Upper Gastrointestinal BleedingPhase 3NCT01408186
ASP (PPI_H2RA) Study-H2RA Versus PPI for the Prevention of Recurrent UGIB in High-risk Users of Low-dose ASA
A Phase 3 study testing Rabeprazole and Famotidine in people with Upper Gastrointestinal Bleeding, run by Chinese University of Hong Kong at 8 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Upper Gastrointestinal Bleeding
- What is being tested?
- Rabeprazole and Famotidine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 264 participants
- Where
- 8 sitesin 2 countries
- Study dates
- Jan 2011to Nov 2016
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- A history of documented peptic ulcer bleeding (self-reported history without confirmation by the clinician is not acceptable)
- Negative tests for H. pylori or successful eradication of H. pylori based on urease test or histology
- Expected regular use of ASA for the duration of the trial
- Age ≥ 18
- Written informed consent obtained
Who cannot join
- A history of gastric or duodenal surgery other than patch repair
- Severe erosive esophagitis (LA grade C or D)
- Gastric outlet obstruction
- Terminal illness
- Active malignancies
Trial locations and contacts
8 sites in 2 countries.
8 sites in 2 countries
Japan7 sites
Second Department of Internal Medicine, Shimane University Faculty of Medicine, Izumo, Japan
Izumo
Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
Kyoto
Department of Gastroenterology, Osaka City General Hospital, Osaka, Japan (Satellite hospital of Osaka City University)
Osaka
Department of Gastroenterology, Osaka City University Graduate School of Medicine
Osaka
Department of Gastroenterology, Takarazuka Municipal Hospital, Hyogo, Japan (Satellite hospital of Osaka City University)
Osaka
Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka, Japan
Osaka
Department of Internal Medicine and Gastroenterology, Saga Medical School, Saga, Japan
Saga
About this study
Official title: Histamine-2 Receptor Antagonist Versus Proton-Pump Inhibitor for the Prevention of Recurrent Upper Gastrointestinal Bleeding (UGI) in High-risk Users of Low-dose Aspirin (ASA)
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.
Read the 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
- Being tested
- Rabeprazole, Famotidine
- Keywords
- aspirin, PPI, H2RA
- Medical subject headings
- Gastrointestinal Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RabeprazoleDrug
Also called Pariet
Rabeprazole 20 mg daily
FamotidineDrug
Also called Pepcidine
Famotidine 40mg daily
| Study group | Role | What they receive |
|---|---|---|
| Rabeprazole | Active comparator | Tablet 20mg daily for 12 months Receives: Drug: Rabeprazole |
| Famotidine | Active comparator | Tablet 40mg daily for 12 months Receives: Drug: Famotidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
recurrent non-variceal upper GI bleeding
defined as hematemesis, melena or a decrease in hemoglobin of at least 2 g/dL with ulcers or bleeding erosions confirmed by endoscopy, and adjudicated by an independent committee
Measured: 12 months
Secondary outcomes (3)
lower GI bleeding
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.
Measured: 12 Months
atherothrombotic events
atherothrombotic events
Measured: 12 months
A composite of recurrent upper GI bleeding or recurrent endoscopic ulcers
defined as hematemesis, melena or a decrease in hemoglobin of at least 2 g/dL with ulcers or bleeding erosions confirmed by endoscopy, and adjudicated by an independent committee
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2011 (estimated)
- Study startJan 2011
- Primary completionNov 2015
- Study completionNov 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Upper Gastrointestinal BleedingStudies of the same condition, open and under way.
- More trials run by Chinese University of Hong KongThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 264 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chinese University of Hong Kong
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Francis KL Chan, Chinese University of Hong Kong
- Investigators
- Francis KL Chan, MD, Principal investigator, Chinese University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01408186
- Sponsor's protocol ID
- APH Study
- Status last verified
- Apr 2017
- First submitted
- 2 Aug 2011
- Last updated
- 21 Apr 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 27641510
Study at a glance
From the registry record, last updated by the sponsor on 21 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Histamine-2 Receptor Antagonist Versus Proton-Pump Inhibitor for the Prevention of Recurrent Upper Gastrointestinal Bleeding (UGI) in High-risk Users of Low-dose Aspirin (ASA)
- ClinicalTrials.gov ID
- NCT01408186
- Acronym / sponsor ID
- APH Study
- Conditions
- Upper Gastrointestinal Bleeding
- Keywords
- aspirin, PPI, H2RA
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 264 participants (actual)
- Lead sponsor
- Chinese University of Hong KongUniversity, hospital or other
- Study start
- Jan 2011
- Primary completion
- Nov 2015 (actual)
- Study completion
- Nov 2016 (actual)
- First posted
- 3 Aug 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Rabeprazole | Active comparator | Drug: RabeprazoleTablet 20mg daily for 12 months |
| Famotidine | Active comparator | Drug: FamotidineTablet 40mg daily for 12 months |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- A history of documented peptic ulcer bleeding (self-reported history without confirmation by the clinician is not acceptable)
- Negative tests for H. pylori or successful eradication of H. pylori based on urease test or histology
- Expected regular use of ASA for the duration of the trial
- Age ≥ 18
- Written informed consent obtained
Key exclusion criteria (5 listed)
- A history of gastric or duodenal surgery other than patch repair
- Severe erosive esophagitis (LA grade C or D)
- Gastric outlet obstruction
- Terminal illness
- Active malignancies
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RabeprazoleAlso: ParietRabeprazole 20 mg daily | Drug | Rabeprazole |
| FamotidineAlso: PepcidineFamotidine 40mg daily | Drug | Famotidine |
Primary outcome
recurrent non-variceal upper GI bleeding
Time frame: 12 months
defined as hematemesis, melena or a decrease in hemoglobin of at least 2 g/dL with ulcers or bleeding erosions confirmed by endoscopy, and adjudicated by an independent committee
3 secondary outcomes
lower GI bleeding
Time frame: 12 Months
atherothrombotic events
Time frame: 12 months
A composite of recurrent upper GI bleeding or recurrent endoscopic ulcers
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Apr 2017.
- Derived from this study: PubMed 27641510Chan 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Francis KL Chan, MD principal investigator
Chinese University of Hong Kong
8 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Rabeprazole and Famotidine in people with Upper Gastrointestinal Bleeding, run by Chinese University of Hong Kong at 8 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Japan, Hong Kong. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
recurrent non-variceal upper GI bleeding (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01408186, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Apr 2017.