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Losartan Effects on Emphysema Progression (LEEP)

Primary Purpose

Emphysema

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Losartan

Placebo

About this trial

This is an interventional treatment trial for Emphysema focused on measuring COPD, emphysema, HRCT, losartan

Eligibility Criteria

40 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

University of Alabama at Birmingham
University of Arizona
University of California at San Diego
University of California at San Francisco
National Jewish Medical and Research Center
Western Connecticut Health Network
University of Florida College of Medicine
University of South Florida
University of Illinois at Chicago
Northwestern University
Rush University Medical Center
University of Chicago Hospitals
St. Vincent Hospital and Health Care Center, Inc.
University of Kansas Medical Center
Louisiana State University
University of Michigan
St. Louis University School of Medicine
St. Louis Asthma Clinical Research Center - Washington University School of Medicine
New York University School of Medicine
Weill Cornell Medicine
Mount Sinai National Jewish Health Respiratory Institute; Icahn School of Medicine
Columbia University Medical Center
Duke University Medical Center
Temple University
University of Pittsburgh Medical Center
Baylor College of Medicine
Vermont Lung Center at The University of Vermont
Pacific Northwest Airways - VA Puget Sound Healthcare System

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Losartan

placebo

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Change in Mean pct950

change in percentage of voxels with density less than -950 Hounsfield Units

Secondary Outcome Measures

Change From Baseline in Pre-bronchodilator FEV1 Percent Predicted

Change from the first visit to the final visit in a spirometry (breathing test) measure: forced expiratory volume in one second (FEV1). The test is administered without the participant taking any bronchodilator medication. The FEV1 is compared to standard predicted values in the US population for each individual based on their height, gender, and ethnic group; the result is given as percent of predicted value.

Change From Baseline in Post-bronchodilator FEV1 Percent Predicted

Change from the first visit to the final visit in a spirometry (breathing test) measure: forced expiratory volume in one second (FEV1). This test is performed after the participant is given bronchodilator medications. The FEV1 is compared to standard predicted values in the US population for each individual based on their height, gender, and ethnic group; the result is given as percent of predicted value.

Change From Baseline in CAT Score

Change from the first visit to the final visit in the participant's COPD Assessment Test (CAT) score. The CAT is an 8-item questionnaire assessing the impact of COPD on health status. CAT scores range from 0 to 40, with higher scores indicating a more severe impact of COPD on a patient's life.

Change From Baseline in SGRQ Score: Total

Change from the first visit to the final visit in participants' score on the St George's Respiratory Questionnaire - COPD. The St George's Respiratory Questionnaire for COPD patients (SGRQ-C) is a 40-item questionnaire designed to measure impact on overall health, daily life, and perceived well-being in patients with COPD. The SGRQ-C includes three categories: Symptoms (frequency and severity), Activities caused or limited by breathlessness, and Impacts on social and psychological functioning caused by airways disease. The total score and scores for each category range from 0 to 100, with higher scores indicating more limitations.

Change From Baseline in SGRQ Score: Symptoms

Change from the first visit to the final visit in participants' scores on the symptom-related questions on the St Georges Respiratory Questionnaire-COPD. The St George's Respiratory Questionnaire for COPD patients (SGRQ-C) is a 40-item questionnaire designed to measure impact on overall health, daily life, and perceived well-being in patients with COPD. The SGRQ-C includes three categories: Symptoms (frequency and severity), Activities caused or limited by breathlessness, and Impacts on social and psychological functioning caused by airways disease. The total score and scores for each category range from 0 to 100, with higher scores indicating more limitations.

Change From Baseline in SGRQ Score: Activity

Change from the first visit to the final visit in participants' scores on the activity-related questions on the St Georges Respiratory Questionnaire-COPD. The St George's Respiratory Questionnaire for COPD patients (SGRQ-C) is a 40-item questionnaire designed to measure impact on overall health, daily life, and perceived well-being in patients with COPD. The SGRQ-C includes three categories: Symptoms (frequency and severity), Activities caused or limited by breathlessness, and Impacts on social and psychological functioning caused by airways disease. The total score and scores for each category range from 0 to 100, with higher scores indicating more limitations.

Change in SGRQ Score: Impact

Change from the first visit to the final visit in participants' scores on the impact-related questions on the St Georges Respiratory Questionnaire-COPD. The St George's Respiratory Questionnaire for COPD patients (SGRQ-C) is a 40-item questionnaire designed to measure impact on overall health, daily life, and perceived well-being in patients with COPD. The SGRQ-C includes three categories: Symptoms (frequency and severity), Activities caused or limited by breathlessness, and Impacts on social and psychological functioning caused by airways disease. The total score and scores for each category range from 0 to 100, with higher scores indicating more limitations.

Change From Baseline in mMRC Dyspnea Scale

Change from the first visit to the final visit in participants' scores on the modified Medical Research Council dyspnea scale. The modified Medical Research Council dyspnea scale (mMRC) is a self-rating tool to measure how much breathlessness affects someone's day to day activities. Scores are between 0 and 4, with higher scores indicating more severe breathlessness.

