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

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

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.

Study Overview

• Status: Completed
• Conditions: Anticoagulation
• Intervention / Treatment: Drug: warfarin; Drug: Warfarin

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 Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2C8
      • Univeristy of Alberta

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Alberta
• Investigators: Principal Investigator: Tammy J Bungard, BSP, PharmD, Univeristy of Alberta; Principal Investigator: Bruce Ritchie, MD, FRCPC, University of Alberta

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 1, 2010
• Primary Completion (ACTUAL): August 1, 2012
• Study Completion (ACTUAL): August 1, 2012

Study Registration Dates

• First Submitted: May 13, 2010
• First Submitted That Met QC Criteria: May 13, 2010
• First Posted (ESTIMATE): May 14, 2010

Study Record Updates

• Last Update Posted (ACTUAL): October 25, 2017
• Last Update Submitted That Met QC Criteria: October 24, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: restarting warfarin; time to therapeutic INR
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Heparin; Calcium heparin; Heparin, Low-Molecular-Weight; Tinzaparin; Dalteparin; Warfarin
• Other Study ID Numbers: 2007UHFMDvsLD