Efficacy and Safety of ICS/LABA vs. LAMA/LABA in Patients With Different COPD Phenotypes.

April 18, 2022 updated by: Alejandra Ramirez Venegas, National Institute of Respiratory Diseases, Mexico

Efficacy and Safety of Fluticasone Furoate/Vilanterol vs. Umeclidinium/Vilanterol in Patients With COPD-asthma Phenotype vs. Emphysema Phenotype. A Controled Clinical Trial.

This is a randomized, blinded, controlled clinical trial for mexican COPD patients.

Biomass smoke associated COPD (BS-COPD) clinical spectrum is different to the one seen in tobacco smoke associated COPD (TS-COPD). BS-COPD patients present COPD-asthma phenotype or asthma-COPD overlap syndrome (ACOS), TS-COPD patients present mostly the emphysema phenotype. BS-COPD patients have a greater risk of exacerbations in comparison to the emphysema phenotype. Therefore, individualizing treatment in both phenotypes may be very useful among the clinical practitioners.

The investigators expect treatment with FF/V to be superior in preventing COPD exacerbations than the U/V combination in patients with COPD-asthma phenotype; andU/V to be superior than FF/V in patients with the emphysema phenotype.

The general objective of the study is to determine the exacerbations outcome in patients with COPD-asthma vs emphysema phenotype patients, treated with both drugs. Secondary objectives include assessment of pulmonary function tests, quality of life, dyspnea and functional capacity change after a 24 weeks treatment.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Type and duration of the investigation: A randomized, blinded, controlled clinical trial; longitudinal, prospective, 3 years (Sep-2017 through Sep-2020).

Background: COPD associated to biomass smoke (BS-COPD) represents the third of all COPD cases in Latin America, and almost the 2% in general population prevalence studies. BS-COPD clinical spectrum is different to the one seen in COPD associated to tobacco smoke (TS-COPD). While BS-COPD patients present COPD-asthma phenotype or asthma-COPD overlap syndrome (ACOS), TS-COPD patients present mostly the emphysema phenotype.

COPD-asthma phenotype in BS-COPD, probably explains that they have a greater risk of exacerbations in comparison to the emphysema phenotype. Therefore, individualizing treatment in both phenotypes may be very useful among the clinical practitioners, because even though those patients are not included in traditional clinical trials, they are part of every day's practice.

In this sense, providing a specific treatment in this group of patients could change the disease progression, improving symptoms, quality of life, reducing costs, side effects and exacerbations. The investigators hypothesize that COPD-asthma phenotype or asthma-COPD overlap syndrome (ACOS), may get a greater benefit by using a combination LABA/ICS (Fluticasone Furoate/Vilanterol - FF/V) therapy, whereas those with the emphysema phenotype with LABA/LAMA (Umeclidinium/Vilanterol U/V) therapy

The upside of these drugs is that both of them have the same easy-to-use device, and it is inhaled once a day only. Their efficacy and safety have been tested in TS_COPD but not in BS-COPD. This trial will allow us to have a clinically and functionally characterization (using biological markers) of the BS-COPD phenotype and to compare those patients with those with the emphysema phenotype.

Hypothesis: Treatment with FF/V will be superior in preventing COPD exacerbations than the U/V combination in patients with COPD-asthma phenotype; while U/V will be superior than FF/V in patients with the emphysema phenotype.

General objective: To determine the exacerbations outcome (exacerbations free interval, exacerbations frequency, severe exacerbations that needed hospitalization frequency, exacerbations frequency according to absolute and percentage (>3%) blood eosinophils, exacerbations percentage for emphysema phenotype and COPD-asthma phenotype) in patients with COPD-asthma vs emphysema phenotype patients, treated with Fluticasone Furoate/Vilanterol 100/25 mcg/day vs Umeclidinium/Vilanterol 55/25 mcg/day, after 6 months of treatment.

Secondary objectives: To determine in both groups: (1) Pulmonary function change (FEV1, FVC and inspiratory capacity) (2) Impulse oscillometry resistance change (3) FeNO change (5) Quality of life change (CAT and Saint George) (6) Dyspnea change (mMRC, BDI y TDI) (7) Functional capacity change (6MWT distance). (8) To characterize and establish the frequency of the COPD-asthma phenotype in BS-COPD patients and emphysema-phenotype in TS-COPD patients.

Methods: Randomized double blind controlled clinical trial. Patients with at least one exacerbation in the last 12 months (confirmed by the prescription of antibiotic and/or oral steroid), and a smoking index > 10 packs/year or a biomass smoke exposition index > 100 hours/year. One hundred BS-COPD patients and one hundred TS-COPD patients will be included; both groups will be exposed to the two treatment options. Fifty patients from each group (BS-COPD and TS-COPD) will be assigned with FF/V and 50 from each group with U/V. Emphysema phenotype and air-trapping pattern will be determined with a CT image. All CTs will be assessed by a radiologist. Baseline DLco will also be correlated with the emphysema CT findings. Blood eosinophils, blood levels IgE, bronchodilator reversibility and baseline FeNO. Rate of exacerbations will be determined in both groups for a time period of 6 months. At the end of the study, the phenotype of each patient will be determined and treatment efficacy will be evaluated according to the phenotype. The sample size was chosen conventionally by considering that there are no other centers with a BS-COPD cohort. Treatment will be randomly assigned using a random numbers table. Safety evaluation includes severe adverse events (SAE) assessment (mainly pneumonia). During the informed consent signing visit (day -15), BS-COPD or TS-COPD diagnosis will be confirmed. There will be four in-clinic visits (baseline; +30 days; +90 days and +180 days) where the symptoms diary will be evaluated to determine the rate of exacerbations or other health resources use. Also, pulmonary function tests (spirometry pre and post-BD, IC) and functional capacity tests (6MWT) will be performed by each patient. Health related quality of life (SGRQ and CAT) and dyspnea (mMRC and BDI/TDI) questionnaires will also performed. There will be three telephonic visits (+60 days, +120 days, +210 days) where adverse events, concomitant medication, other health resources use and exacerbations since last visit will be assessed.

