Clinical trial NCT04728516: The Effect of Dual Eradication Therapy vs PPI on Gastrointestinal Bleeding in ACS Patients
Official title: The Effect of Vonoprazan-based Dual Eradication Therapy vs PPI Treatment on Gastrointestinal Bleeding in ACS Patients With Hp Infection and Coronary Stents: an Open-label, Randomized, Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Acute Coronary Syndrome
Helicobacter Pylori Infection
Lead sponsor: Qilu Hospital of Shandong University
Sponsor class: OTHER
First posted: 2021-01-28
Enrollment: 2600
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Patients with acute coronary syndrome (ACS) after Percutaneous Coronary Intervention (PCI) require routine treatment with dual antiplatelet (DAPT) treatment, but with the high risk of bleeding, gastrointestinal bleeding is the most common type of major bleeding. Helicobacter pylori (Hp) infection is a high-risk factor for gastrointestinal bleeding, with an incidence of about 50%. Foreign authoritative DAPT guidelines do not give individual guidance to Hp-infected patients. It is recommended that those with high bleeding risk should be combined with proton pump inhibitors (PPI), but long-term compliance with PPI is not ideal. Authoritative experts in China have agreed to recommend Hp detection and eradication therapy for DAPT patients, but loss of evidence. Vonoprazan is a novel potassium ion competitive acid blocker, based on Vonoprazan's dual Hp eradication therapy is simple and effective. Our team will conduct a multi-center, open-label, randomized controlled clinical trial using a non-inferior design to compare the combination of Vonoprazan + amoxicillin combined with pantoprazole (PPI) for 6 months after PCI on the bleeding events of the digestive tract.

Detailed description: This study plans to enroll 2600 patients, 1300 patients in each group, in the project participating hospitals who received coronary stenting and are expected to undergo DAPT ≥6 months after operation. Hp13C-urea breath test and serum Hp antibody scores Type detection, patients with positive Hp infection.

Antiplatelet drugs (DAPT) use aspirin 100 mg qd, plus clopidogrel 75 mg qd or aspirin 100mg qd plus ticagrelor 90 mg bid. The specific medication is evaluated and decided by the interventional doctor.

After the subjects in each center signed a written informed consent form, they randomly divided each test case into a test group or a control group at a 1:1 ratio:

1. Test group:

   In the project participating hospitals who received coronary stenting and are expected to undergo DAPT ≥6 months after operation. Hp13C-urea breath test and serum Hp antibody scores Type detection, patients with positive Hp infection. Antiplatelet drugs (DAPT) use aspirin 100 mg qd, plus clopidogrel 75 mg qd or aspirin 100 mg qd, plus ticagrelor 90 mg bid. The specific medication is evaluated and decided by the interventional doctor.

   H. pylori eradication using a dual eradication regimen, a course of 14 days, followed up to 6 months after randomization; the treatment regimen is as follows: routine use of Vonoprazan 20mg bid + amoxicillin 1g tid, a duration of 14 days(Considering the high drug resistance rate of Hp strains in China, we increase the course of eradication treatment to 14 days) .

   i. Introduce the subject to the possible adverse reactions to the dual eradication at the informed stage, and inform the subject that when the adverse reaction occurs, the researcher should be contacted as soon as possible to deal with it as soon as possible to reduce unnecessary shedding. For patients who are unable to tolerate the combination therapy and fall off, record the reason for the incomplete treatment and the corresponding time point, and continue the safety visit.

   ii. More than 1 month after completion of the dual eradication (scheduled at the 12th week of follow-up, visit 3), use the 13C-urea breath test to retest Hp infection. For subjects who failed H. pylori eradication, in the Department of Gastroenterology Remedial treatment under the guidance of a doctor.
2. Control group:

In the project participating hospitals who received coronary stenting and are expected to undergo DAPT ≥ 6 months after operation. Hp13C-urea breath test and serum Hp antibody scores Type detection, patients with positive Hp infection. Antiplatelet drugs (DAPT) use aspirin 100 mg qd, plus clopidogrel 75 mg qd or aspirin 100 mg qd plus ticagrelor 90 mg bid. The specific medication is evaluated and decided by the interventional doctor. Taking pantoprazole 40 mg daily, followed up to 6 months after randomization.

Eligibility criteria: Inclusion Criteria:

1. Patients with ACS and PCI treatment and postoperative DAPT ≥ 6 months;
2. Hp infection is positive;
3. Age ≥18 years old;
4. The patient himself or his authorized client signs the subject's consent.

Exclusion Criteria:

1. Previous history of gastrointestinal ulcer bleeding;
2. Long-term use of PPI and H2 receptor inhibitors in the past;
3. Complicated with gastroesophageal varices, or after gastrectomy;
4. Those who are taking anti-coagulation drugs such as vitamin K antagonists (warfarin) and have bleeding tendency;
5. Recently received fibrinolytic therapy (using fibrin-specific drugs within 24 hours before randomization, or using non-fibrin-specific drugs within 48 hours before randomization);
6. Recently accepted (within 30 days before randomization) or planned to undergo coronary artery bypass grafting (CABG);
7. Combining active bleeding or coagulation dysfunction (indicator);
8. In patients with liver and kidney disease, serum creatinine is greater than 150 μmol/L, alanine aminotransferase and aspartate aminotransferase increase ≥2 times from the normal value;
9. Complicated with hemorrhagic stroke, intracranial tumor, arteriovenous malformation or aneurysm;
10. Anemia (adult male hemoglobin less than 120 g/L or red blood cells less than 4×1012/L, adult female hemoglobin less than 105 g/L or red blood cells less than 3.5×1012/L);
11. Systemic glucocorticoid application;
12. Have taken antibiotics and other drugs that affect the flora in the stomach within the past month;
13. A history of allergy to aspirin, clopidogrel, ticagrelor, pantoprazole, penicillin and other test drugs;
14. Pregnancy or breastfeeding women and subjects of childbearing age who do not want to take contraceptive measures;
15. With malignant tumors and other diseases, the expected survival time is less than 1 year;
16. Patients who participated in clinical trials of other drugs or are participating in clinical studies of other new drugs within 30 days before enrollment;
17. Complicated with mental illness or severe neurosis;
18. Can't express subjective discomfort symptoms;
19. The investigator decides that it is not suitable to participate in this research.

Primary outcomes:
measure: Gastrointestinal bleeding of 6 months in patients with ACS after PCI
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Hefei
country: China
facility: The First Affiliated Hospital of Anhui Medical University
state: Anhui
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
state: Shandong
city: Jining
country: China
facility: The First People's Hospital of Jining City
state: Shandong
city: Liaocheng
country: China
facility: Liaocheng People's Hospital
state: Shandong
city: Linyi
country: China
facility: Linyi City People's Hospital
state: Shandong
city: Qingdao
country: China
facility: Qilu Hospital of Shandong University (Qingdao)
state: Shandong
city: Weihai
country: China
facility: Weihai Central Hospital
state: Shandong
city: Weihai
country: China
facility: Weihai Municipal Hospital
state: Shandong
city: Zibo
country: China
facility: Zibo Central Hospital
state: Shandong
city: Shanghai
country: China
facility: The Ninth People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine
state: Shanghai
Study officials:
affiliation: Qilu Hospital of Shandong University
name: Yu-guo Chen, MD, PhD
role: STUDY_CHAIR
References: