ASP (PPI_H2RA) Study-H2RA Versus PPI for the Prevention of Recurrent UGIB in High-risk Users of Low-dose ASA

NCT ID: NCT01408186

Last Updated: 2017-04-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 264 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-01-31
• Study Completion Date: 2016-11-30

Brief 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

Conditions

Upper Gastrointestinal Bleeding

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Rabeprazole

Tablet 20mg daily for 12 months

Group Type: ACTIVE_COMPARATOR

Rabeprazole

Intervention Type: DRUG

Rabeprazole 20 mg daily

Famotidine

Tablet 40mg daily for 12 months

Group Type: ACTIVE_COMPARATOR

Famotidine

Intervention Type: DRUG

Famotidine 40mg daily

Interventions

Rabeprazole

Rabeprazole 20 mg daily

Intervention Type: DRUG

Famotidine

Famotidine 40mg daily

Intervention Type: DRUG

Other Intervention Names

Pariet; Pepcidine

Eligibility Criteria

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 or 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chinese University of Hong Kong

OTHER

Sponsor Role: lead

Responsible Party

Francis KL Chan

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Francis KL Chan, MD

Role: PRINCIPAL_INVESTIGATOR

Chinese University of Hong Kong

Locations

Prince of Wales Hospital

Hong Kong, , Hong Kong

Second Department of Internal Medicine, Shimane University Faculty of Medicine, Izumo, Japan

Izumo, , Japan

Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan

Kyoto, , Japan

Department of Gastroenterology, Osaka City General Hospital, Osaka, Japan (Satellite hospital of Osaka City University)

Osaka, , Japan

Department of Gastroenterology, Osaka City University Graduate School of Medicine

Osaka, , Japan

Department of Gastroenterology, Takarazuka Municipal Hospital, Hyogo, Japan (Satellite hospital of Osaka City University)

Osaka, , Japan

Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka, Japan

Osaka, , Japan

Department of Internal Medicine and Gastroenterology, Saga Medical School, Saga, Japan

Saga, , Japan

Countries

Hong Kong; Japan

References

Chan FK, Kyaw M, Tanigawa T, Higuchi K, Fujimoto K, Cheong PK, Lee V, Kinoshita Y, Naito Y, Watanabe T, Ching JY, Lam K, Lo A, Chan H, Lui R, Tang RS, Sakata Y, Tse YK, Takeuchi T, Handa O, Nebiki H, Wu JC, Abe T, Mishiro T, Ng SC, Arakawa T. Similar Efficacy of Proton-Pump Inhibitors vs H2-Receptor Antagonists in Reducing Risk of Upper Gastrointestinal Bleeding or Ulcers in High-Risk Users of Low-Dose Aspirin. Gastroenterology. 2017 Jan;152(1):105-110.e1. doi: 10.1053/j.gastro.2016.09.006. Epub 2016 Sep 15.

Reference Type: DERIVED

PMID: 27641510 (View on PubMed)

Other Identifiers

APH Study

Identifier Type: -

Identifier Source: org_study_id