Study Type

Interventional

Enrollment (Actual)

133

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Mexico
    • Tlalpan
      • Mexico City, Tlalpan, Mexico, 14080
        • National Institute of Respiratory Diseases 'Ismael Cosío Villegas'

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients aged 40 to 80 years
  • Men and women (not fertile, not pregnant, or those with a effective birth control method)
  • COPD diagnosis according to GOLD 2017 criteria with a FEV1 ≥ 30%
  • Biomass smoke exposition index ≥ 100 hours/year or smoking index ≥ 10 packs/year,
  • Patients with at least two exacerbations in the last 12 months (confirmed by the prescription of antibiotic and/or oral steroid)
  • Patients with stable COPD (no exacerbations or respiratory infections in the 4 weeks prior inclusion).

Exclusion Criteria:

  • Patients with allergies or intolerance to study medications
  • Female patients on pregnancy, lactancy
  • Patients with cancer diagnosis
  • Patients with bronchiectasis, tuberculosis, recent COPD exacerbation, or any respiratory infection or cardiovascular anomaly that withholds the respiratory function test

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Biomass Smoke COPD

Fluticasone Furoate/Vilanterol 100/25 mcgs. Dry powder inhaler with 30 blisters. 1 inhalation a day for 24 weeks.

Umeclidinium/Vilanterol 62.5/25 mcgs. Dry powder inhaler with 30 blisters. 1 inhalation a day for 24 weeks.
Drug: Fluticasone Furoate/Vilanterol 100/25 mcgs
Dry powder inhaler with 30 blisters. 100/25mcgs a day for 24 weeks.
Other Names:
  • Relvare
Drug: Umeclidinium/Vilanterol 62.5/25 mcgs
Dry powder inhaler with 30 blisters. 62.5/25mcgs a day for 24 weeks
Other Names:
  • Anoro
Active Comparator: Tobacco Smoke COPD

Fluticasone Furoate/Vilanterol 100/25 mcgs. Dry powder inhaler with 30 blisters. 1 inhalation a day for 24 weeks.

Umeclidinium/Vilanterol 62.5/25 mcgs. Dry powder inhaler with 30 blisters. 1 inhalation a day for 24 weeks.
Drug: Fluticasone Furoate/Vilanterol 100/25 mcgs
Dry powder inhaler with 30 blisters. 100/25mcgs a day for 24 weeks.
Other Names:
  • Relvare
Drug: Umeclidinium/Vilanterol 62.5/25 mcgs
Dry powder inhaler with 30 blisters. 62.5/25mcgs a day for 24 weeks
Other Names:
  • Anoro

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Exacerbations rate
Time Frame: baseline to 24 weeks
moderate and severe exacerbations rate
baseline to 24 weeks
Exacerbations free interval
Time Frame: Baseline to first exacerbation
Exacerbations free interval
Baseline to first exacerbation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pulmonary function change
Time Frame: Change from Baseline at 4, 12 and 24 weeks
Spirometry (FVC and FEV1) and inspiratory capacity
Change from Baseline at 4, 12 and 24 weeks
Impulse oscillometry resistance change
Time Frame: Change from baseline at 24 weeks
R5, R20, DR5R20, Ax (percentage of expected in all values)
Change from baseline at 24 weeks
FeNO change
Time Frame: change from Baseline at 24 weeks
ppb
change from Baseline at 24 weeks
Quality of life change
Time Frame: change from Baseline at 4, 12 and 24 weeks
CAT
change from Baseline at 4, 12 and 24 weeks
Dyspnea change
Time Frame: Change from Baseline at 4, 12 and 24 weeks
mMRC
Change from Baseline at 4, 12 and 24 weeks
Functional capacity change
Time Frame: Change from Baseline at 4, 12 and 24 weeks
6 minute walk test distance
Change from Baseline at 4, 12 and 24 weeks
SGRQ Quality of life change
Time Frame: Change from Baseline at 4, 12 and 24 weeks
SGRQ
Change from Baseline at 4, 12 and 24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Respiratory Diseases, Mexico

Investigators

  • Principal Investigator: Alejandra Ramírez-Venegas, M.S., National Institute of Respiratory Diseases

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 19, 2017

Primary Completion (Actual)

November 19, 2020

Study Completion (Actual)

February 1, 2021

Study Registration Dates

First Submitted

April 5, 2022

First Submitted That Met QC Criteria

April 18, 2022

First Posted (Actual)

April 22, 2022

Study Record Updates

Last Update Posted (Actual)

April 22, 2022

Last Update Submitted That Met QC Criteria

April 18, 2022

Last Verified

April 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • C49-17

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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