CompletedNCT02579850TRIBUTEUpdated Oct 29, 2021

2-arm Parallel Group Study of Fixed Combination of CHF 5993 vs Ultibro® in COPD Patients

A Phase 3 interventional study of CHF 5993 + Ultibro matched placebo and Ultibro + CHF 5993 matched placebo in Chronic Obstructive Pulmonary Disease (COPD), sponsored by Chiesi Farmaceutici S.p.A.. Completed at 1 site in Italy. Open to participants aged 40 Years and older. Per ClinicalTrials.gov, last updated 2021-10-29.

Sponsored by Chiesi Farmaceutici S.p.A. · Phase 3, Interventional, and Treatment

Phase: Phase 3
Study type: Interventional
Enrollment: 1,532
Allocation: Randomized
Ages: 40 Years and older
Sex: All

Study summary

The aim of the present study is to evaluate the superiority of the fixed triple therapy with BDP/FF/GB at a daily dose of 400/24/50 mcg respectively with that of Ultibro® Breezhaler® (DPI), fixed combination of indacaterol 85 mcg and of glycopyrronium 43 mcg in COPD patients.

Read the detailed description

Outpatients attending the hospital clinics/study centres will be recruited. Patients with severe and very severe COPD airflow obstruction according to GOLD 2014 criteria. A total of approximately 2192 patients will need to be screened in order to obtain 1534 (767 per arm) randomized and evaluable patients. Approximately 200 sites will be involved worldwide.

Each patient will perform a total of 8 clinic visits (V0 to V7) during the study.

The Primary objective is to demonstrate the superiority of CHF 5993 pMDI over Ultibro® in terms of moderate and severe COPD exacerbation rate over 52 weeks of treatment.

The Secondary objectives are:

To evaluate the effect of CHF 5993 pMDI on other lung function parameters, patient's health status and clinical outcome measures;
To assess the safety and the tolerability of the study treatments.

A 2-week open-label run-in period under Ultibro® followed by a 52-week randomised treatment period.

The trial design will be optimised to measure exacerbation rates by using the Exacerbations of Chronic Pulmonary Disease Tool (EXACT), developed means of collecting patient-reported outcome (PRO) data, which helps to capture the frequency of exacerbations.

Conditions studied

Chronic Obstructive Pulmonary Disease (COPD)

Browse trials for

Keywords

COPD
COPD Exacerbation
EXACT-PRO

In context

Pulmonary Disease, Chronic Obstructive

4,131 studies on the registry are indexed under Pulmonary Disease, Chronic Obstructive; 697 are open to participants now.

This study's enrollment of 1,532 is above the median of 70 across 2,926 interventional studies indexed under Pulmonary Disease, Chronic Obstructive.

Browse Pulmonary Disease, Chronic Obstructive studies →

Lead sponsor

Chiesi Farmaceutici S.p.A. is the lead sponsor of 182 studies on the registry; 22 are open to participants now.

Of its 17 completed or terminated interventional studies of FDA-regulated products, 11 (65%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 40 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

Male and female ≥ 40 years
Severe or very severe COPD diagnosed for at least 12 months
Current smokers or ex-smokers who quit smoking at least 6 months prior to screening visit, with a smoking history of at least 10 pack years
Post-bronchodilator FEV1 \< 50% of the predicted normal value and a post-bronchodilator FEV1/FVC ratio \< 0.7
Documented history of at least one exacerbation in the 12 months
Patient under double therapy for at least 2 months prior to screening. Double therapy will be defined by treatment with any of the following:
Orally inhaled corticosteroid (ICS) and (long-acting beta2-agonist) LABA ICS and long-acting muscarinic antagonist (LAMA) Orally LABA and LAMA Monotherapy with LAMA for at least 2 months prior to screening
Symptomatic patient at screening with a CAT score ≥ 10.
Cooperative attitude and ability to use correctly the inhalers, the spacer AeroChamber Plus (only to patients who are using a spacer), the electronic devices with COPD questionnaire.

