago, Santiago Metropolitan, 8431633

Other trials in Chile

Dominican Republic2 sites

Novartis Investigative Site
Santo Domingo, Republica Dominicana, 10205
Novartis Investigative Site
Santo Domingo, Republica Dominicana

Other trials in Dominican Republic

Honduras2 sites

Novartis Investigative Site
San Pedro Sula, Honduras, 21102
Novartis Investigative Site
Tegucigalpa, Honduras

Other trials in Honduras

Ecuador1 site

Novartis Investigative Site
Guayaquil, Guayas, 412

Other trials in Ecuador

Panama1 site

Novartis Investigative Site
Panama City, Provincia de Panamá

Other trials in Panama

About this study

Official title: 24-week Study to Evaluate Efficacy and Safety of the Combination Budesonide / Indacaterol vs Fluticasone / Salmeterol in Patients With COPD

To demonstrate the free combination of budesonide and indacaterol is as efficacious as fluticasone and salmeterol in patients with COPD

Conditions: Chronic Obstructive Pulmonary Disease
Being tested: Budesonide, Fluticasone, Indacaterol, Salmeterol
Medical subject headings: Pulmonary Disease, Chronic Obstructive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

BudesonideDrug
Budesonide 400 mcg twice a day via Breezhaler® device
FluticasoneDrug
Fluticasone 250 mcg twice daily via Accuhaler® device
IndacaterolDrug
Indacaterol 150 mcg once daily via Breezhaler® device
SalmeterolDrug
Salmeterol 50 mcg twice daily via Diskus® device

Study groups in NCT02055352
Study group	Role	What they receive
Budesonide/indacaterol	Experimental	Participants will receive a fixed combination of fluticasone and salmeterol during 4 weeks followed by a free combination of budesonide and indacaterol for the remainig of study. Receives: Drug: Budesonide; Drug: Fluticasone; Drug: Indacaterol; Drug: Salmeterol
Fluticasone / salmeterol	Active comparator	Fixed combination of fluticasone and salmeterol Receives: Drug: Fluticasone; Drug: Salmeterol

What is being measured

The primary outcome is the main question the study is designed to answer.

Change From Baseline in Trough Forced Expiratory Volume in 1 Second (Non-inferiority Analysis).
Forced Expiratory Volume in 1 second (FEV1) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation.
Measured: Baseline and week 12

Secondary outcomes (4)

Change in Health Status - mMRC
Modified Medical Research Council scale (mMRC) questionnaire will be completed by participants. 0 Not troubled with breathlessness except with strenuous exercise; 1 Troubled by shortness of breath when hurrying on the level or walking up a slight hill; 2 Walks slower than people of the same age on the level because of breathlessness or has to stop for breath when walking at own pace on the level; 3 Stops for breath after walking about 100 yards or after a few minutes on the level; 4 Too breathless to leave the house or breathless when dressing or undressing
Measured: Baseline, week 12 and week 24
Change From Baseline in Mean Daily Number of Puffs of Rescue Medication Used Over the 24 Week Treatment
A day with no rescue medication use is defined from the diary data as any day where the patient recorded no rescue medicine use during the previous 12 hours.
Measured: 24 weeks
Change From Baseline in Trough Forced Expiratory Volume in 1 Second at Week 24 (Analysis of Superiority)
Forced Expiratory Volume in 1 second (FEV1) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured through spirometry testing.
Measured: Baseline and week 24
Change in Health Status - SGRQ-C
St George's Respiratory Questionnaire short version questionnaire will be completed by participants. The SGRQ ranges from 0 (no impairment of quality of life) to 100 (highest impairment of quality of life)
Measured: Baseline, week 12 and week 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

30 May 201426 Jan 2016

First posted5 Feb 2014 (estimated)
Study start30 May 2014
Primary completion26 Jan 2016
Study completion26 Jan 2016

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.
Other trials for Chronic Obstructive Pulmonary DiseaseStudies of the same condition, open and under way.
More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
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: Parallel groups
Masking: None (open label)
Enrolment: 222 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02055352
Sponsor's protocol ID: CQAB149BAR01
Acronym: COMBINE
Status last verified: Apr 2017
First submitted: 3 Feb 2014
Last updated: 18 Apr 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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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.
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All Chronic Obstructive Pulmonary Disease trials

Study at a glance

From the registry record, last updated by the sponsor on 18 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 24-week Study to Evaluate Efficacy and Safety of the Combination Budesonide / Indacaterol vs Fluticasone / Salmeterol in Patients With COPD
ClinicalTrials.gov ID: NCT02055352
Acronym / sponsor ID: COMBINE / CQAB149BAR01
Conditions: Chronic Obstructive Pulmonary Disease
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 222 participants (actual)
Lead sponsor: Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: 30 May 2014 (actual)
Primary completion: 26 Jan 2016 (actual)
Study completion: 26 Jan 2016 (actual)
First posted: 5 Feb 2014 (estimated)
Results: Posted 18 Apr 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

