PMID- 24630419 OWN - NLM STAT- MEDLINE DCOM- 20150707 LR - 20220409 IS - 1873-7560 (Electronic) IS - 0302-2838 (Linking) VI - 66 IP - 2 DP - 2014 Aug TI - Alvimopan accelerates gastrointestinal recovery after radical cystectomy: a multicenter randomized placebo-controlled trial. PG - 265-72 LID - S0302-2838(14)00165-1 [pii] LID - 10.1016/j.eururo.2014.02.036 [doi] AB - 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. CI - Copyright (c) 2014 European Association of Urology. All rights reserved. FAU - Lee, Cheryl T AU - Lee CT AD - University of Michigan, Ann Arbor, MI, USA. Electronic address: ctlee@med.umich.edu. FAU - Chang, Sam S AU - Chang SS AD - Vanderbilt University Medical Center, Nashville, TN, USA. FAU - Kamat, Ashish M AU - Kamat AM AD - The University of Texas MD Anderson Cancer Center, Houston, TX, USA. FAU - Amiel, Gilad AU - Amiel G AD - Baylor University, Baylor College of Medicine, Houston, TX, USA. FAU - Beard, Timothy L AU - Beard TL AD - Bend Memorial Clinic, Bend, OR, USA. FAU - Fergany, Amr AU - Fergany A AD - Cleveland Clinic Foundation, Cleveland, OH, USA. FAU - Karnes, R Jeffrey AU - Karnes RJ AD - Mayo Clinic, Rochester, MN, USA. FAU - Kurz, Andrea AU - Kurz A AD - Cleveland Clinic Foundation, Cleveland, OH, USA. FAU - Menon, Venu AU - Menon V AD - Cleveland Clinic Foundation, Cleveland, OH, USA. FAU - Sexton, Wade J AU - Sexton WJ AD - H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA. FAU - Slaton, Joel W AU - Slaton JW AD - The University of Oklahoma College of Medicine, Oklahoma City, OK, USA. FAU - Svatek, Robert S AU - Svatek RS AD - The University of Texas Health Science Center San Antonio, San Antonio, TX, USA. FAU - Wilson, Shandra S AU - Wilson SS AD - University of Colorado Health Science Center, Aurora, CO, USA. FAU - Techner, Lee AU - Techner L AD - Cubist Pharmaceuticals, Inc., Lexington, MA, USA. FAU - Bihrle, Richard AU - Bihrle R AD - Indiana University Medical Center, Indianapolis, IN, USA. FAU - Steinberg, Gary D AU - Steinberg GD AD - University of Chicago Medical Center, Chicago, IL, USA. FAU - Koch, Michael AU - Koch M AD - Indiana University Medical Center, Indianapolis, IN, USA. LA - eng SI - ClinicalTrials.gov/NCT00708201 PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20140226 PL - Switzerland TA - Eur Urol JT - European urology JID - 7512719 RN - 0 (Analgesics, Opioid) RN - 0 (Gastrointestinal Agents) RN - 0 (Piperidines) RN - 677C126AET (alvimopan) SB - IM CIN - Nat Rev Urol. 2014 Apr;11(4):186. PMID: 24637421 CIN - Eur Urol. 2014 Aug;66(2):273-4. PMID: 24746972 CIN - Eur Urol. 2015 Feb;67(2):e29. PMID: 25288191 CIN - Eur Urol. 2015 Feb;67(2):e30-1. PMID: 25304758 MH - Aged MH - Analgesics, Opioid/therapeutic use MH - Cardiovascular Diseases/etiology MH - Cystectomy/*adverse effects MH - Defecation MH - Double-Blind Method MH - Eating MH - Female MH - Gastrointestinal Agents/adverse effects/*therapeutic use MH - Gastrointestinal Tract/*physiopathology MH - Humans MH - Ileus/etiology/*prevention & control MH - Length of Stay MH - Male MH - Middle Aged MH - Piperidines/adverse effects/*therapeutic use MH - Postoperative Care MH - Prospective Studies MH - Recovery of Function/*drug effects MH - Time Factors OTO - NOTNLM OT - Alvimopan OT - Enhanced recovery pathway OT - Gastrointestinal recovery OT - Postoperative ileus OT - Radical cystectomy EDAT- 2014/03/19 06:00 MHDA- 2015/07/08 06:00 CRDT- 2014/03/18 06:00 PHST- 2013/10/25 00:00 [received] PHST- 2014/02/13 00:00 [accepted] PHST- 2014/03/18 06:00 [entrez] PHST- 2014/03/19 06:00 [pubmed] PHST- 2015/07/08 06:00 [medline] AID - S0302-2838(14)00165-1 [pii] AID - 10.1016/j.eururo.2014.02.036 [doi] PST - ppublish SO - Eur Urol. 2014 Aug;66(2):265-72. doi: 10.1016/j.eururo.2014.02.036. Epub 2014 Feb 26.