Exclusion criteria

Exclusion :

Pregnant or lactating women and all women physiologically capable of becoming pregnant UNLESS are willing to use one or more of the reliable methods of contraception
Patient with a current clinical diagnosis of asthma with a physician-judged need for inhaled or oral corticosteroid therapy
Patient requiring use of the following medications:
Course of systemic steroids > 3 days for COPD exacerbation in the 4 weeks prior to screening Course of antibiotics for COPD exacerbation > 7 days in the 4 weeks prior to screening Phosphodiesterase-4 inhibitor in the 4 weeks prior to screening Use of antibiotics for a lower respiratory tract infection in the 4 weeks prior to screening
COPD exacerbation requiring prescription of systemic corticosteroids and/or antibiotics or hospitalization during the run-in period
Patient treated with non-cardioselective β-blockers in the month preceding the screening or during the run-in period.
Patient treated with long-acting antihistamines unless taken at stable regimen at least 2 months prior to screening and to be maintained constant during the study or if taken as needed
Patient requiring long term (at least 12 hours daily) oxygen therapy for chronic hypoxemia
Known respiratory disorders other than COPD which may impact the efficacy of the study drug
Patient who have clinically significant cardiovascular condition
Patient with atrial fibrillation (AF): Paroxysmal atrial fibrillation, Persistent, Long standing or Permanent
Abnormal and clinically significant 12-lead ECG that results in active medical problem which may impact the safety of the patient
Patient whose ECG shows QTcF >450 ms for males or QTcF >470 ms for females at screening visit are not eligible (not applicable for patient with pacemaker)
Medical diagnosis of narrow-angle glaucoma, clinically relevant prostatic hypertrophy or bladder neck obstruction would prevent use of anticholinergic agents
History of hypersensitivity to M3 Antagonists, β2-agonist, corticosteroids or any of the excipients contained in any of the formulations used in the trial which may raise contra-indications or impact the efficacy of the study drug
Clinically significant laboratory abnormalities indicating a significant or unstable concomitant disease which may impact the efficacy or the safety of the study drug
Patients with hypokalaemia (serum potassium \<3.5 mEq/L or 3.5 mmol/L) or uncontrolled hyperkalaemia
Unstable concurrent disease which may impact the results of the study
Patients with any history of malignancy likely to result in significant disability or likely to require significant medical or surgical intervention within the next six months (after V1) or with malignancy for which they are currently undergoing radiation therapy or chemotherapy
History of alcohol abuse or substance/drug abuse within 12 months prior to screening visit
Participation in another clinical trial if investigational drug was received less than 8 weeks prior to screening visit

Study design

Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment: 1,532 participants (actual)

Study arms

Experimental
CHF 5993 + Ultibro matched placebo
Fixed triple therapy with BDP/FF/GB 100/6/12.5 mcg (CHF 5993) administered 2 puffs twice daily via pMDI + Fixed combination of indacaterol and of glycopyrronium (Ultibro® Breezhaler®) matched placebo administered once daily via DPI for 52-week treatment. Patient used to take pMDI medication using a spacer will be provided with a new spacer for the study. 7 study visits including : central spirometry tests, Local laboratory, COPD assessment test (visit 1 only), Local laboratory Assessments Saint George's Respiratory Questionnaire EXACT-pro questionnaire
Drug: CHF 5993 + Ultibro matched placebo · Procedure: Central spirometry · Other: COPD assessment test · Procedure: Local laboratory Assessments · Other: Saint George's Respiratory Questionnaire · Other: EXACT-pro questionnaire
Active comparator
Ultibro + CHF 5993 matched placebo
Fixed combination of indacaterol 85 mcg and of glycopyrronium 43 mcg (Ultibro® Breezhaler®) administered once daily via DPI + Fixed triple therapy with BDP/FF/GB (CHF 5993) matched placebo administered 2 puffs twice daily via pMDI for 52-week treatment. Patient used to take pMDI medication using a spacer will be provided with a new spacer for the study. 7 study visits including : central spirometry tests, Local laboratory, COPD assessment test (visit 1 only), Local laboratory Assessments, Saint George's Respiratory Questionnaire, EXACT-pro questionnaire
Drug: Ultibro + CHF 5993 matched placebo · Procedure: Central spirometry · Other: COPD assessment test · Procedure: Local laboratory Assessments · Other: Saint George's Respiratory Questionnaire · Other: EXACT-pro questionnaire

Interventions

DrugCHF 5993 + Ultibro matched placebo
Active medication treatment CHF 5993 and Ultibro matched placebo administered twice a day
Also known as: CHF 5993
DrugUltibro + CHF 5993 matched placebo
Active medication treatment Ultibro and CHF 5993 matched placebo administered twice a day
Also known as: Ultibro Breezhaler
ProcedureCentral spirometry
Central spirometry to assess forced expiratory volume at one second and forced vital capacity
OtherCOPD assessment test
COPD assessment test (CAT) at visit 1
ProcedureLocal laboratory Assessments
ECG + Standard Haematology and Biochemistry
OtherSaint George's Respiratory Questionnaire
Saint George's Respiratory Questionnaire
OtherEXACT-pro questionnaire
daily from randomization (Visit 2) to end of study (Visit 7)

