ASP (PPI_H2RA) Study-H2RA Versus PPI for the Prevention of Recurrent UGIB in High-risk Users of Low-dose ASA
Condition: Upper Gastrointestinal Bleeding
MeSH terms: Gastrointestinal Hemorrhage; Hemorrhage
Study type: Interventional
Phase: Phase 3

Summary: 
      Peptic ulcer bleeding associated with ASA or NSAIDs is a major cause of hospitalization in
      Hong Kong. The investigators previously showed that ASA or NSAIDs accounted for about half of
      all cases of hospitalizations for peptic ulcer bleeding. Currently, ASA use has contributed
      to about one-third of the bleeding ulcers admitted to the investigators hospital that serves
      a local population of 1.5 million.

      In patients with acute coronary syndrome or acute ischemic stroke who develop ASA-induced
      bleeding peptic ulcers, whether ASA should be discontinued before ulcers have healed is a
      major dilemma. In another double-blind randomized trial, the investigators have shown that
      discontinuation of ASA after endoscopic treatment of bleeding ulcers was associated with a
      significantly increased in mortality within 8 weeks.

      In the absence of safer aspirins, co-therapy with a gastroprotective drug remains the
      dominant preventive strategy. Given the vast number of people taking ASA, however, it is only
      cost-effective to identify and treat those who are at high risk of ulcer bleeding and who
      have a strong indication for ASA use. Data from observational studies and randomized trials
      have consistently shown that PPIs are effective in reducing the risk of ulcer bleeding
      associated with ASA. Other potential preventive strategies include eradication of H. pylori
      infection, substitution of ASA for other non-aspirin anti-platelet drugs, and co-therapy with
      misoprostol or H2RAs.
    

Detailed description: 
      No dose of "low-dose" aspirin (ASA) is safe in terms of the risk if ulcer bleeding. Even at a
      dose as low as 75 mg daily, ASA doubles the risk of ulcer bleeding when compared to the risk
      in non-users. This rise in the incidence was associated with a 44% increase in usage of ASA.
      In Hong Kong, ASA is also a major cause of peptic ulcer complications.

      In the absence of safer aspirins, co-therapy with a gastroprotective drug remains the
      dominant preventive strategy. Given the vast number of people taking ASA, however, it is only
      cost-effective to identify and treat those who are at high risk of ulcer bleeding and who
      have a strong indication for ASA use. Data from observational studies and randomized trials
      have consistently shown that PPIs are effective in reducing the risk of ulcer bleeding
      associated with ASA. Other potential preventive strategies include eradication of H. pylori
      infection, substitution of ASA for other non-aspirin anti-platelet drugs, and co-therapy with
      misoprostol or H2RAs. Among these preventive strategies, co-therapy with a PPI for prevention
      of ulcer bleeding in high-risk ASA users remains the most studied and best proven strategy.

      H2-receptor antagonists (H2RAs) are relatively weak acid suppressing drugs when compared to
      PPIs. Very few studies have evaluated the efficacy of H2RAs in the prevention of peptic ulcer
      bleeding with ASA. Two case-control studies yielded conflicting results with regard to the
      efficacy of H2RAs in reducing the risk of hospitalizations for ulcer bleeding with ASA. There
      is a limited data on the efficacy of H2RAs, however, our local health authority has endorsed
      the use of H2RA as a co-therapy in high-risk ASA users since 2001.

      On the other hand, H2RAs have two potential advantages over PPIs. First, generic H2RAs are
      much cheaper than generic PPIs in Hong Kong. Second, unlike the interaction between PPIs and
      clopidogrel, concomitant use of H2RAs and clopidogrel is not associated with an increased
      risk of recurrent myocardial infarction. Thus, H2RA might be a cheap and safe
      gastroprotective drug in patients requiring dual anti-platelet therapy (i.e., ASA and
      clopidogrel) who require coronary stents.

      In patients with acute coronary syndrome or acute ischemic stroke who develop ASA-induced
      bleeding peptic ulcers, whether ASA should be discontinued before ulcers have healed is a
      major dilemma. In another double-blind randomized trial, we have shown that discontinuation
      of ASA after endoscopic treatment of bleeding ulcers was associated with a significantly
      increased in mortality within 8 weeks.

      The investigators aim to test the hypothesis that PPI is superior to H2RA for the prevention
      of recurrent upper gastrointestinal bleeding in ASA users with a history ulcer bleeding
    

Intervention name(s): Rabeprazole; Famotidine
Intervention type(s): Drug; Drug
Intervention description(s): Rabeprazole 20 mg daily; Famotidine 40mg daily
Other intervention name(s): Pariet; Pepcidine
Intervention MeSH terms: Rabeprazole; Famotidine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: aspirin; PPI; H2RA