Gastric Ulcer Induced by Antiplatelet AgentPhase 4DACAB-GI-2NCT03038009
Proton Pump Inhibitor Prevent Dual Antiplatelet Agents Induced Gastrointestinal Ulcer After Coronary Artery Bypass Graft
A Phase 4 study testing Pantoprazole in people with Gastric Ulcer Induced by Antiplatelet Agent and Ulcer of the Gastrointestinal Tract, run by Ruijin Hospital at 1 site in China.
Trial summary
The purpose of this study is to determine whether 12-month prophylactic treatment with pantoprazole is superior to 1-month therapy without major cardiovascular events (MACE) increased significantly, in prevention of dual antiplatelet therapy (DAPT)-induced upper gastrointestinal (GI) mucosal injury after coronary… Read more about this study
- Who is it for?
- Ages 30 to 80 years
- Conditions the study is for
- Gastric Ulcer Induced by Antiplatelet Agent, Ulcer of the Gastrointestinal Tract, Proton Pump Inhibitor
- What is being tested?
- Pantoprazole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteChina
- Study dates
- Oct 2018to Dec 2020
- Phase
- Phase 4
- 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 30 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Each patient should meet all of the inclusion criteria and none of the exclusion criteria for this study:
- Provision of informed consent prior to any study specific procedures.
- CABG surgery is performed for the first time.
- Need 12-month DAPT (aspirin 100mg qd plus clopidogrel 75mg qd or aspirin 100mg qd plus ticagrelor 90mg bid depending on randomisation) immediately following CABG surgery according to the guideline.
- Concomitant use of pantoprazole (40mg qd) for at least 1 moth following CABG surgery.
- Willing to undergo EGD twice a year (at 6th and 12th month following CABG surgery, respectively).
- Willing to undergo 13C-UBT prior to CABG surgery.
Who cannot join
- Patients should not enter the study if any of the following exclusion criteria are fulfilled.
- History of previous active peptic ulcer within 3 months prior to enrollment.
- Planned use of PPI to treat gastric-acid associated diseases (e.g. gastroesophageal reflux disease, GERD)
- Contraindications for aspirin, clopidogrel, ticagrelor and pantoprazole use (e.g. known allergy)
- Anticipated concomitant oral or intravenous therapy with strong cytochrome P450 3A4 (CYP3A4) inhibitors or CYP3A4 substrates with narrow therapeutic indices, that cannot be stopped for the course of the study.
- Strong inhibitors: ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin, nefazadone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir
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- CYP3A4 substrates with narrow therapeutic index: quinidine, simvastatin at doses > 40mg daily or lovastatin at doses > 40mg daily.
- Need for chronic oral anticoagulant therapy or chronic low-molecular-weight heparin.
- History of previous intracerebral bleeding at any time, GI bleeding within the past 3 months prior to enrollment, or major surgery within 30 days prior to enrollment.
- Known moderate to severe liver disease (e.g. gastroesophageal varices, ascites and/ or clinical signs of coagulopathy)
- Renal failure requiring dialysis.
- Women of child-bearing potential who are not willing to use a medically accepted method of contraception that is considered reliable in the judgement of investigator OR women who have a positive pregnancy test at enrolment or randomisation OR women who are breasting-feeding.
- Inability of patient to understand and/or comply with study procedures and/or follow up, in the opinion of the investigator, OR any conditions that, in the opinion of the investigator, many render the patient unable to complete the study.
- Any condition which in the opinion of the investigator would make it unsafe or unsuitable for the patient to participate in this study (eg, long-term concomitant treatment with non-steroidal anti-inflammatory drugs [NSAIDs]), or any condition outside the atherothrombotic study area with a life expectancy of less than 2 years based on investigator's judgement.
- Paticipation in another clinical study with an investigational product within 28 days prior to enrolment or previous randomization to an investigational product in another ongoing clinical study. Participation in any previous study with clopidogrel or tigagrelor.
Trial locations and contacts
1 site in 1 country.
