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Losartan Effects on Emphysema Progression (LEEP)

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ClinicalTrials.gov Identifier: NCT02696564
Recruitment Status : Completed
First Posted : March 2, 2016
Results First Posted : June 1, 2022
Last Update Posted : June 1, 2022
Sponsor:
Collaborator:
University of Pittsburgh
Information provided by (Responsible Party):
JHSPH Center for Clinical Trials

Tracking Information
First Submitted Date  ICMJE February 25, 2016
First Posted Date  ICMJE March 2, 2016
Results First Submitted Date  ICMJE March 24, 2022
Results First Posted Date  ICMJE June 1, 2022
Last Update Posted Date June 1, 2022
Actual Study Start Date  ICMJE May 23, 2017
Actual Primary Completion Date March 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 24, 2022)
Change in Mean pct950 [ Time Frame: 48 weeks ]
change in percentage of voxels with density less than -950 Hounsfield Units
Original Primary Outcome Measures  ICMJE
 (submitted: February 25, 2016)
change in mean pct950 [ Time Frame: 48 weeks ]
change in percentage of voxels with density less than -950 Hounsfield Units
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 4, 2022)
  • Change From Baseline in Pre-bronchodilator FEV1 Percent Predicted [ Time Frame: 48 weeks ]
    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 [ Time Frame: 48 weeks ]
    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 [ Time Frame: 48 weeks ]
    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 [ Time Frame: 48 weeks ]
    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 [ Time Frame: 48 weeks ]
    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 [ Time Frame: 48 weeks ]
    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 [ Time Frame: 48 weeks ]
    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 [ Time Frame: 48 weeks ]
    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 [ Time Frame: 48 weeks ]
    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)
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Losartan Effects on Emphysema Progression
Official Title  ICMJE Losartan Effects on Emphysema Progression
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Emphysema
Intervention  ICMJE
  • Drug: Losartan
    50mg once per day for two weeks,followed by 100mg once per day for 46 weeks if increased dose tolerated
  • Drug: Placebo
    one capsule per day for two weeks, followed by two capsules per day for 46 weeks
Study Arms  ICMJE
  • Active Comparator: 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.
    Intervention: Drug: Losartan
  • Placebo Comparator: 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.
    Intervention: Drug: Placebo
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 25, 2016)
220
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE June 30, 2021
Actual Primary Completion Date March 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 40 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02696564
Other Study ID Numbers  ICMJE U01HL128951( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: NHLBI Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC)
Current Responsible Party JHSPH Center for Clinical Trials
Original Responsible Party Robert A. Wise, Johns Hopkins University, Professor of Medicine
Current Study Sponsor  ICMJE JHSPH Center for Clinical Trials
Original Study Sponsor  ICMJE Johns Hopkins University
Collaborators  ICMJE University of Pittsburgh
Investigators  ICMJE
Principal Investigator: Robert Wise, MD Johns Hopkins University
Principal Investigator: Janet Holbrook, PhD Johns Hopkins University Bloomberg School of Public Health
PRS Account JHSPH Center for Clinical Trials
Verification Date May 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP