RETHINC: REdefining THerapy In Early COPD for the Pulmonary Trials Cooperative

COPD (Chronic Obstructive Pulmonary Disease) Clinical Trial

— RETHINC  

Official title:

RETHINC: REdefining THerapy In Early COPD for the Pulmonary Trials Cooperative

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02867761
• Other study ID #: 1U01HL128952-01
• Secondary ID: 1U01HL128952
• Status: Completed
• Phase: Phase 3
• Start date: August 29, 2017
• Est. completion date: July 7, 2021

Study information

• Verified date: April 2023
• Source: University of Michigan
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study hypothesis is that symptomatic current and former smokers with spirometric values within the normal range (post-bronchodilator FEV1/FVC≥0.70 and post-BD FVC ≥ 70% predicted will still derive symptomatic benefit from long-acting bronchodilator therapy even though they are excluded from current GOLD guideline recommendations.

Description:

RETHINC is a 12-week multicenter, randomized, double-blind, placebo-controlled, parallel-group study to assess the efficacy and safety of indacaterol/glycopyrrolate 27.5/15.6 mcg inhaled twice daily in symptomatic current and former smokers with respiratory symptoms despite preserved spirometry as defined by CAT ≥ 10 and post-bronchodilator FEV1/FVC ratio ≥0.70, respectively.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 780
• Est. completion date: July 7, 2021
• Est. primary completion date: July 7, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Subject must be able to understand and provide informed consent

2. Age 40-80

3. =10 pack-year smoking history

4. Post-bronchodilator FEV1/FVC ratio =0.70

5. Baseline CAT=10

Exclusion Criteria:

1. Inability or unwillingness of a participant to give written informed consent or comply with study protocol.

2. Subject is pregnant, breast-feeding, or plans to become pregnant.

3. Active pulmonary infection or prior pulmonary infection where antibiotic and/or steroid treatment was completed =4 weeks prior to enrollment.

4. Post-BD FVC < 70% predicted

5. A primary diagnosis of asthma established by each study investigator based on ATS/ERS criteria as previously implemented in the MACRO clinical trial.

6. Known concomitant lung disease, pulmonary tuberculosis (unless confirmed by chest x-ray to be no longer active), or clinically significant bronchiectasis.

7. History (or family history) of long QT syndrome.

8. History of paroxysmal (intermittent) atrial fibrillation will be considered an exclusion. Patients with persistent atrial fibrillation as defined by continuous atrial fibrillation for at least 6 months and controlled with a rate control strategy (i.e., selective beta blocker, calcium channel blocker, pacemaker placement, digoxin or ablation therapy) for at least 6 months may be considered for inclusion. In such patients, heart rate at enrollment must be < 100/min.

9. Patients with BMI < 15 or more than 40 kg/m2.

10. Patients with diabetes Type I or uncontrolled diabetes Type II.

11. Patients who, in the judgment of the investigator, have a clinically relevant laboratory abnormality or a clinically significant condition such as (but not limited to) significant renal disease, psychiatric disease, gastrointestinal disease, unstable ischemic heart disease, arrhythmia (excluding chronic stable atrial fibrillation), uncontrolled hypertension or any other condition which in the opinion of investigator might compromise patient safety or compliance, interfere with evaluation, or preclude completion of the study.

12. Patients with any history of lung cancer.

13. Patients with narrow-angle glaucoma, symptomatic benign prostatic hyperplasia or bladder-neck obstruction or severe renal impairment or urinary retention. Benign Prostatic Hyperplasia (BPH) patients who are stable on treatment can be considered.

14. Any other past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.

15. Patients with a history of hypersensitivity to any of the study drugs or to drugs from similar chemical classification, including untoward reactions to sympathomimetic amines or inhaled medication or any component thereof.

16. Patients unable to successfully use a dry powder inhaler device or perform spirometry measurements.

17. Use of other investigational drugs at the time of enrollment or within 30 days or 5 half-lives of enrollment, whichever is longer.

18. Patients receiving any protocol-specified prohibited medications..

19. Patients receiving any protocol-specified prohibited COPD related medications (will be required to undergo a required washout period prior to enrollment).