China1 site
Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
Shanghai, 200025
About this study
Official title: Evaluation of the Efficacy and Safety of Different Duration of Proton Pump Inhibitor for Prevention of Upper Gastrointestinal Mucosal Injury in Patients Taking 12-month Dual Antiplatelet Therapy After Coronary Artery Bypass Graft Surgery
The purpose of this study is to determine whether 12-month prophylactic treatment with pantoprazole is superior to 1-month therapy without major cardiovascular events (MACE) increased significantly, in prevention of dual antiplatelet therapy (DAPT)-induced upper gastrointestinal (GI) mucosal injury after coronary artery bypass graft (CABG) surgery. The potentially serious harm of DAPT on gastroduodenal mucosa will be assessed by esophagogastroduodenoscopy (EGD).
Read the detailed description
Endoscopic evaluation of gastroduodenal mucosal injury:
Based on the modified Lanza score, the new endoscopic evaluation system established in the DACAB-GI-1 study includes 6 grades of mucosal injuries. Grade 0: normal mucosa; Grade 1: erythema or petechiae only; Grade 2: 1 to 2 erosive lesions; Grade 3: 3 to 10 erosive lesions; Grade 4: more than 10 erosive lesions or small ulcers (diameter: 3-5mm); Grade 5: an ulcer is greater than 5 mm in diameter. Comprehensive results of gastroduodenal mucosal injury will be marked as G0-5 (G: gastro) and D0-5 (D: duodeno) together. Mild injury was defined as level II or less. Severe injury was defined from level III to V, which should be treated with proton pump inhibitor (PPI) to decrease the risk of upper GI bleeding. The new level system is as following: Level 0: G0D0; Level I: G1D0-1/G0D1; Level II: G2D0-2/G0-1D2; Level III: G3D0-3/G0-2D3; Level IV: G4D0-4/G0-3D4; Level V: G5D0-5/G0-4D5.
Sample size justification:
Until now, no published data or reference is available for the efficacy of pantoprazole when concomitant use with DAPT. The results from the preliminary study (DACAB-GI-1) showed that the percentage of serious gastroduodenal mucosal lesions (Level III-V) in patients treated with PPIs for 1, 3 and more than 6 months were 36.76%, 28.45% and 17.65%, respectively. Therefore, the efficacy difference of pantoprazole is estimated to be 18% between 2 groups. The average incidence of gastroduodenal mucosal injury is estimated to be 36% in the control group (1-month therapy of pantoprazole), and the corresponding incidence in the experimental group (12-month therapy of pantoprazole) is estimated to be 18%.
The determination of minimal sample size is as following: Group sample sizes of 93 in the experimental group and 93 in the control group achieve 80% power to detect a difference between the group proportions of -18%. The proportion in the experimental group is assumed to be 36% under the null hypothesis and 18% under the alternative hypothesis. The proportion in the control group is 36%. The test statistic used is Pearson Chi-Squared test. The significance level of the test was targeted at 0.05. The significance level actually achieved by this design is 0.0522. Considering 10% of the lost and/or drop-out rate, the final sample size estimated will be 104 in the experimental group and control group, respectively. The total sample size is no less than 208.
- Conditions
- Gastric Ulcer Induced by Antiplatelet Agent, Ulcer of the Gastrointestinal Tract, Proton Pump Inhibitor
- Being tested
- Pantoprazole
- Keywords
- Coronary Artery Bypass Graft, Dual Antiplatelet Therapy, Gastrointestinal, Mucosal Injury, Proton Pump Inhibitor
- Medical subject headings
- Peptic Ulcer
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PantoprazoleDrug
Also called PANTOLOC, Tablet from Takeda Pharmaceutical Company Limited
Pantoprazole (40mg qd) will be concomitant used with DAPT
| Study group | Role | What they receive |
|---|---|---|
| One-month therapy | Active comparator | Pantoprazole, 40mg, tablet, oral, once daily for 1 month. Receives: Drug: Pantoprazole |
| Twelve-month therapy | Experimental | Pantoprazole, 40mg, tablet, oral, once daily for 12 months. Receives: Drug: Pantoprazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cumulative incidence of gastroduodenal erosions and ulcers.
