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
Full Title of Study: “Evaluation of Warfarin Initiation at 3mg Versus 5mg for Anticoagulation of Mechanical Mitral Valve Replacement Patients”
- Study Type: Interventional
- Study Design
- Allocation: Randomized
- Intervention Model: Parallel Assignment
- Primary Purpose: Treatment
- Masking: Single (Outcomes Assessor)
- Study Primary Completion Date: January 1, 2019
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Blood samples were withdrawn from patients for evaluation of INR.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.
- Drug: Warfarin Sodium 5 MG
- warfarin sodium 5mg tablets
- Drug: Warfarin Sodium 3 MG
- warfarin sodium 3mg tablets
- 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.
Arms, Groups and Cohorts
- Experimental: 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.
- Experimental: 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.
Clinical Trial Outcome Measures
- Efficacy of warfarin initiating dose and the corresponding dosing schedule: Time to reach therapeutic INR range (TTR)
- Time Frame: 4-16 days
- Time to reach therapeutic INR range (TTR):The time in days required for the patient from the start of warfarin initiation till reaching the therapeutic
- Evaluation of overanticoagulation
- Time Frame: from 3 to 5 days
- Proportion of patients who achieved the target INR of 2.0-3.0 between day 3 and day 5
- Anticoagulation Safety evaluation
- Time Frame: from 4 to 16 days
- Incidence of major and minor bleeding events
- Low Molecular Weight Heparin consumption
- Time Frame: from 4 to 16 days
- The total dose of enoxaparin in mg that the patient received till discontinuation of bridging
- The Overall cost evaluation
- Time Frame: from 4 to 16 days
- total cost spent in LE during the follow up period calculated by the summation of the cost of treatment , cost of bleeding event management and cost of hospital stay.
Participating in This Clinical Trial
- New mechanical mitral valve prostheses patients who will receive anticoagulation with warfarin with the use of enoxaparen as a bridging agent.
- 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
- Impaired nutritional status
- Alcohol abuse
Gender Eligibility: All
Minimum Age: 18 Years
Maximum Age: 60 Years
Are Healthy Volunteers Accepted: No
- Lead Sponsor
- Sarah Sabry Hashem
- Provider of Information About this Clinical Study
- Sponsor-Investigator: Sarah Sabry Hashem, Msc, Clinical Pharmacy – Ain Shams University
- Overall Official(s)
- Ayman M Saleh, MD, Study Director, Ain Shams University Hospitals
- Lamiaa M ElWakeel, PhD, Study Director, Faculty of pharmacy Ain Shams University
- Marwa A Ahmed, PhD, Study Director, Faculty of pharmacy Ain Shams University
- Sarah S Hashem, Msc, Principal Investigator, The Cardiovascular Hospital Ain Shams University
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