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

Sponsor

University of Alberta (Other)

Overall Status

Completed

CT.gov ID

NCT01124058

Collaborator

(none)

Enrollment

Location

Arms

Actual Duration (Months)

1.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Anticoagulation	Drug: warfarin Drug: Warfarin	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

39 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jul 1, 2010

Actual Primary Completion Date :

Aug 1, 2012

Actual Study Completion Date :

Aug 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Loading 1.5 times the maintenance dose for 3 days, then resumption of warfarin dosing as per the maintenance dose	Drug: warfarin 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). Other Names: warfarin, Taro-warfarin, Apo-warfarin, Coumadin, Fragmin, Low-molecular weight heparin
Active Comparator: Maintenance Re-start same dose as previously stable on	Drug: Warfarin "Maintenance" dose is the amount of warfarin that a patient required to maintain a therapeutic INR. Other Names: warfarin, Taro-warfarin, Apo-warfarin, Coumadin, Fragmin, Low-molecular weight heparin

Arm

Intervention/Treatment

Experimental: Loading

1.5 times the maintenance dose for 3 days, then resumption of warfarin dosing as per the maintenance dose

Drug: warfarin

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).

Other Names:

warfarin, Taro-warfarin, Apo-warfarin, Coumadin, Fragmin, Low-molecular weight heparin

Active Comparator: Maintenance

Re-start same dose as previously stable on

Drug: Warfarin

"Maintenance" dose is the amount of warfarin that a patient required to maintain a therapeutic INR.

Other Names:

warfarin, Taro-warfarin, Apo-warfarin, Coumadin, Fragmin, Low-molecular weight heparin

Outcome Measures

Primary Outcome Measures

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

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 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 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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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