Site enrollment rate, outcomes, and study drug effects in a multicenter trial. Results from RELAX-AHF.

BACKGROUND: Site selection is critical in acute heart failure trials. We assessed whether the enrollment rate per site affects patients' characteristics, outcomes and treatment response.

METHODS AND RESULTS: A total of 1161 patients enrolled at 96 sites in the RELAX-AHF trial (serelaxin vs placebo) were included. Annualized enrollment rate was calculated as the total number of patients enrolled at each site divided by time that the site was open (patients per year). Sites were classified in low (<10), medium (10-20) and high enrolling sites (>20 patients per site/year) and were compared for prognosis and serelaxin effect. High enrolling sites were more prevalent in Eastern Europe and Israel. Time from hospital admission to randomization was shorter in high enrolling sites (6.3±4.4h>20 patients sites versus 8.7±4.5h for <10 patients sites; p<0.0001). Patients had slightly fewer comorbidities, lower levels of natriuretic peptides and creatinine and more severe pulmonary congestion in high enrolling sites. Use of evidence-based therapies was higher in high enrolling sites. The rates of worsening heart failure to day 5, 180-day cardiovascular and all-cause mortality and 60-day heart failure/renal failure rehospitalization or cardiovascular death, were similar across study groups even after adjustment for covariates. The effects of serelaxin on these outcomes did not differ by enrollment rate.

CONCLUSIONS: Characteristics of RELAX-AHF study patients enrolled in high versus low enrolling sites differed only slightly and there were no differences in outcomes. Differences in serelaxin effects by enrollment rate were not discernible.