Clinical trial NCT02696564: Losartan Effects on Emphysema Progression
Official title: Losartan Effects on Emphysema Progression
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Emphysema
Keywords: COPD
emphysema
HRCT
losartan
Lead sponsor: JHSPH Center for Clinical Trials
Sponsor class: OTHER
Collaborators: name: University of Pittsburgh
First posted: 2016-03-02
Enrollment: 220
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change in Mean pct950
timeFrame: 48 weeks
Secondary outcomes:
measure: Change From Baseline in Pre-bronchodilator FEV1 Percent Predicted
timeFrame: 48 weeks
measure: Change From Baseline in Post-bronchodilator FEV1 Percent Predicted
timeFrame: 48 weeks
measure: Change From Baseline in CAT Score
timeFrame: 48 weeks
measure: Change From Baseline in SGRQ Score: Total
timeFrame: 48 weeks
measure: Change From Baseline in SGRQ Score: Symptoms
timeFrame: 48 weeks
measure: Change From Baseline in SGRQ Score: Activity
timeFrame: 48 weeks
measure: Change in SGRQ Score: Impact
timeFrame: 48 weeks
measure: Change From Baseline in mMRC Dyspnea Scale
timeFrame: 48 weeks
measure: Change From Baseline in PROMIS-20a T-score
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: San Diego
country: United States
facility: University of California at San Diego
state: California
city: San Francisco
country: United States
facility: University of California at San Francisco
state: California
city: Denver
country: United States
facility: National Jewish Medical and Research Center
state: Colorado
city: Danbury
country: United States
facility: Western Connecticut Health Network
state: Connecticut
city: Jacksonville
country: United States
facility: University of Florida College of Medicine
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Hospitals
state: Illinois
city: Indianapolis
country: United States
facility: St. Vincent Hospital and Health Care Center, Inc.
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: New Orleans
country: United States
facility: Louisiana State University
state: Louisiana
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Saint Louis
country: United States
facility: St. Louis University School of Medicine
state: Missouri
city: Saint Louis
country: United States
facility: St. Louis Asthma Clinical Research Center - Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: New York University School of Medicine
state: New York
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
city: New York
country: United States
facility: Mount Sinai National Jewish Health Respiratory Institute; Icahn School of Medicine
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Philadelphia
country: United States
facility: Temple University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Colchester
country: United States
facility: Vermont Lung Center at The University of Vermont
state: Vermont
city: Seattle
country: United States
facility: Pacific Northwest Airways - VA Puget Sound Healthcare System
state: Washington
Study officials:
affiliation: Johns Hopkins University
name: Robert Wise, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Johns Hopkins University Bloomberg School of Public Health
name: Janet Holbrook, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.