Losartan Effects on Emphysema Progression Randomized Clinical Trial: Rationale, Design, Recruitment, and Retention.

ABSTRACT

The Losartan Effects on Emphysema Progression (LEEP) trial was designed to test the hypothesis that losartan slows progression of emphysema in chronic obstructive pulmonary disease (COPD) patients (NCT00720226). It was conducted by the Pulmonary Trials Cooperative consortium, in collaboration with the American Lung Association Airways Clinical Research Centers network. We describe the design of the trial and challenges for recruitment and follow-up of participants. LEEP is a placebo-controlled, parallel randomized trial, allocation ratio of 11, with a planned sample size of 220. Primary eligibility criteria were mild emphysema based on high-resolution computed tomography (HRCT) scans with 5% to 35% voxels <-950 Hounsfield units (HU), airway obstruction based on spirometry, and not taking an angiotensin receptor blocker or angiotensin converting enzyme (ACE) inhibitor. Participants received either losartan or placebo for 48 weeks. A total of 2779 individuals were screened to enroll 220 eligible participants at 26 clinical sites, all located in the continental United States. Recruitment took 45% longer than planned (32 months versus 22 months), with an average accrual rate of 6.7 participants per month. Recruitment challenges included identification of eligible participants who were not already taking or who did not have an established clinical indication for an angiotensin receptor blocker or ACE inhibitor drug and recalls of contaminated lots of losartan by the Food and Drug Administration. A number of recruitment initiatives were launched in response. Recruitment was completed in February 2020, just prior to a nationwide shutdown of research activities due to the coronavirus disease 2019 (COVID-19) pandemic.