RIvoraxaban in Mitral Stenosis

NCT03926156 | Terminated Phase 3 DMC

• 1 other identifier: 962426
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Mitral Stenosis; Rheumatic Heart Disease; Atrial Fibrillation; Anticoagulant Adverse Reaction

Outcome Measures

Primary Outcomes (2)

• Number of participants with stroke

  A stroke is defined as an abrupt onset, over minutes to hours, of a focal neurological deficit in the distribution of a single brain artery that is not due to an identifiable nonvascular cause (i.e., brain tumor or trauma), and that either lasts at least 24 hours or results in death within 24 hours of onset.

  12 months

• Number of participants with systemic embolic event

  An SEE is defined as an arterial embolism resulting in clinical ischemia, excluding the central nervous system (CNS), coronary and pulmonary arterial circulation.

  12 months

Secondary Outcomes (1)

• Number of participants with bleeding complications

  12 months

Study Arms (2)

Rivaroxaban

EXPERIMENTAL

Rivaroxaban will be used as the anticoagulation drug for the intervention group. Rivaroxaban is an anticoagulant and the first orally active direct factor Xa inhibitor. Unlike warfarin, routine lab monitoring of INR is not necessary. However there is no approved antidote available in the event of a major bleed. Only the 10 mg tablet can be taken without regard to food. The 15 mg and 20 mg tablet should be taken with food.

Drug: Rivaroxaban

Warfarin

ACTIVE COMPARATOR

Warfarin will be used as the anticoagulation drug for the control group. Warfarin decreases blood clotting by blocking an enzyme called vitamin K epoxide reductase that reactivates vitamin K1. Without sufficient active vitamin K1, clotting factors II, VII, IX, and X have decreased clotting ability. The anticlotting protein C and protein S are also inhibited but to a lesser degree. A few days are required for full effect to occur and these effects can last for up to five days, and the final dose will be adjusted according to PT and related INR.

Drug: Warfarin

Interventions

Rivaroxaban DRUG

Rivaroxaban will be used as the anticoagulation drug for the intervention group. Rivaroxaban is an anticoagulant and the first orally active direct factor Xa inhibitor. Unlike warfarin, routine lab monitoring of INR is not necessary. However there is no approved antidote available in the event of a major bleed. Only the 10 mg tablet can be taken without regard to food. The 15 mg and 20 mg tablet should be taken with food

Rivaroxaban

Warfarin DRUG

Warfarin will be used as the anticoagulation drug for the control group. Warfarin decreases blood clotting by blocking an enzyme called vitamin K epoxide reductase that reactivates vitamin K1. Without sufficient active vitamin K1, clotting factors II, VII, IX, and X have decreased clotting ability. The anticlotting protein C and protein S are also inhibited but to a lesser degree. A few days are required for full effect to occur and these effects can last for up to five days, and the final dose will be adjusted according to PT and related INR.

Warfarin

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Men and women ≥ 18 year-old
• Diagnosed with moderate to severe mitral stenosis who have a history of AF of any duration documented by any electrical tracing within the prior 12 months and for which anticoagulation is indicated and planned for the duration of the study.
• Ability to take oral medication and be willing to adhere to the rivaroxaban regimen

You may not qualify if:

• Left atrial clot
• Severe renal dysfunction (creatinine clearance \[CrCl\] \<15 mL/min), subjects with
• A condition associated with a high risk of bleeding
• Allergic to rivaroxabn/warfarin

Sponsors & Collaborators

• Rajaie Cardiovascular Medical and Research Center: lead
• National Institute for Medical research and Development (NIMAD): collaborator
• Abidi Pharmaceuticals: collaborator

Study Sites (1)

Rajaie Cardiovascular Medical and Research Center

Tehran, 1995614331, Iran

Location

Related Publications (1)

• Sadeghipour P, Pouraliakbar H, Parsaee M, Shojaeifard M, Farrashi M, JamalKhani S, Tashakori Beheshti A, Rostambeigi S, Ebrahimi Meimand S, Firouzi A, Peighambari MM, Alemzadeh-Ansari MJ, Haghjoo M, Noohi F, Maleki M, De Caterina R. RIvaroxaban in mitral stenosis (RISE MS): A pilot randomized clinical trial. Int J Cardiol. 2022 Jun 1;356:83-86. doi: 10.1016/j.ijcard.2022.03.037. Epub 2022 Mar 16.

  PMID: 35306032 DERIVED

MeSH Terms

Conditions

Mitral Valve Stenosis; Rheumatic Heart Disease; Atrial Fibrillation

Interventions

Rivaroxaban; Warfarin

Condition Hierarchy (Ancestors)

Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases; Rheumatic Fever; Streptococcal Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Arrhythmias, Cardiac; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; 4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Majid Maleki, M.D.

  Rajaie Cardiovascular Medical and Research Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2019
• First Posted: April 24, 2019
• Study Start: May 22, 2019
• Primary Completion: May 22, 2021
• Study Completion: August 14, 2021
• Last Updated: August 19, 2021

Record last verified: 2021-08

Locations

IR (1)