What researchers measure

Primary outcomes

Moderate and severe COPD exacerbation rate over 52 weeks of treatment
Exacerbations will be evaluated at each study visit and collected using EXACT-PRO filled-in by patient every day throughout the study
Time frame: 1 year

Secondary outcomes

Time to first moderate to severe COPD exacerbation
Time frame: 1 year
Rate of severe COPD exacerbation over 52 weeks of treatment
Time frame: 1 year
Rate of moderate COPD exacerbation over 52 weeks of treatment
Time frame: 1 year
Change from Baseline at each visit and over the entire treatment period in pre-dose morning FEV1
Time frame: 1 year

Study locations

1 site

Chiesi Farmaceutici S.p.A.
Parma, 43123, Italy

References and documents

Publications

Vanfleteren L, Fabbri LM, Papi A, Petruzzelli S, Celli B. Triple therapy (ICS/LABA/LAMA) in COPD: time for a reappraisal. Int J Chron Obstruct Pulmon Dis. 2018 Dec 12;13:3971-3981. doi: 10.2147/COPD.S185975. eCollection 2018. PubMed 30587953 ↗
Singh D, Fabbri LM, Vezzoli S, Petruzzelli S, Papi A. Extrafine triple therapy delays COPD clinically important deterioration vs ICS/LABA, LAMA, or LABA/LAMA. Int J Chron Obstruct Pulmon Dis. 2019 Feb 28;14:531-546. doi: 10.2147/COPD.S196383. eCollection 2019. PubMed 30880943 ↗
Singh D, Fabbri LM, Corradi M, Georges G, Guasconi A, Vezzoli S, Petruzzelli S, Papi A. Extrafine triple therapy in patients with symptomatic COPD and history of one moderate exacerbation. Eur Respir J. 2019 May 18;53(5):1900235. doi: 10.1183/13993003.00235-2019. Print 2019 May. PubMed 30792343 ↗
Papi A, Petruzzelli S, Vezzoli S, Georges G, Fabbri LM. Triple therapy for all patients with severe symptomatic COPD at risk of exacerbations. Eur Respir J. 2019 Apr 18;53(4):1900147. doi: 10.1183/13993003.00147-2019. Print 2019 Apr. No abstract available. PubMed 31000665 ↗
Papi A, Vestbo J, Fabbri L, Corradi M, Prunier H, Cohuet G, Guasconi A, Montagna I, Vezzoli S, Petruzzelli S, Scuri M, Roche N, Singh D. Extrafine inhaled triple therapy versus dual bronchodilator therapy in chronic obstructive pulmonary disease (TRIBUTE): a double-blind, parallel group, randomised controlled trial. Lancet. 2018 Mar 17;391(10125):1076-1084. doi: 10.1016/S0140-6736(18)30206-X. Epub 2018 Feb 9. Erratum In: Lancet. 2018 Mar 17;391(10125):1022. doi: 10.1016/S0140-6736(18)30504-X. PubMed 29429593 ↗

Individual participant data

Plan to share: Yes — Chiesi commits to sharing with qualified scientific and medical Researchers, conducting legitimate research, Patient-level Data, Study-level Data, the Clinical Protocol and the full CSR, providing access to clinical trial information consistently with the principle of safeguarding commercially confidential information and patient privacy. Any shared Patient-level Data is anonymized to protect personally identifiable information. Chiesi access criteria and complete process for clinical data sharing is available on the Chiesi Group website.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Oct 29, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02579850
Lead sponsor: Chiesi Farmaceutici S.p.A.
Responsible party: Sponsor
First posted: Oct 20, 2015
Start date: May 29, 2015
Primary completion: Jul 10, 2017
Completion: Jul 10, 2017
Last update: Oct 29, 2021

Study contacts

Mario Scuri, MD

study chair · Chiesi Farmaceutici S.p.A.

Nicolas Roche, Pr

principal investigator · Hopitaux Universitaires Paris Centre - Groupe Hospitalier Cochin

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Oct 2021. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Pulmonary Disease, Chronic Obstructive→

Other studies from this sponsor

Chiesi Farmaceutici S.p.A.

Start the discussion