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

NCT02867761 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: 1U01HL128952-011U01HL128952
• Study Type: interventional
• Target: 780
• Locations: 1 country
• Sites: 16

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.

Conditions

COPD (Chronic Obstructive Pulmonary Disease)

Keywords

COPD; Chronic Obstructive Pulmonary Disease; Pulmonary Function Tests; Current Smoker; Former Smoker; Chronic Obstructive Airway Disease; Respiratory Symptoms

Outcome Measures

Primary Outcomes (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

  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 Outcomes (13)

• Proportion of Individuals With a 2 Unit Improvement in CAT Without Treatment Failure

  12 weeks

• Proportion of Individuals With a 1 Unit Improvement in the BDI/TDI Without Treatment Failure

  12 weeks

• Proportion of Individuals With Both a 4 Unit Improvement in SGRQ and a 1 Unit Improvement in BDI/TDI Without Treatment Failure

  12 weeks

• Mean Change in St. George's Respiratory Questionnaire (SGRQ)

  Baseline, 12 weeks

• Mean Change in COPD Assessment Test (CAT)

  Baseline, 12 weeks

Study Arms (2)

Indacaterol/Glycopyrrolate

ACTIVE COMPARATOR

indacaterol/glycopyrrolate 27.5/15.6 mcg inhaled twice daily for 12 weeks

Drug: Indacaterol/Glycopyrrolate

Placebo

PLACEBO COMPARATOR

Placebo 27.5/15.6 mcg inhaled twice daily for 12 weeks

Drug: Placebo

Interventions

Indacaterol/Glycopyrrolate DRUG

27.5/15.6 mcg active indacaterol/glycopyrrolate

Indacaterol/Glycopyrrolate

Placebo DRUG

27.5/15.6 mcg placebo

Placebo

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject must be able to understand and provide informed consent
• Age 40-80
• ≥10 pack-year smoking history
• Post-bronchodilator FEV1/FVC ratio ≥0.70
• Baseline CAT≥10

You may not qualify if:

• Inability or unwillingness of a participant to give written informed consent or comply with study protocol.
• Subject is pregnant, breast-feeding, or plans to become pregnant.
• Active pulmonary infection or prior pulmonary infection where antibiotic and/or steroid treatment was completed ≤4 weeks prior to enrollment.
• Post-BD FVC \< 70% predicted
• A primary diagnosis of asthma established by each study investigator based on ATS/ERS criteria as previously implemented in the MACRO clinical trial.
• Known concomitant lung disease, pulmonary tuberculosis (unless confirmed by chest x-ray to be no longer active), or clinically significant bronchiectasis.
• History (or family history) of long QT syndrome.
• Patients with BMI \< 15 or more than 40 kg/m2.
• Patients with diabetes Type I or uncontrolled diabetes Type II.
• 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.
• Patients with any history of lung cancer.
• 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.
• 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.
• 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.
• Patients unable to successfully use a dry powder inhaler device or perform spirometry measurements.

Sponsors & Collaborators

• University of Michigan: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (16)

Universityof Alabama

Birmingham, Alabama, 35294, United States

Location

University of California

Los Angeles, California, 90095, United States

Location

University of California

San Francisco, California, 94143, United States

Location

LABIOMED at Harbor-UCLA Medical Center

Torrance, California, 90502, United States

Location

University of Illinois

Chicago, Illinois, 60608, United States

Location

Northwestern University

Chicago, Illinois, 60657, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21224, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Minneapolis VA Medical Center

Minneapolis, Minnesota, 55417, United States

Location

Minnesota Health partners

Saint Paul, Minnesota, 55130, United States

Location

Cornell University

New York, New York, 10021, United States

Location

Duke University

Durham, North Carolina, 27705, United States

Location

Temple University

Philadelphia, Pennsylvania, 19140, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Related Publications (1)

• Han MK, Ye W, Wang D, White E, Arjomandi M, Barjaktarevic IZ, Brown SA, Buhr RG, Comellas AP, Cooper CB, Criner GJ, Dransfield MT, Drescher F, Folz RJ, Hansel NN, Kalhan R, Kaner RJ, Kanner RE, Krishnan JA, Lazarus SC, Maddipati V, Martinez FJ, Mathews A, Meldrum C, McEvoy C, Nyunoya T, Rogers L, Stringer WW, Wendt CH, Wise RA, Wisniewski SR, Sciurba FC, Woodruff PG; RETHINC Study Group. Bronchodilators in Tobacco-Exposed Persons with Symptoms and Preserved Lung Function. N Engl J Med. 2022 Sep 29;387(13):1173-1184. doi: 10.1056/NEJMoa2204752. Epub 2022 Sep 4.

  PMID: 36066078 DERIVED

Related Links

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

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Smoking Cessation; Signs and Symptoms, Respiratory

Interventions

indacaterol; Glycopyrrolate

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Health Behavior; Behavior; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Quaternary Ammonium Compounds; Amines; Organic Chemicals; Onium Compounds; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Meilan K. Han
• Organization: University of Michigan

mrking@med.umich.edu

734 615-9772

Study Officials

• MeiLan Han, MD, MS

  University of Michigan

  PRINCIPAL INVESTIGATOR

• Prescott Woodruff, MD, MPH

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Department of Internal Medicine

Study Record Dates

• First Submitted: August 12, 2016
• First Posted: August 16, 2016
• Study Start: August 29, 2017
• Primary Completion: July 7, 2021
• Study Completion: July 7, 2021
• Last Updated: April 13, 2023
• Results First Posted: August 30, 2022

Record last verified: 2023-04

Locations

US (16)