RIvoraxaban in Mitral Stenosis — RISE MS  

Atrial Fibrillation Clinical Trial

Official title: RIvoraxaban Safety and Efficacy in Patients With Mitral Stenosis

Status Terminated

Clinical Trial Summary

In this randomized controlled clinical trial, patients with moderate to severe mitral valve stenosis (MS) and atrial fibrillation (AF) will be enrolled into the study.Participants will be divided into two groups based on the anticoagulation regimen type. The intervention group will receive rivaroxaban and the control group will be given warfarin. All patients will be observed closely during a period of one year. Through the follow up, embolic events and hemorrhagic complications will be recorded in both groups. In addition, patients in both group will undergo a baseline magnetic resonance imaging (MRI) and an MRI after one-year follow up, by which the silent embolic events will be compared in both groups.

Clinical Trial Description

Study rationale:

Since the introduction of warfarin as the main oral anticoagulation therapy in patients with MS and AF, no other drug has been replaced/suggested by any medical community for this group of patients. Warfarin is considered a drug with marginal therapeutic effect, with a need for constant monitoring, with lots of known drug interaction and finally a great probability of adverse complication. Novel oral anticoagulation agents have resolved several of these drawbacks and has been recommended as a viable option as a substitute of warfarin in various clinical scenario. Until now, no trial has evaluated the potentiality of using novel oral anticoagulations (NOACs) in patients with MS accompanied by AF. In this trial investigators are intended to elaborate the efficacy and safety of rivaroxaban in patients with MS complicated by AF

Background:

Since the introduction of NOAC, their indication has been expanded in various type of diseases. From protecting against ischemic stroke in AF patients to treatment of venous thromboembolism (VTE) events, NOAC were both safe and effective compared to warfarin. Importantly this new class of drug have omitted some of the major drawbacks of warfarin; their predictable therapeutic level has permitted to prescribed them as fixed dosage without constant laboratory tests. Also their shorter half-life has made critical situation in which reversal of anticoagulation agents were needed, more manageable.

There are solid evidences that AF is one of the major cause of cerebrovascular ischemic events, and anticoagulation therapy by decreasing thrombus formation reduces significantly these major adverse events. So there is no wonder that first studies on NOAC were performed on AF population. In the beginning AF caused by valvular heart diseases were judge to bear a much greater risk as cerebrovascular events are concerns, and consequently patients with valvular pathologies were eliminated from the earlier pivotal studies. However, through these years, there are lots of evidences showing the safety and efficacy of NOAC in valvular pathologies. Recently ENGAGE TIMI 48 Trial has showed the efficacy and safety of Edoxaban in patients with valvular heart diseases. By testing the theory in a large population, the ENGAGE TIMI 48 study emphasized on a greater risk of embolic events in patients with VHD and AF, but this increasing risk has no effect on the efficacy of edoxaban compared to warfarin. Interestingly the new agents had less major bleeding compared to warfarin.

But still in all these trials, moderate to severe MS and mechanical prosthetic valves were omitted from the studied population. The rationale behind this omission was the significant higher risk of thrombosis in the two mentioned subgroups. However, investigators have several hypotheses that patients with MS are different from patients undergoing mechanical prosthetic valve replacement:

• Although there is a higher risk of thromboembolic events in MS comparing to other valvular heart diseases, this has not resulted in increasing the magnitude of protection with warfarin; the recommended levels of international normalized ratio (INR) in MS population is 2-3 as other pathologies.

• Apart from patients with mechanical prosthesis implanted in mitral valve position, there is no other subgroup of patients whom higher INR and level of anticoagulation with warfarin proved to be more efficacious.

In conclusion, investigators think that the MS population might be a good target for NOAC and as other valvular heart disease, they could benefit from the advantages of these drugs. ;

Related Conditions & MeSH terms

• Anticoagulant Adverse Reaction
• Atrial Fibrillation
• Constriction, Pathologic
• Heart Diseases
• Mitral Stenosis
• Mitral Valve Stenosis
• Rheumatic Heart Disease

• NCT number: NCT03926156
• Study type: Interventional
• Source: Rajaie Cardiovascular Medical and Research Center
• Status: Terminated
• Phase: Phase 3
• Start date: May 22, 2019
• Completion date: August 14, 2021