Warfarin Initiation in Mechanical Mitral Valve Replacement Patients

NCT ID: NCT04235569

Last Updated: 2020-01-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-01
• Study Completion Date: 2019-09-01

Brief Summary

A prospective, comparative study evaluating warfarin initiation in a dose of 3mg versus 5mg in mechanical mitral valve prostheses patients who received anticoagulation with warfarin with the use of enoxaparen as a bridging agent .Fifty patients were included and compared in terms of the primary outcome time to reach therapeutic INR range.Other outcomes includes proportion of patients who achieved the target INR of 2.0-3.0 between day 3 and day 5, total dose of enoxaparin required for bridging, safety related to both doses of anticoagulants used

Detailed Description

Inpatients of The Cardiovascular hospital who had undergone mitral heart valve replacement with a mechanical prosthesis and commencing warfarin were eligible for inclusion. Patients were included after they had newly undergone elective surgery for implantation of mechanical mitral heart valves, had commenced on warfarin, received enoxaparin as a bridging agent and had INR monitored for a minimum of 4 consecutive days after warfarin initiation.

A total of 50 consecutive MVR patients were recruited. Each was assigned to either the group I (25 patients) or the group II (25 patients) group. All patients received the conventional postoperative treatment including: Diuretics, beta-blockers, digoxin or heart rate-regulating calcium channel blockers and anticoagulation bridging therapy using LMWH according to the European Society of Cardiology (ESC) Guidelines for the management of MVR and antibiotic for 48hour after surgery according to the investigator's hospital's antibiotic protocol.

Baseline evaluation included demographics and history taking. After obtaining the informed consent, information including age, weight, height, smoking state, and other diseases e.g. hypertension, diabetes, hyperlipidemias, etc. were documented for each patient. Medication history in details, as well as the background cardiovascular treatment was considered.

Blood samples were withdrawn from patients for evaluation of INR. Complete blood count, kidney and liver function tests were performed as part of the routine admission care.

All patients were followed up daily post operative till reaching an in range INR value. All patients were observed daily for INR values and dose adjusted accordingly and also estimation of incidence and severity of bleeding complications was done.

Conditions

Mitral Valve Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Group I

a group of 25 patients received 5mg Marevan ® tablets as initiation warfarin dose in combination of enoxaparin (Clexane® ) as a bridging agent.INR was monitored daily and dose adjustments were done to reach therapeutic INR range (2-3) at which the Enoxaparen was discontinued.Follow up was continued till first INR reading in therapeutic range.

Bleeding events due to overanticoagulation were monitored through the follow up period.

Group Type: EXPERIMENTAL

Warfarin Sodium 5 MG

Intervention Type: DRUG

warfarin sodium 5mg tablets

Enoxaparin Sodium 100 MG/ML Prefilled Syringe

Intervention Type: DRUG

Clexane® Syringes 2,000 IU (20 mg)/0.2 ml solution for injection in pre-filled syringes.

Clexane® Syringes 4,000 IU (40 mg)/0.4 ml solution for injection in pre-filled syringes.

Clexane® Syringes 6,000 IU (60 mg)/0.6 ml solution for injection in pre-filled syringes.

Clexane® Syringes 8,000 IU (80 mg)/0.8 ml solution for injection in pre-filled syringes.

Dose was determined individually for each patient as 1mg/kg every 12 hours.

Group II

a group of 25 patients received 3mg Marevan ® tablets as initiation warfarin dose in combination of enoxaparin (Clexane® ) as a bridging agent.INR was monitored daily and dose adjustments were done to reach therapeutic INR range (2-3) at which the Enoxaparen was discontinued.Follow up was continued till first INR reading in therapeutic range.

Bleeding events due to overanticoagulation were monitored through the follow up period.

Group Type: EXPERIMENTAL

Warfarin Sodium 3 MG

Intervention Type: DRUG

warfarin sodium 3mg tablets

Enoxaparin Sodium 100 MG/ML Prefilled Syringe

Intervention Type: DRUG

Clexane® Syringes 2,000 IU (20 mg)/0.2 ml solution for injection in pre-filled syringes.

Clexane® Syringes 4,000 IU (40 mg)/0.4 ml solution for injection in pre-filled syringes.

Clexane® Syringes 6,000 IU (60 mg)/0.6 ml solution for injection in pre-filled syringes.

Clexane® Syringes 8,000 IU (80 mg)/0.8 ml solution for injection in pre-filled syringes.

Dose was determined individually for each patient as 1mg/kg every 12 hours.

Interventions

Warfarin Sodium 5 MG

warfarin sodium 5mg tablets

Intervention Type: DRUG

Warfarin Sodium 3 MG

warfarin sodium 3mg tablets

Intervention Type: DRUG

Enoxaparin Sodium 100 MG/ML Prefilled Syringe

Clexane® Syringes 2,000 IU (20 mg)/0.2 ml solution for injection in pre-filled syringes.

Clexane® Syringes 4,000 IU (40 mg)/0.4 ml solution for injection in pre-filled syringes.

Clexane® Syringes 6,000 IU (60 mg)/0.6 ml solution for injection in pre-filled syringes.

Clexane® Syringes 8,000 IU (80 mg)/0.8 ml solution for injection in pre-filled syringes.

Dose was determined individually for each patient as 1mg/kg every 12 hours.

Intervention Type: DRUG

Other Intervention Names

Marevan 5mg; Marevan 3mg; Clexane

Eligibility Criteria

Inclusion Criteria

• New mechanical mitral valve prostheses patients who will receive anticoagulation with warfarin with the use of enoxaparen as a bridging agent.

Exclusion Criteria

• Pregnant or lactating women
• Renal disorder (GFR = 45< mL/min) or patients on renal dialysis
• Hepatic disorder (Child Pugh class B or C)
• Clinically significant active bleeding.
• Recurrent DVT or PE.
• Baseline INR >1.2
• Asian ancestry
• Cancer
• Impaired nutritional status
• Alcohol abuse

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sarah Sabry Hashem

OTHER

Sponsor Role: lead

Responsible Party

Sarah Sabry Hashem

Msc, Clinical Pharmacy

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Ayman M Saleh, MD

Role: STUDY_DIRECTOR

Ain Shams University

Lamiaa M ElWakeel, PhD

Role: STUDY_DIRECTOR

Faculty of pharmacy Ain Shams University

Marwa A Ahmed, PhD

Role: STUDY_DIRECTOR

Faculty of pharmacy Ain Shams University

Sarah S Hashem, Msc

Role: PRINCIPAL_INVESTIGATOR

The Cardiovascular Hospital Ain Shams University

Locations

The Cardiovascular Hospital

Heliopolis, Cairo Governorate, Egypt

Countries

Egypt

References

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Sabry S, El Wakeel LM, Saleh A, Ahmed MA. Comparison of Warfarin Initiation at 3 mg Versus 5 mg for Anticoagulation of Patients with Mechanical Mitral Valve Replacement Surgery: A Prospective Randomized Trial. Clin Drug Investig. 2022 Apr;42(4):309-318. doi: 10.1007/s40261-022-01137-7. Epub 2022 Mar 10.

Reference Type: DERIVED

PMID: 35274222 (View on PubMed)

Other Identifiers

11222

Identifier Type: -

Identifier Source: org_study_id