Measured: up to 12 months
Secondary outcomes (5)
Incidence of gastroduodenal erosions and ulcers.
Measured: up to 6 months
Incidence of upper GI major bleeding according to TIMI criteria.
Measured: up to 12 months
Incidence of upper GI minor bleeding according to TIMI criteria
Measured: up to 12 months
Incidence of major cardiovascular events (MACE, composite of cardiovascular death, myocardial infarctions, or stroke).
Safety Issue: Yes
Measured: up to 12 months
Incidence of grafts failure.
Safety Issue: Yes
Measured: up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2017 (estimated)
- Study startOct 2018 (estimated)
- Primary completionSep 2020 (estimated)
- Study completionDec 2020 (estimated)
Why it stopped: A new registration has been submitted due to a redesign of the study protocol.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Gastric Ulcer Induced by Antiplatelet AgentStudies of the same condition, open and under way.
- More trials run by Ruijin HospitalThe 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 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ruijin Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Lifen YU, Ruijin Hospital
- Investigators
- Lifen Yu, MD, Ph.D, Principal investigator, Ruijin Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03038009
- Sponsor's protocol ID
- IISR-2016-101603
- Acronym
- DACAB-GI-2
- Status last verified
- Apr 2019
- First submitted
- 29 Jan 2017
- Last updated
- 9 Apr 2019
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Efficacy and Safety of Different Duration of Proton Pump Inhibitor for Prevention of Upper Gastrointestinal Mucosal Injury in Patients Taking 12-month Dual Antiplatelet Therapy After Coronary Artery Bypass Graft Surgery
- ClinicalTrials.gov ID
- NCT03038009
- Acronym / sponsor ID
- DACAB-GI-2 / IISR-2016-101603
- Conditions
- Gastric Ulcer Induced by Antiplatelet Agent, Ulcer of the Gastrointestinal Tract, Proton Pump Inhibitor
- Keywords
- Coronary Artery Bypass Graft, Dual Antiplatelet Therapy, Gastrointestinal, Mucosal Injury, Proton Pump Inhibitor
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: A new registration has been submitted due to a redesign of the study protocol.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Ruijin HospitalUniversity, hospital or other
- Study start
- Oct 2018 (estimated)
- Primary completion
- Sep 2020 (estimated)
- Study completion
- Dec 2020 (estimated)
- First posted
- 31 Jan 2017 (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.
The purpose of this study is to determine whether 12-month prophylactic treatment with pantoprazole is superior to 1-month therapy without major cardiovascular events (MACE) increased significantly, in prevention of dual antiplatelet therapy (DAPT)-induced upper gastrointestinal (GI) mucosal injury after coronary artery bypass graft (CABG) surgery. The potentially serious harm of DAPT on gastroduodenal mucosa will be assessed by esophagogastroduodenoscopy (EGD).
Detailed description
Endoscopic evaluation of gastroduodenal mucosal injury:
Based on the modified Lanza score, the new endoscopic evaluation system established in the DACAB-GI-1 study includes 6 grades of mucosal injuries. Grade 0: normal mucosa; Grade 1: erythema or petechiae only; Grade 2: 1 to 2 erosive lesions; Grade 3: 3 to 10 erosive lesions; Grade 4: more than 10 erosive lesions or small ulcers (diameter: 3-5mm); Grade 5: an ulcer is greater than 5 mm in diameter. Comprehensive results of gastroduodenal mucosal injury will be marked as G0-5 (G: gastro) and D0-5 (D: duodeno) together. Mild injury was defined as level II or less. Severe injury was defined from level III to V, which should be treated with proton pump inhibitor (PPI) to decrease the risk of upper GI bleeding. The new level system is as following: Level 0: G0D0; Level I: G1D0-1/G0D1; Level II: G2D0-2/G0-1D2; Level III: G3D0-3/G0-2D3; Level IV: G4D0-4/G0-3D4; Level V: G5D0-5/G0-4D5.
