H2RA VS PPI for the Prevention of Ulcer Bleeding Associated With Low-dose Aspirin in Patients With Very High Ulcer Risk

This study is currently recruiting participants.
Verified February 2014 by Chinese University of Hong Kong
Sponsor:
Information provided by (Responsible Party):
Francis KL Chan, Chinese University of Hong Kong
ClinicalTrials.gov Identifier:
NCT01408186
First received: August 2, 2011
Last updated: February 19, 2014
Last verified: February 2014

August 2, 2011
February 19, 2014
January 2011
April 2015   (final data collection date for primary outcome measure)
Recurrent ulcer bleeding [ Time Frame: 12 months ] [ Designated as safety issue: No ]
Hematemesis or melena with ulcers or bleeding erosions confirmed by endoscopy, or a decrease in hemoglobin of at least 2 g/dL in the presence of endoscopically proven ulcers or multiple erosions. Bleeding erosions are defined as flat mucosal breaks of any size in the presence of blood/coffee ground in patients with hematemesis or melena, or >=10 erosions in patients with >=2 g/dL decrease in hemoglobin.
Recurrent ulcer bleeding [ Time Frame: 12 months ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01408186 on ClinicalTrials.gov Archive Site
  • Lower GI bleeding [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Lower gastrointestinal bleeding is defined by either melena or rectal bleeding causing hospital admission or transfusion, with negative results on upper endoscopy, or by a decrease in hemoglobin of at least 2 g/dL in association with negative results on upper endoscopy and no other explanations for the anemia.
  • serious cardiothrombotic events [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
    Serious cardiothrombotic events
Lower GI bleeding, serious cardiothrombotic events, and endoscopic ulcers/multiple erosions [ Time Frame: 12 months ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
H2RA VS PPI for the Prevention of Ulcer Bleeding Associated With Low-dose Aspirin in Patients With Very High Ulcer Risk
Histamine-2 Receptor Antagonist Versus Proton-Pump Inhibitor for the Prevention of Ulcer Bleeding Associated With Low-dose Aspirin in Patients With Very High Ulcer Risk (ASP (PPI_H2RA) Study)

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.

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 ulcer bleeding in ASA users with a history ulcer bleeding.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Peptic Ulcer Bleeding
  • Drug: Rabeprazole
    Rabeprazole 20 mg daily
    Other Name: Pariet
  • Drug: Famotidine
    Famotidine 40mg daily
    Other Name: Pepcidine
  • Active Comparator: Rabeprazole
    Tablet 20mg daily for 12 months
    Intervention: Drug: Rabeprazole
  • Active Comparator: Famotidine
    Tablet 40mg daily for 12 months
    Intervention: Drug: Famotidine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
332
Not Provided
April 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. A history of documented peptic ulcer bleeding (self-reported history without confirmation by the clinician is not acceptable)
  2. Negative tests for H. pylori or successful eradication of H. pylori based on urease test and histology
  3. Expected regular use of ASA for the duration of the trial
  4. Age ≥ 18
  5. Written informed consent obtained

Exclusion Criteria:

  1. A history of gastric or duodenal surgery other than patch repair
  2. Severe erosive esophagitis (LA grade C or D)
  3. Gastric outlet obstruction
  4. Terminal illness
  5. Active malignancies
Both
18 Years and older
No
Contact: Jessica YL Ching, MPH +852 2632 3524 jessicaching@cuhk.edu.hk
China
 
NCT01408186
APH Study
No
Francis KL Chan, Chinese University of Hong Kong
Chinese University of Hong Kong
Not Provided
Principal Investigator: Francis KL Chan, MD Chinese University of Hong Kong
Chinese University of Hong Kong
February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP