Rivaroxaban or Aspirin in Patients With CHD & GD Undergoing PCI

The Efficacy and Safety of Clopidogrel Combined With Rivaroxaban and Aspirin in Patients With Coronary Heart Disease and Gastrointestinal Diseases Undergoing PCI：a Randomized Controlled Study

The aim of this study is to assess the efficacy and safety of rivaroxaban or aspirin combined with clopidogrel in patients with coronary heart disease and gastrointestinal diseases undergoing PCI.

Study Overview

• Status: Not yet recruiting
• Conditions: Rivaroxaban
• Intervention / Treatment: Drug: clopidogrel combined with rivaroxaban arm

Detailed Description

Background：Aspirin combined with P2Y12 receptor antagonist are the antithrombotic basis of percutaneous coronary intervention (PCI) for coronary heart disease. Guidelines at home and abroad recommend that patients with stable coronary heart disease need double antiplatelet therapy for 6 months, and patients with acute coronary syndrome need double antiplatelet therapy for 12 months to prevent stent thrombosis and reduce the risk of ischemic or atherosclerotic thrombosis events, including stent thrombosis, recurrent myocardial infarction and cardiogenic death. Aspirin can inhibit the activity of cyclooxygenase in gastrointestinal tract, causing gastrointestinal mucosal epithelial injury and bleeding. For patients with gastrointestinal diseases, the risk of bleeding is higher after taking aspirin for a long time. 48.7% of PCI patients suffered from bleeding in digestive tract, so it is very important to protect gastrointestinal mucosa. In the past, patients with coronary heart disease who were accompanied by gastrointestinal diseases and could not tolerate aspirin often delayed PCI or conservative treatment with drugs, and the prognosis was very poor. In the study of patients with coronary heart disease complicated with atrial fibrillation undergoing PCI, it is concluded that the bleeding rate in the clopidogrel combined with rivaroxaban group is lower and the curative effect is not inferior to that of triple antithrombotic regimen. Whether rivaroxaban can replace aspirin for coronary heart disease complicated with gastrointestinal diseases has no research evidence and no relevant guidelines.

Methods:Patients who have been selected will be randomized to the clopidogrel combined with rivaroxaban arm versus the clopidogrel combined with aspirin arm. Patients selected in the clopidogrel combined with rivaroxaban arm will receive clopidogrel 75 mg once daily and rivaroxaban 10 mg once daily. Patients selected in the clopidogrel combined with aspirin arm will receive clopidogrel 75 mg once daily and aspirin 100 mg once daily. The therapy will last for at least six months in the both arms. The primary endpoints will be evaluated at six-months follow-up.

• Study Type: Interventional
• Enrollment (Anticipated): 1020
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient aged from 18 to 75 years
• Patient presents with Non-ST-segment elevation acute coronary syndrome (NSTEMI) combined with GRACE score < 140 points or stable coronary artery disease (SCAD)
• Patient has gastrointestinal diseases (Gastrointestinal diseases are defined as acute or chronic gastritis, erosive gastritis, gastrointestinal bleeding or peptic ulcer healing for 1-12 months, gastrointestinal dysfunction diagnosed by a specialist, and gastrointestinal tumor to be operated on)
• Patient with gastrointestinal bleeding or ulcer in the past one year ago has stomach pain, abdominal distension or other discomfort after taking aspirin, but they can tolerate it
• Patient voluntarily signs informed consent form

Exclusion Criteria:

• Patient presents with Non-ST-segment elevation acute coronary syndrome (NSTEMI) combined with GRACE score >140 points or ST-segment elevation acute myocardial infarction (STEMI)
• Patient with intracranial hemorrhage (within one month) or bleeding of important organs or other than recent surgery for gastrointestinal tumors
• Platelet count <100 000/μL
• Hemoglobin <100g/L
• Patient with active liver diseases or ALT >3 × the upper limit of the normal range or AST>3 × the upper limit of the normal range
• Patient with severe renal insufficiency (eGFR <30ml/min/1.73m2 based on simplified MDRD equation or CrCl <30ml/min based on Cockcroft-Gault equation)
• Patient with active stage of digestive tract ulcer
• Patient with less weight （Weight less than 45kg）
• Allergic to aspirin or rivaroxaban
• Patient has no intention of PCI treatment
• Patient has a malignancy or a life expectancy of less than six months
• Patient is pregnant, breastfeeding, or planning to become pregnant within 6 months
• Patient should take potent CYP3A4 inhibitors and p-gp inhibitors for a long time(such as Ketoconazole, voriconazole, nefazodone, erythromycin)
• Patient should take medium and strong CYP2C19 inhibitors (such as omeprazole, esomeprazole, fluconazole, etc.) or CYP2C19 inducers (such as rifampicin) which are known to interact with clopidogrel for a long time
• Patient is not expected to tolerate six months of medication
• No informed consent can be obtained or any situation that the researcher thinks is not suitable for participating in this study
• Patient is participating in other ongoing clinical studies

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: clopidogrel combined with aspirin arm; Patients selected in the clopidogrel combined with aspirin arm will receive clopidogrel 75 mg once daily and aspirin 100 mg once daily.
Experimental: clopidogrel combined with rivaroxaban arm; Patients selected in the clopidogrel combined with rivaroxaban arm will receive clopidogrel 75 mg once daily and rivaroxaban 10 mg once daily.	Drug: clopidogrel combined with rivaroxaban arm; Patients who have been selected will be randomized to the clopidogrel combined with rivaroxaban arm. clopidogrel 75 mg once daily and rivaroxaban 10 mg once daily; Other Names: clopidogrel combined with rivaroxaban

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of moderate and serve bleeding events which is identified by Bleeding Academic Research Consortium (BARC)	Bleeding Academic Research Consortium (BARC)	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of main adverse cardiovascular and cerebrovascular events (MACCE)	MACCE will include all-cause death, non-fatal stroke, non-fatal myocardial infarction (MI) and ischemia driven revascularization.	6 months

Collaborators and Investigators

• Sponsor: Shenyang Northern Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): March 17, 2021
• Primary Completion (Anticipated): September 16, 2022
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: March 16, 2021
• First Submitted That Met QC Criteria: March 16, 2021
• First Posted (Actual): March 18, 2021

Study Record Updates

• Last Update Posted (Actual): March 18, 2021
• Last Update Submitted That Met QC Criteria: March 16, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Clopidogrel; Rivaroxaban
• Other Study ID Numbers: ShenyangNH

Drug and device information, study documents

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