Sample size justification:
Until now, no published data or reference is available for the efficacy of pantoprazole when concomitant use with DAPT. The results from the preliminary study (DACAB-GI-1) showed that the percentage of serious gastroduodenal mucosal lesions (Level III-V) in patients treated with PPIs for 1, 3 and more than 6 months were 36.76%, 28.45% and 17.65%, respectively. Therefore, the efficacy difference of pantoprazole is estimated to be 18% between 2 groups. The average incidence of gastroduodenal mucosal injury is estimated to be 36% in the control group (1-month therapy of pantoprazole), and the corresponding incidence in the experimental group (12-month therapy of pantoprazole) is estimated to be 18%.
The determination of minimal sample size is as following: Group sample sizes of 93 in the experimental group and 93 in the control group achieve 80% power to detect a difference between the group proportions of -18%. The proportion in the experimental group is assumed to be 36% under the null hypothesis and 18% under the alternative hypothesis. The proportion in the control group is 36%. The test statistic used is Pearson Chi-Squared test. The significance level of the test was targeted at 0.05. The significance level actually achieved by this design is 0.0522. Considering 10% of the lost and/or drop-out rate, the final sample size estimated will be 104 in the experimental group and control group, respectively. The total sample size is no less than 208.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| One-month therapy | Active comparator | Drug: PantoprazolePantoprazole, 40mg, tablet, oral, once daily for 1 month. |
| Twelve-month therapy | Experimental | Drug: PantoprazolePantoprazole, 40mg, tablet, oral, once daily for 12 months. |
Who may qualify
- Ages
- 30 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Each patient should meet all of the inclusion criteria and none of the exclusion criteria for this study:
- Provision of informed consent prior to any study specific procedures.
- CABG surgery is performed for the first time.
- Need 12-month DAPT (aspirin 100mg qd plus clopidogrel 75mg qd or aspirin 100mg qd plus ticagrelor 90mg bid depending on randomisation) immediately following CABG surgery according to the guideline.
- Concomitant use of pantoprazole (40mg qd) for at least 1 moth following CABG surgery.
Key exclusion criteria (15 listed)
- Patients should not enter the study if any of the following exclusion criteria are fulfilled.
- History of previous active peptic ulcer within 3 months prior to enrollment.
- Planned use of PPI to treat gastric-acid associated diseases (e.g. gastroesophageal reflux disease, GERD)
- Contraindications for aspirin, clopidogrel, ticagrelor and pantoprazole use (e.g. known allergy)
- Anticipated concomitant oral or intravenous therapy with strong cytochrome P450 3A4 (CYP3A4) inhibitors or CYP3A4 substrates with narrow therapeutic indices, that cannot be stopped for the course of the study.
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 |
|---|---|---|
| PantoprazoleAlso: PANTOLOC, Tablet from Takeda Pharmaceutical Company LimitedPantoprazole (40mg qd) will be concomitant used with DAPT | Drug | One-month therapy, Twelve-month therapy |
Primary outcome
Cumulative incidence of gastroduodenal erosions and ulcers.
Time frame: up to 12 months
5 secondary outcomes
Incidence of gastroduodenal erosions and ulcers.
Time frame: up to 6 months
Incidence of upper GI major bleeding according to TIMI criteria.
Time frame: up to 12 months
Incidence of upper GI minor bleeding according to TIMI criteria
Time frame: up to 12 months
Incidence of major cardiovascular events (MACE, composite of cardiovascular death, myocardial infarctions, or stroke).
Time frame: up to 12 months
Incidence of grafts failure.
Time frame: up to 12 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Apr 2019.
- Individual participant dataSharing planned: No
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.
Lifen Yu, MD, Ph.D principal investigator
Ruijin Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Pantoprazole in people with Gastric Ulcer Induced by Antiplatelet Agent and Ulcer of the Gastrointestinal Tract, run by Ruijin Hospital at 1 site in China.
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 7 inclusion and 15 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: withdrawn, as of the sponsor's last update on 9 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 was withdrawn before enrolling participants, so there are no results.
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?
Cumulative incidence of gastroduodenal erosions and ulcers. (time frame: up to 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Apr 2019.