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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02867761
Recruitment Status : Completed
First Posted : August 16, 2016
Results First Posted : August 30, 2022
Last Update Posted : August 30, 2022
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
MeiLan Han, University of Michigan

Brief 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.

Condition or disease Intervention/treatment Phase
COPD (Chronic Obstructive Pulmonary Disease) Drug: Indacaterol/Glycopyrrolate Drug: Placebo Phase 3

Detailed 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 780 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: RETHINC: REdefining THerapy In Early COPD for the Pulmonary Trials Cooperative
Actual Study Start Date : August 29, 2017
Actual Primary Completion Date : July 7, 2021
Actual Study Completion Date : July 7, 2021


Arm Intervention/treatment
Active Comparator: Indacaterol/Glycopyrrolate
indacaterol/glycopyrrolate 27.5/15.6 mcg inhaled twice daily for 12 weeks
Drug: Indacaterol/Glycopyrrolate
27.5/15.6 mcg active indacaterol/glycopyrrolate

Placebo Comparator: Placebo
Placebo 27.5/15.6 mcg inhaled twice daily for 12 weeks
Drug: Placebo
27.5/15.6 mcg placebo




Primary Outcome Measures :
  1. 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 [ Time Frame: Baseline and 12 weeks ]

    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).



Secondary Outcome Measures :
  1. Proportion of Individuals With a 2 Unit Improvement in CAT Without Treatment Failure [ Time Frame: 12 weeks ]
    Proportion of individuals with a 2 unit improvement in CAT without treatment failure

  2. Proportion of Individuals With a 1 Unit Improvement in the BDI/TDI Without Treatment Failure [ Time Frame: 12 weeks ]
    Proportion of individuals with a 1 unit improvement in the BDI/TDI without treatment failure

  3. Proportion of Individuals With Both a 4 Unit Improvement in SGRQ and a 1 Unit Improvement in BDI/TDI Without Treatment Failure [ Time Frame: 12 weeks ]
    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).

  4. Mean Change in St. George's Respiratory Questionnaire (SGRQ) [ Time Frame: Baseline, 12 weeks ]
    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).

  5. Mean Change in COPD Assessment Test (CAT) [ Time Frame: Baseline, 12 weeks ]
    Value at 12 Weeks Minus Baseline. 0 - 40; 0 as low symptoms (feeling better) and 40 as high symptoms (feeling worse).

  6. Mean Change in Baseline Dyspnea Index (BDI)/Transition Dyspnea Index (TDI) [ Time Frame: 12 Weeks ]
    Value at 12 Weeks Minus Baseline.

  7. Area Under the Curve (AUC) 0-3 Hours for FEV1 [ Time Frame: At 12 weeks, FEV1 is measured at 1-hour intervals for 3 hours ]
    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.

  8. Change From Baseline in Trough Forced Expiratory Volume Per 1 Second (FEV1) - Absolute Value [ Time Frame: Baseline to 12 Weeks ]
    Trough FEV1 at 12 week minus trough FEV1 at baseline.

  9. Change From Baseline in 12 Hour Trough Inspiratory Capacity - Absolute Value [ Time Frame: Baseline ]
    Change from baseline in 12 hour trough inspiratory capacity - absolute value

  10. Symptoms and Rescue Medication Use Based on Daily Diary [ Time Frame: During study follow-up (Baseline to 12 weeks) ]
    Percentage of days with symptoms (shortness of breath, chest tightness, wheezing, cough, or sputum) or use of albuterol

  11. Treatment Failure Defined by Increase in Lower Respiratory Symptoms Necessitating Treatment With Active, Long-acting Inhaled Bronchodilator, Corticosteroids or Antibiotics [ Time Frame: During study follow-up (baseline to 12 Weeks) ]
    Treatment failure defined by increase in lower respiratory symptoms necessitating treatment with active, long-acting inhaled bronchodilator, corticosteroids or antibiotics

  12. Change From Baseline in Trough FEV1 - % Predicted [ Time Frame: Baseline to 12 Weeks ]
    Trough FEV1 at 12 week minus trough FEV1 at baseline.

  13. Change in FEF25-75% [ Time Frame: Baseline to 12 weeks ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02867761


Locations
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United States, Alabama
Universityof Alabama
Birmingham, Alabama, United States, 35294
United States, California
University of California
Los Angeles, California, United States, 90095
University of California
San Francisco, California, United States, 94143
LABIOMED at Harbor-UCLA Medical Center
Torrance, California, United States, 90502
United States, Illinois
University of Illinois
Chicago, Illinois, United States, 60608
Northwestern University
Chicago, Illinois, United States, 60657
United States, Iowa
University of Iowa
Iowa City, Iowa, United States, 52242
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21224
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
United States, Minnesota
Minneapolis VA Medical Center
Minneapolis, Minnesota, United States, 55417
Minnesota Health partners
Saint Paul, Minnesota, United States, 55130
United States, New York
Cornell University
New York, New York, United States, 10021
United States, North Carolina
Duke University
Durham, North Carolina, United States, 27705
United States, Pennsylvania
Temple University
Philadelphia, Pennsylvania, United States, 19140
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84132
Sponsors and Collaborators
University of Michigan
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
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Principal Investigator: MeiLan Han, MD, MS University of Michigan
Principal Investigator: Prescott Woodruff, MD, MPH University of California, San Francisco
  Study Documents (Full-Text)

Documents provided by MeiLan Han, University of Michigan:
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: MeiLan Han, Professor, Department of Internal Medicine, University of Michigan
ClinicalTrials.gov Identifier: NCT02867761    
Other Study ID Numbers: 1U01HL128952-01 ( U.S. NIH Grant/Contract )
1U01HL128952 ( U.S. NIH Grant/Contract )
First Posted: August 16, 2016    Key Record Dates
Results First Posted: August 30, 2022
Last Update Posted: August 30, 2022
Last Verified: August 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by MeiLan Han, University of Michigan:
COPD
Chronic Obstructive Pulmonary Disease
Pulmonary Function Tests
Current Smoker
Former Smoker
Chronic Obstructive Airway Disease
Respiratory Symptoms
Additional relevant MeSH terms:
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Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases
Glycopyrrolate
Adjuvants, Anesthesia
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs