title: Double-blind randomized trials of single-tablet ibuprofen/high-dose famotidine vs. ibuprofen alone for reduction of gastric and duodenal ulcers.
abstract: OBJECTIVE
  We performed two 24-week double-blind trials (REDUCE-1 and -2 (Registration Endoscopic Studies to Determine Ulcer Formation of HZT-501 Compared with Ibuprofen: Efficacy and Safety Studies)) to assess whether double-dose famotidine given in a single-tablet combination with ibuprofen (HZT-501) significantly reduces gastric and duodenal ulcers as compared with ibuprofen.
  
  
  METHODS
  Patients (40-80 years) requiring daily non-steroidal anti-inflammatory drugs (NSAIDs) for ≥6 months with no prior ulcer complications, negative H. pylori stool test, and baseline endoscopy showing no ulcers and <5 erosions were randomly assigned in a 2:1 ratio to HZT-501 or identical-appearing ibuprofen 800 mg tablets thrice daily. Study endoscopies were done at 8, 16, and 24 weeks. After unblinding and initial analyses, 12 patients were found to be misclassified as having gastric ulcers based on the adjudication of endoscopy reports, and analyses were re-run.
  
  
  RESULTS
  In REDUCE-1, the primary end point analysis of gastric ulcers at 24 weeks with HZT-501 vs. ibuprofen was 12.7% vs. 22.9% (P=0.0044) in the post-adjudication analysis. In REDUCE-2, the primary end point analysis of upper gastrointestinal (GI) ulcers was 13.0% vs. 20.5% (P=0.0587) in the post-adjudication analysis. Prespecified pooled analyses showed significantly fewer gastric (12.5% vs. 20.7%) and duodenal ulcers (1.1% vs. 5.1%) with HZT-501 vs. ibuprofen. Proportional hazards analysis of multiple potential risk factors showed the risk ratio of upper GI ulcers with HZT-501 vs. ibuprofen was 0.46, 95% confidence interval was 0.34-0.61.
  
  
  CONCLUSIONS
  Combined results of the REDUCE studies indicate that double-dose famotidine plus ibuprofen, given as a combination tablet, decreases endoscopic upper GI ulcers as compared with ibuprofen alone.
authors.affiliation: Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, California, USA. llaine@usc.edu
authors.forename: Loren
authors.initials: L
authors.lastname: Laine
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Kivitz
authors.forename: Alfonso E
authors.initials: AE
authors.lastname: Bello
authors.forename: Amy Y
authors.initials: AY
authors.lastname: Grahn
authors.forename: Michael H
authors.initials: MH
authors.lastname: Schiff
authors.forename: Ali S
authors.initials: AS
authors.lastname: Taha
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use*; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D004311:Double-Blind Method; D004338:Drug Combinations; D004381:Duodenal Ulcer / Q000188:drug therapy*; D016099:Endoscopy, Gastrointestinal; D015738:Famotidine / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012307:Risk Factors; D013276:Stomach Ulcer / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D004338:Drug Combinations; D015738:Famotidine; D007052:Ibuprofen