Change From Baseline in PROMIS-20a T-score

Change from the first visit to the final visit in participants' scores on the Patient-Reported Outcome Measures Information System (PROMIS) Physical Function assessment. The Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function Short Form 20a is a 20-item questionnaire used to indicate a patient's ability to perform activities of daily living, such as bathing, dressing, and commuting. Raw scores from this questionnaire are compared to a reference population to create a "T-score". The general US population is the reference population. In this T-score metric, 50 indicates the population mean with a standard deviation of 10. Higher scores mean better outcomes (more ability to do activities of daily living)

Full Information

NCT ID

NCT02696564

First Posted

February 25, 2016

Last Updated

May 4, 2022

Sponsor

JHSPH Center for Clinical Trials

Collaborators

University of Pittsburgh

1. Study Identification

Unique Protocol Identification Number

NCT02696564

Brief Title

Losartan Effects on Emphysema Progression

Acronym

LEEP

Official Title

Losartan Effects on Emphysema Progression

Study Type

Interventional

2. Study Status

Record Verification Date

May 2022

Overall Recruitment Status

Completed

Study Start Date

May 23, 2017 (Actual)

Primary Completion Date

March 31, 2021 (Actual)

Study Completion Date

June 30, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

JHSPH Center for Clinical Trials

Collaborators

University of Pittsburgh

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Emphysema

Keywords

COPD, emphysema, HRCT, losartan

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

220 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Losartan

Arm Type

Active Comparator

Arm Description

Arm Title

placebo

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Losartan

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

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

Primary Outcome Measure Information:

Title

Change in Mean pct950

Description

change in percentage of voxels with density less than -950 Hounsfield Units

Time Frame

48 weeks

Secondary Outcome Measure Information:

Title

Change From Baseline in Pre-bronchodilator FEV1 Percent Predicted

Description

Time Frame

48 weeks

Title

Change From Baseline in Post-bronchodilator FEV1 Percent Predicted

Description

Time Frame

48 weeks

Title

Change From Baseline in CAT Score

Description

Time Frame

48 weeks

Title

Change From Baseline in SGRQ Score: Total

Description

Time Frame

48 weeks

Title

Change From Baseline in SGRQ Score: Symptoms

Description

Time Frame

48 weeks

Title

Change From Baseline in SGRQ Score: Activity

Description

Time Frame

48 weeks

Title

Change in SGRQ Score: Impact

Description

Time Frame

48 weeks

Title

Change From Baseline in mMRC Dyspnea Scale

Description

Time Frame

48 weeks

Title

Change From Baseline in PROMIS-20a T-score

Description

Time Frame

48 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

40 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Robert Wise, MD

Organizational Affiliation

Johns Hopkins University

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Janet Holbrook, PhD

Organizational Affiliation

Johns Hopkins University Bloomberg School of Public Health

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Alabama at Birmingham

City

Birmingham

State/Province

Alabama

ZIP/Postal Code

35249

Country

United States

Facility Name

University of Arizona

City

Tucson

State/Province

Arizona

ZIP/Postal Code

85724

Country

United States

Facility Name

University of California at San Diego

City

San Diego

State/Province

California

ZIP/Postal Code

92103

Country

United States

Facility Name

University of California at San Francisco

City

San Francisco

State/Province

California

ZIP/Postal Code

94143

Country

United States

Facility Name

National Jewish Medical and Research Center

City

Denver

State/Province

Colorado

ZIP/Postal Code

80206

Country

United States

Facility Name

Western Connecticut Health Network

City

Danbury

State/Province

Connecticut

ZIP/Postal Code

06810

Country

United States

Facility Name

University of Florida College of Medicine

City

Jacksonville

State/Province

Florida

ZIP/Postal Code

32209

Country

United States

Facility Name

University of South Florida

City

Tampa

State/Province

Florida

ZIP/Postal Code

33613

Country

United States

Facility Name

University of Illinois at Chicago

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60608

Country

United States

Facility Name

Northwestern University

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60611

Country

United States

Facility Name

Rush University Medical Center

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60612

Country

United States

Facility Name

University of Chicago Hospitals

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60637

Country

United States

Facility Name

St. Vincent Hospital and Health Care Center, Inc.

City

Indianapolis

State/Province

Indiana

ZIP/Postal Code

46260

Country

United States

Facility Name

University of Kansas Medical Center

City

Kansas City

State/Province

Kansas

ZIP/Postal Code

66160

Country

United States

Facility Name

Louisiana State University

City

New Orleans

State/Province

Louisiana

ZIP/Postal Code

70112

Country

United States

Facility Name

University of Michigan

City

Ann Arbor

State/Province

Michigan

ZIP/Postal Code

48109-5360

Country

United States

Facility Name

St. Louis University School of Medicine

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63104

Country

United States

Facility Name

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

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63110

Country

United States

Facility Name

New York University School of Medicine

City

New York

State/Province

New York

ZIP/Postal Code

10016

Country

United States

Facility Name

Weill Cornell Medicine

City

New York

State/Province

New York

ZIP/Postal Code

10021

Country

United States

Facility Name

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

City

New York

State/Province

New York

ZIP/Postal Code

10029

Country

United States

Facility Name

Columbia University Medical Center

City

New York

State/Province

New York

ZIP/Postal Code

10032

Country

United States

Facility Name

Duke University Medical Center

City

Durham

State/Province

North Carolina

ZIP/Postal Code

27710

Country

United States

Facility Name

Temple University

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19140

Country

United States

Facility Name

University of Pittsburgh Medical Center

City

Pittsburgh

State/Province

Pennsylvania

ZIP/Postal Code

15213

Country

United States

Facility Name

Baylor College of Medicine

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Facility Name

Vermont Lung Center at The University of Vermont

City

Colchester

State/Province

Vermont

ZIP/Postal Code

05466

Country

United States

Facility Name

Pacific Northwest Airways - VA Puget Sound Healthcare System

City

Seattle

State/Province

Washington

ZIP/Postal Code

98108

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

NHLBI Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC)

Citations:

PubMed Identifier

35649189

Citation

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.

Results Reference

derived

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Losartan Effects on Emphysema Progression

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