The Effect of Dual Eradication Therapy vs PPI on Gastrointestinal Bleeding in ACS Patients

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Coronary Syndrome; Helicobacter Pylori Infection
• Intervention / Treatment: Drug: Vonoprazan-based dual eradication therapy for two weeks; Drug: amoxicillin; Drug: Pantoprazole

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.

• Study Type: Interventional
• Enrollment (Anticipated): 2600
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Yuan Bian, MD, PhD; Phone Number: +8618560083065; Email: bianyuan@sdu.edu.cn

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230000
      • The First affiliated Hospital of Anhui Medical University
      • Contact: xianhe lin
  • Shandong
    • Jinan, Shandong, China, 250012
      • Qilu Hospital of Shandong University
      • Contact: YUGUO CHEN
    • Jining, Shandong, China, 272000
      • The First People's Hospital of Jining City
      • Contact: shuyin sun
    • Liaocheng, Shandong, China, 252000
      • Liaocheng People's hospital
      • Contact: yuzeng xue
    • Linyi, Shandong, China, 276000
      • Linyi City People's Hospital
      • Contact: yanjin wei
    • Qingdao, Shandong, China, 266000
      • Qilu Hospital of Shandong University (Qingdao)
      • Contact: beian you
    • Weihai, Shandong, China, 264200
      • Weihai Central Hospital
    • Weihai, Shandong, China, 264200
      • Weihai Municipal Hospital
      • Contact: xinfu zhou
    • Zibo, Shandong, China, 255000
      • Zibo central Hospital
  • Shanghai
    • Shanghai, Shanghai, China, 200000
      • The Ninth People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine
      • Contact: changqian wang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vonoprazan-based dual eradication therapy; 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 course of 14 days .	Drug: Vonoprazan-based dual eradication therapy for two weeks; Patients with ACS after PCI, associated with positive Hp need a long-term DAPT treatment. We conducted a study on the prevention of gastrointestinal bleeding between vonoprazan-based dual eradication therapy for two weeks and pantoprazole for six months of a rountine therapy.; Drug: amoxicillin; amoxicillin
Active Comparator: Pantoprazole; To take pantoprazole 40 mg daily, followed up to 6 months after randomization.	Drug: Pantoprazole; Pantoprazole

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gastrointestinal bleeding of 6 months in patients with ACS after PCI	To compare the effects of the combination of vonoprazan + amoxicillin and pantoprazole on gastrointestinal bleeding events within 6 months in patients with ACS after PCI，The primary endpoint was gastrointestinal bleeding, including gastroduodenal bleeding, gastrointestinal bleeding with unknown bleeding site, and occult gastrointestinal bleeding.	6 months

Collaborators and Investigators

• Sponsor: Qilu Hospital of Shandong University
• Investigators: Study Chair: Yu-guo Chen, MD, PhD, Qilu Hospital of Shandong University

Study record dates

Study Major Dates

• Study Start (Anticipated): August 10, 2021
• Primary Completion (Anticipated): January 30, 2023
• Study Completion (Anticipated): June 30, 2023

Study Registration Dates

• First Submitted: January 20, 2021
• First Submitted That Met QC Criteria: January 27, 2021
• First Posted (Actual): January 28, 2021

Study Record Updates

• Last Update Posted (Actual): August 3, 2021
• Last Update Submitted That Met QC Criteria: August 2, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Gastrointestinal Diseases; Hemorrhage; Infections; Acute Coronary Syndrome; Gastrointestinal Hemorrhage; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Bacterial Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Amoxicillin; Pantoprazole
• Other Study ID Numbers: 2020SDUCRCA006

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No