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

Phase 1

Completed

• Conditions: Anticoagulation
• Interventions: Drug: Warfarin

• Registration Number: NCT01124058
• Lead Sponsor: University of Alberta

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2010-05-13
• Study First Submitted QC: 2010-05-13
• Study First Posted: 2010-05-14
• Study Start: 2010-07
• Primary Completion: 2012-08
• Study Completion: 2012-08
• Status Verified: 2017-10
• Last Update Submitted: 2017-10-24
• Last Update Posted: 2017-10-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 39

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Loading	Warfarin	1.5 times the maintenance dose for 3 days, then resumption of warfarin dosing as per the maintenance dose
Maintenance	Warfarin	Re-start same dose as previously stable on

Primary Outcome Measures

Name	Time	Method
re-starting warfarin "loading" dose vs "maintenance" dose	INR drawn 3 days post-reinitiation and then every 2 days until therapeutic	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.

Secondary Outcome Measures

Name	Time	Method
Compare bleeding/clotting complications between two groups	30 days, 90 days	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.
Compare % of time within, above and below the target INR range	days	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.
Compare the levels of protein C, protein S, and factor II between 2 groups.	week	To compare the levels of protein C, protein S, and factor II between those re-starting warfarin with a "loading" dose or "maintenance" dose.

Trial Locations

Locations (1)

Univeristy of Alberta; 🇨🇦 Edmonton, Alberta, Canada