Gastric Ulcer Induced by Antiplatelet Agent, Proton Pump Inhibitor, Ulcer of the Gastrointestinal Tract
Conditions
Keywords
Coronary Artery Bypass Graft, Dual Antiplatelet Therapy, Gastrointestinal, Mucosal Injury, Proton Pump Inhibitor
Brief 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 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.
Interventions
DRUGPantoprazole
Pantoprazole (40mg qd) will be concomitant used with DAPT
Sponsors
Ruijin Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Each patient should meet all of the inclusion criteria and none of the
Exclusion criteria
for this study: 1. Provision of informed consent prior to any study specific procedures. 2. CABG surgery is performed for the first time. 3. 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. 4. Concomitant use of pantoprazole (40mg qd) for at least 1 moth following CABG surgery. 5. Willing to undergo EGD twice a year (at 6th and 12th month following CABG surgery, respectively). 6. Willing to undergo 13C-UBT prior to CABG surgery.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Cumulative incidence of gastroduodenal erosions and ulcers. | up to 12 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of gastroduodenal erosions and ulcers. | up to 6 months | — |
| Incidence of upper GI major bleeding according to TIMI criteria. | up to 12 months | — |
| Incidence of upper GI minor bleeding according to TIMI criteria | up to 12 months | — |
| Incidence of major cardiovascular events (MACE, composite of cardiovascular death, myocardial infarctions, or stroke). | up to 12 months | Safety Issue: Yes |
| Incidence of grafts failure. | up to 12 months | Safety Issue: Yes |
Countries
China
Outcome results
None listed