To demonstrate the free combination of budesonide and indacaterol is as efficacious as fluticasone and salmeterol in patients with COPD

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Budesonide/indacaterol	Experimental	Drug: Budesonide, Drug: Fluticasone, Drug: Indacaterol, Drug: SalmeterolParticipants will receive a fixed combination of fluticasone and salmeterol during 4 weeks followed by a free combination of budesonide and indacaterol for the remainig of study.
Fluticasone / salmeterol	Active comparator	Drug: Fluticasone, Drug: SalmeterolFixed combination of fluticasone and salmeterol

Who may qualify

Ages: 40 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Written informed consent must be obtained before any assessment is performed
Outpatients with stable COPD groups C and D according to the 2011 GOLD Guidelines.
Current or ex-smokers who have a smoking history of at least 10 pack years
Patients with a history of at least one exacerbation.
Patients able to read and complete

Key exclusion criteria (19 listed)

Use of other investigational drugs within 30 days
Patients with a history of hypersensitivity to any of the study drugs
History or current diagnosis of ECG abnormalities
Patients with diabetes Type I or uncontrolled diabetes Type II including patients with a history of blood glucose levels consistently outside the normal range
Patients who have not achieved an acceptable spirometry result at Visit 1

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
BudesonideBudesonide 400 mcg twice a day via Breezhaler® device	Drug	Budesonide/indacaterol
FluticasoneFluticasone 250 mcg twice daily via Accuhaler® device	Drug	Budesonide/indacaterol, Fluticasone / salmeterol
IndacaterolIndacaterol 150 mcg once daily via Breezhaler® device	Drug	Budesonide/indacaterol
SalmeterolSalmeterol 50 mcg twice daily via Diskus® device	Drug	Budesonide/indacaterol, Fluticasone / salmeterol

Primary outcome

Change From Baseline in Trough Forced Expiratory Volume in 1 Second (Non-inferiority Analysis).
Time frame: Baseline and week 12
Forced Expiratory Volume in 1 second (FEV1) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation.

4 secondary outcomes

Change in Health Status - mMRC
Time frame: Baseline, week 12 and week 24
Change From Baseline in Mean Daily Number of Puffs of Rescue Medication Used Over the 24 Week Treatment
Time frame: 24 weeks
Change From Baseline in Trough Forced Expiratory Volume in 1 Second at Week 24 (Analysis of Superiority)
Time frame: Baseline and week 24
Change in Health Status - SGRQ-C
Time frame: Baseline, week 12 and week 24

Results and safety

Results posted to the registry on 18 Apr 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Budesonide/Indacaterol	109	103
Fluticasone / Salmeterol	113	96

Primary outcome: Change From Baseline in Trough Forced Expiratory Volume in 1 Second (Non-inferiority Analysis).

Time frame: Baseline and week 12. Least squares mean (Standard Error). Unit: Liters

Measure	Budesonide/Indacaterol n = 108	Fluticasone / Salmeterol n = 111
Value	0.080 (0.027)	0.019 (0.028)

Budesonide/Indacaterol vs Fluticasone / Salmeterol: p = 0.004, Mixed effects General linear model

Population analysed: Per-protocol set (PPS) included all patients in the FAS without any major protocol deviations. Major protocol deviations were defined in the validation analysis plan prior to database lock and the unblinding of the study. Patients were analyzed according to the treatment they are randomized to

4 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Budesonide / Indacaterol (A)	10 of 109 (9.2%)	24 of 109 (22%)	Not reported
Fluticasone / Salmeterol (B)	9 of 113 (8%)	39 of 113 (34.5%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Apr 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Chronic Obstructive Pulmonary Disease

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.
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Study of Treprostinil Administered Via Soft Mist Inhaler (SMI) in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
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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.

Novartis Pharmaceuticals study director

Novartis Pharmaceuticals

25 sites in 8 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Budesonide, Fluticasone and Indacaterol in people with Chronic Obstructive Pulmonary Disease, run by Novartis Pharmaceuticals at 25 sites in 8 countries.

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 5 inclusion and 19 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 18 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 25 sites in Argentina, Brazil, Mexico, Chile, Dominican Republic and 3 more countries. 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 18 Apr 2017). 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?

Change From Baseline in Trough Forced Expiratory Volume in 1 Second (Non-inferiority Analysis). (time frame: Baseline and week 12). 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 NCT02055352.

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 18 Apr 2017.