title: Alvimopan accelerates gastrointestinal recovery after radical cystectomy: a multicenter randomized placebo-controlled trial.
abstract: 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.
  
  
  METHODS
  We conducted a randomized double-blind placebo-controlled trial in patients undergoing RC and receiving postoperative intravenous patient-controlled opioid analgesics.
  
  
  METHODS
  Oral alvimopan 12 mg (maximum: 15 inpatient doses) versus placebo.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  RESULTS
  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.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier NCT00708201.
authors.affiliation: University of Michigan, Ann Arbor, MI, USA. Electronic address: ctlee@med.umich.edu.
authors.forename: Cheryl T
authors.initials: CT
authors.lastname: Lee
authors.affiliation: Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Sam S
authors.initials: SS
authors.lastname: Chang
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Ashish M
authors.initials: AM
authors.lastname: Kamat
authors.affiliation: Baylor University, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Gilad
authors.initials: G
authors.lastname: Amiel
authors.affiliation: Bend Memorial Clinic, Bend, OR, USA.
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Beard
authors.affiliation: Cleveland Clinic Foundation, Cleveland, OH, USA.
authors.forename: Amr
authors.initials: A
authors.lastname: Fergany
authors.affiliation: Mayo Clinic, Rochester, MN, USA.
authors.forename: R Jeffrey
authors.initials: RJ
authors.lastname: Karnes
authors.affiliation: Cleveland Clinic Foundation, Cleveland, OH, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Kurz
authors.affiliation: Cleveland Clinic Foundation, Cleveland, OH, USA.
authors.forename: Venu
authors.initials: V
authors.lastname: Menon
authors.affiliation: H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.
authors.forename: Wade J
authors.initials: WJ
authors.lastname: Sexton
authors.affiliation: The University of Oklahoma College of Medicine, Oklahoma City, OK, USA.
authors.forename: Joel W
authors.initials: JW
authors.lastname: Slaton
authors.affiliation: The University of Texas Health Science Center San Antonio, San Antonio, TX, USA.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Svatek
authors.affiliation: University of Colorado Health Science Center, Aurora, CO, USA.
authors.forename: Shandra S
authors.initials: SS
authors.lastname: Wilson
authors.affiliation: Cubist Pharmaceuticals, Inc., Lexington, MA, USA.
authors.forename: Lee
authors.initials: L
authors.lastname: Techner
authors.affiliation: Indiana University Medical Center, Indianapolis, IN, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Bihrle
authors.affiliation: University of Chicago Medical Center, Chicago, IL, USA.
authors.forename: Gary D
authors.initials: GD
authors.lastname: Steinberg
authors.affiliation: Indiana University Medical Center, Indianapolis, IN, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Koch
mesh_terms: D000368:Aged; D000701:Analgesics, Opioid / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000209:etiology; D015653:Cystectomy / Q000009:adverse effects*; D003672:Defecation; D004311:Double-Blind Method; D004435:Eating; D005260:Female; D005765:Gastrointestinal Agents / Q000009:adverse effects / Q000627:therapeutic use*; D041981:Gastrointestinal Tract / Q000503:physiopathology*; D006801:Humans; D045823:Ileus / Q000209:etiology / Q000517:prevention & control*; D007902:Length of Stay; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*; D011182:Postoperative Care; D011446:Prospective Studies; D020127:Recovery of Function / Q000187:drug effects*; D013997:Time Factors
chemical_list: D000701:Analgesics, Opioid; D005765:Gastrointestinal Agents; D010880:Piperidines; C419502:alvimopan
keywords: Alvimopan; Enhanced recovery pathway; Gastrointestinal recovery; Postoperative ileus; Radical cystectomy