Evaluation of Maintenance Dosing vs Loading Dosing Upon Restarting Warfarin Therapy: A Prospective Randomized Trial

Study Overview
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Brief Summary
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A prospective, randomized trial to compare the time taken to achieve a therapeutic INR upon re-starting warfarin at a loading dose (namely 1.5 times the maintenance dose for 3 days) compared to the known maintenance dose.

Detailed Description
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Patients will be identified via the University of Alberta Hospital Anticoagulation Management Service. Following the receipt of written, informed consent, patients will be randomized to re-start warfarin at their maintenance dose or at a loading dose (1.5 times the maintenance dose for 3 days, then resumption of warfarin dosing as per the maintenance dose). Randomization will be performed on-line through the EPICORE Centre. Assuming Day 1 is the day warfarin is re-started, patients will have INRs done on day 3 and at least every 2 days thereafter until a therapeutic INR is obtained. In addition, protein C, protein S and factor II levels will be obtained while the patient is on stable maintenance dosing of warfarin (i.e., prior to holding warfarin for the procedure), 7 days after re-starting warfarin, and 14 days after re-starting warfarin. Complete blood counts (CBCs) will be done with each INR if the patient is taking a low molecular weight heparin (LMWH). Patients will have their anticoagulant therapy managed by the AMS for 6 weeks and will receive a telephone follow-up by the AMS at 90 days to determine if any bleeding or clotting complications occurred.

Official Title
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Evaluation of Maintenance Dosing vs Loading Dosing Upon Restarting Warfarin Therapy: A Prospective Randomized Trial.

Conditions
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Anticoagulation

Intervention / Treatment
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* Drug: warfarin
* Drug: Warfarin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have 'stable warfarin maintenance dosing' (defined as last 2 INRs within therapeutic range with weekly warfarin dosing not being changed any more than 10%) Have an INR indicative of not taking any warfarin (INR <1.4) or confirmation of the patient not taking any warfarin in the past 4 days Provide written, informed consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Loading<br>1.5 times the maintenance dose for 3 days, then resumption of warfarin dosing as per the maintenance dose | Drug: warfarin<br>* Patients will be randomized to re-start warfarin at their maintenance dose or at a loading dose (1.5 times the maintenance dose for 3 days, then resumption of warfarin dosing as per the maintenance dose).<br>* Other names: warfarin, Taro-warfarin, Apo-warfarin, Coumadin, Fragmin, Low-molecular weight heparin;|
| Active Comparator: Maintenance<br>Re-start same dose as previously stable on | Drug: Warfarin<br>* Maintenance dose is the amount of warfarin that a patient required to maintain a therapeutic INR.<br>* Other names: warfarin, Taro-warfarin, Apo-warfarin, Coumadin, Fragmin, Low-molecular weight heparin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| re-starting warfarin loading dose vs maintenance dose | To compare the time taken to achieve a therapeutic INR between those patients re-starting warfarin with a loading dose and a maintenance dosing regimen using linear interpolation of INRs. | INR drawn 3 days post-reinitiation and then every 2 days until therapeutic | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare % of time within, above and below the target INR range | To compare the % of time within, above and below the desired INR range between those patients re-starting warfarin with a loading dose or maintenance dose 6 weeks following restarting warfarin. | days | 
| Compare bleeding/clotting complications between two groups | To compare the rates of thrombosis (i.e., stroke) / major hemorrhage between those re-starting warfarin with a loading dose or maintenance dose at 30 days and 90 days following restarting warfarin. | 30 days, 90 days | 
| Compare the levels of protein C, protein S, and factor II between 2 groups. | To compare the levels of protein C, protein S, and factor II between those re-starting warfarin with a loading dose or maintenance dose. | week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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restarting warfarin, time to therapeutic INR