Alvimopan accelerates gastrointestinal recovery after radical cystectomy: A multicenter randomized placebo-controlled trial

Background Radical cystectomy (RC) for bladder cancer is frequently associated with delayed gastrointestinal (GI) recovery that prolongs hospital length of stay (LOS). Objective To assess the efficacy of alvimopan to accelerate GI recovery after RC. Design, setting, and participants We conducted a randomized double-blind placebo-controlled trial in patients undergoing RC and receiving postoperative intravenous patient-controlled opioid analgesics. Intervention Oral alvimopan 12 mg (maximum: 15 inpatient doses) versus placebo. Outcome measurements and statistical analysis The two-component primary end point was time to upper (first tolerance of solid food) and lower (first bowel movement) GI recovery (GI-2). Time to discharge order written, postoperative LOS, postoperative ileus (POI)-related morbidity, opioid consumption, and adverse events (AEs) were evaluated. An independent adjudication of cardiovascular AEs was performed. Results and limitations Patients were randomized to alvimopan (n = 143) or placebo (n = 137); 277 patients were included in the modified intention-to-treat population. The alvimopan cohort experienced quicker GI-2 recovery (5.5 vs 6.8 d; hazard ratio: 1.8; p < 0.0001), shorter mean LOS (7.4 vs 10.1 d; p = 0.0051), and fewer episodes of POI-related morbidity (8.4% vs 29.1%; p < 0.001). The incidence of opioid consumption and AEs or serious AEs (SAEs) was comparable except for POI, which was lower in the alvimopan group (AEs: 7% vs 26%; SAEs: 5% vs 20%, respectively). Cardiovascular AEs occurred in 8.4% (alvimopan) and 15.3% (placebo) of patients (p = 0.09). Generalizability may be limited due to the exclusion of epidural analgesia and the inclusion of mostly high-volume centers utilizing open laparotomy. Conclusions Alvimopan is a useful addition to a standardized care pathway in patients undergoing RC by accelerating GI recovery and shortening LOS, with a safety profile similar to placebo. Patient summary This study examined the effects of alvimopan on bowel recovery in patients undergoing radical cystectomy for bladder cancer. Patients receiving alvimopan experienced quicker bowel recovery and had a shorter hospital stay compared with those who received placebo, with comparable safety. Trial registration ClinicalTrials.gov identifier NCT00708201