Losartan Effects on Emphysema Progression

NCT ID: NCT02696564

Last Updated: 2022-06-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 220 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-05-23
• Study Completion Date: 2021-06-30

Brief Summary

A randomized, parallel, placebo controlled trial to evaluate the effect of 100mg/day losartan on the progression of emphysema as measured by quantitative HRCT compared to placebo

.

Detailed Description

This is a trial designed to test if a treatment, losartan, may decrease the progression of Chronic Obstructive Pulmonary Disease (COPD). Losartan is an angiotensin receptor blocking agent, commonly used as an antihypertensive agent, which has been shown to alter cardiac remodeling after myocardial infarction and renovascular remodeling in diabetes-mellitus. In this trial participants with mild to severe COPD, with Computed Tomography (CT) evidence of emphysema (5-35% of voxels with < -950 Hounsfield Units), will be randomly assigned to receive 100mg/day of losartan or placebo for 48 weeks. The primary outcome measure will be the rate of progression of emphysema, quantified as the percent of lung voxels with a density less than -950 HU as measured by High Resolution CT (HRCT, from baseline to 48 weeks.

Conditions

Emphysema

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Losartan

At randomization participants will start with a dose of 50mg (one capsule) once a day for 2 weeks. If this dose is well tolerated and systolic BP is \>90 mm Hg and diastolic BP is \> 60 mm Hg, the dose will be increased to 100 mg (2 capsules) once a day for the remaining 46 weeks.

Group Type: ACTIVE_COMPARATOR

Losartan

Intervention Type: DRUG

50mg once per day for two weeks,followed by 100mg once per day for 46 weeks if increased dose tolerated

placebo

At randomization participants will start with a dose of one capsule (inactive) once a day for 2 weeks. After two weeks, if systolic BP is \>90 mm Hg and diastolic BP is \> 60 mm Hg, the dose will be increased to 2 capsules once a day for the remaining 46 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

one capsule per day for two weeks, followed by two capsules per day for 46 weeks

Interventions

Losartan

50mg once per day for two weeks,followed by 100mg once per day for 46 weeks if increased dose tolerated

Intervention Type: DRUG

Placebo

one capsule per day for two weeks, followed by two capsules per day for 46 weeks

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Mild to severe COPD: Ratio of forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) less than or equal to 0.70, FEV1 20-80% of predicted
• Current or former smoker
• HRCT scan with 5-35% of voxels with density less than -950 Hounsfield Units (HU)
• Ability to understand and willingness to sign consent documents

Exclusion Criteria

• Current therapy with angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)
• Known intolerance to ACE inhibitor or ARB
• History of angioedema
• Conventional indication for ACE inhibitor or ARB (e.g., history of myocardial infarction, known cardiomyopathy)
• Renal insufficiency (GFR <30 mL/min by Cockcroft-Gault calculation)
• Current regular use of NSAIDs defined as daily use 5 or more days of the week for more than one month
• Potassium supplementation or serum potassium level of 5.0 milliequivalents (mEq)/dL or higher at V1
• Current use of a potassium sparing diuretic
• COPD exacerbation requiring treatment within 6 weeks at V1
• Chronic systemic corticosteroid use of more than 10mg/day of prednisone
• Resting SpO2 <89% on 2 L nasal cannula continuous flow; unless at altitude > 4,000 feet, then resting oxygen saturation (SpO2) <89% on 4 L N C continuous flow
• Untreated arterial hypertension (systolic blood pressure greater than140 mm Hg, diastolic blood pressure greater than 90 mm Hg)
• Blood pressure less than 90 mm Hg systolic or 60 mm Hg diastolic while standing or sitting
• Known unilateral or bilateral renal artery stenosis higher than 70%
• Previous lung resection surgery
• Evidence of interstitial, occupational or chronic infectious lung disease
• Changes to chest that preclude adequate HRCT imaging (e.g. Metallic objects in the chest such as shrapnel or pacemaker leads)
• For women of child bearing potential, positive pregnancy test or unwillingness to use two methods of birth control or abstinence for the duration of the study
• Major chronic illnesses which in the judgment of the study physician would interfere with participation in the study e.g. including but not limited to: cardiac, renal, hepatic (LFTs more than 2.5x normal upper limit), neurological, psychiatric, endocrine or neoplastic diseases, uncontrolled diabetes, uncontrolled HIV infection or other immune system disorder, hyperthyroidism, seizure disorders, non-skin cancer, rheumatic diseases
• Failure to keep screening appointments or other indicators of non-adherence
• Inability to be contacted by telephone
• Intention to leave area within 12 months

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Pittsburgh

OTHER

Sponsor Role: collaborator

JHSPH Center for Clinical Trials

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Robert Wise, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Janet Holbrook, PhD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University Bloomberg School of Public Health

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

University of Arizona

Tucson, Arizona, United States

University of California at San Diego

San Diego, California, United States

University of California at San Francisco

San Francisco, California, United States

National Jewish Medical and Research Center

Denver, Colorado, United States

Western Connecticut Health Network

Danbury, Connecticut, United States

University of Florida College of Medicine

Jacksonville, Florida, United States

University of South Florida

Tampa, Florida, United States

University of Illinois at Chicago

Chicago, Illinois, United States

Northwestern University

Chicago, Illinois, United States

Rush University Medical Center

Chicago, Illinois, United States

University of Chicago Hospitals

Chicago, Illinois, United States

St. Vincent Hospital and Health Care Center, Inc.

Indianapolis, Indiana, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

Louisiana State University

New Orleans, Louisiana, United States

University of Michigan

Ann Arbor, Michigan, United States

St. Louis University School of Medicine

St Louis, Missouri, United States

St. Louis Asthma Clinical Research Center - Washington University School of Medicine

St Louis, Missouri, United States

New York University School of Medicine

New York, New York, United States

Weill Cornell Medicine

New York, New York, United States

Mount Sinai National Jewish Health Respiratory Institute; Icahn School of Medicine

New York, New York, United States

Columbia University Medical Center

New York, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

Temple University

Philadelphia, Pennsylvania, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Baylor College of Medicine

Houston, Texas, United States

Vermont Lung Center at The University of Vermont

Colchester, Vermont, United States

Pacific Northwest Airways - VA Puget Sound Healthcare System

Seattle, Washington, United States

Countries

United States

References

Wise RA, Holbrook JT, Brown RH, Criner GJ, Dransfield MT, He J, Henderson RJ, Kaminsky DA, Kaner RJ, Lazarus SC, Make BJ, McCormack MC, Neptune ER, Que LG. Clinical Trial of Losartan for Pulmonary Emphysema: Pulmonary Trials Cooperative Losartan Effects on Emphysema Progression Clinical Trial. Am J Respir Crit Care Med. 2022 Oct 1;206(7):838-845. doi: 10.1164/rccm.202201-0206OC.

Reference Type: DERIVED

PMID: 35649189 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

U01HL128951

Identifier Type: NIH

Identifier Source: org_study_id

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