Related Conditions & MeSH terms

• COPD (Chronic Obstructive Pulmonary Disease)
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Indacaterol/Glycopyrrolate
27.5/15.6 mcg active indacaterol/glycopyrrolate
• Placebo
27.5/15.6 mcg placebo

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	Johns Hopkins University	Baltimore	Maryland
United States	Universityof Alabama	Birmingham	Alabama
United States	Northwestern University	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
United States	Duke University	Durham	North Carolina
United States	University of Iowa	Iowa City	Iowa
United States	University of California	Los Angeles	California
United States	Minneapolis VA Medical Center	Minneapolis	Minnesota
United States	Cornell University	New York	New York
United States	Temple University	Philadelphia	Pennsylvania
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	Minnesota Health partners	Saint Paul	Minnesota
United States	University of Utah	Salt Lake City	Utah
United States	University of California	San Francisco	California
United States	LABIOMED at Harbor-UCLA Medical Center	Torrance	California

Sponsors (2)

Lead Sponsor	Collaborator
University of Michigan	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion (Percentage) of Individuals Who Experience a 4 Unit Improvement in St. George's Respiratory Questionnaire (SGRQ) at 12 Weeks and do Not Meet Criteria for Treatment Failure During the 12 Week Treatment Period	Measured by units of improvement in SGRQ scores at Baseline and 12 weeks, as well as review of treatment failure status at 4 weeks and 12 weeks of treatment (treatment failure is defined by an increase in lower respiratory symptoms necessitating treatment with active, long-acting inhaled bronchodilator, corticosteroids or antibiotics).; A 4 unit change is the minimum clinically important difference. SGRQ has a 0 - 100 score; 0 as low symptoms (feeling better) and 100 as high symptoms (feeling worse).	Baseline and 12 weeks
Secondary	Proportion of Individuals With a 2 Unit Improvement in CAT Without Treatment Failure	Proportion of individuals with a 2 unit improvement in CAT without treatment failure	12 weeks
Secondary	Proportion of Individuals With a 1 Unit Improvement in the BDI/TDI Without Treatment Failure	Proportion of individuals with a 1 unit improvement in the BDI/TDI without treatment failure	12 weeks
Secondary	Proportion of Individuals With Both a 4 Unit Improvement in SGRQ and a 1 Unit Improvement in BDI/TDI Without Treatment Failure	Measured by units of improvement in SGRQ scores at Baseline and 12 weeks, as well as review of treatment failure status at 4 weeks and 12 weeks of treatment (treatment failure is defined by an increase in lower respiratory symptoms necessitating treatment with active, long-acting inhaled bronchodilator, corticosteroids or antibiotics).	12 weeks
Secondary	Mean Change in St. George's Respiratory Questionnaire (SGRQ)	Value at 12 Weeks Minus Baseline. SGRQ has a 0 - 100 score; 0 as low symptoms (feeling better) and 100 as high symptoms (feeling worse).	Baseline, 12 weeks
Secondary	Mean Change in COPD Assessment Test (CAT)	Value at 12 Weeks Minus Baseline. 0 - 40; 0 as low symptoms (feeling better) and 40 as high symptoms (feeling worse).	Baseline, 12 weeks
Secondary	Mean Change in Baseline Dyspnea Index (BDI)/Transition Dyspnea Index (TDI)	Value at 12 Weeks Minus Baseline.	12 Weeks
Secondary	Area Under the Curve (AUC) 0-3 Hours for FEV1	FEV1 AUC0-3h was calculated as the area under the FEV1-time curve from 0 to 3h post-dose using the trapezoidal rule, divided by the duration (3h) to report in liters.	At 12 weeks, FEV1 is measured at 1-hour intervals for 3 hours
Secondary	Change From Baseline in Trough Forced Expiratory Volume Per 1 Second (FEV1) - Absolute Value	Trough FEV1 at 12 week minus trough FEV1 at baseline.	Baseline to 12 Weeks
Secondary	Change From Baseline in 12 Hour Trough Inspiratory Capacity - Absolute Value	Change from baseline in 12 hour trough inspiratory capacity - absolute value	Baseline
Secondary	Symptoms and Rescue Medication Use Based on Daily Diary	Percentage of days with symptoms (shortness of breath, chest tightness, wheezing, cough, or sputum) or use of albuterol	During study follow-up (Baseline to 12 weeks)
Secondary	Treatment Failure Defined by Increase in Lower Respiratory Symptoms Necessitating Treatment With Active, Long-acting Inhaled Bronchodilator, Corticosteroids or Antibiotics	Treatment failure defined by increase in lower respiratory symptoms necessitating treatment with active, long-acting inhaled bronchodilator, corticosteroids or antibiotics	During study follow-up (baseline to 12 Weeks)
Secondary	Change From Baseline in Trough FEV1 - % Predicted	Trough FEV1 at 12 week minus trough FEV1 at baseline.	Baseline to 12 Weeks
Secondary	Change in FEF25-75%	FEF25-75%-Forced expiratory flow over the middle one half of the FVC; the average flow from the point at which 25 percent of the FVC has been exhaled to the point at which 75 percent of the FVC has been exhaled.	Baseline to 12 weeks

External Links

•   Pulmonary Trials Cooperative website, containing information regarding RETHINC and other studies included in the Pulmonary Trials Cooperative