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

• ClinicalTrials.gov Identifier: NCT01124058
• Recruitment Status: Completed
• First Posted: May 14, 2010
• Last Update Posted: October 25, 2017
• Sponsor: University of Alberta
• Information provided by (Responsible Party): Tammy Bungard, University of Alberta

Tracking Information

• First Submitted Date: May 13, 2010
• First Posted Date: May 14, 2010
• Last Update Posted Date: October 25, 2017
• Actual Study Start Date: July 2010
• Actual Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 13, 2010)

re-starting warfarin "loading" dose vs "maintenance" dose [ Time Frame: 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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 13, 2010)

• Compare % of time within, above and below the target INR range [ Time Frame: 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 [ Time Frame: 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. [ Time Frame: 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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Evaluation of Maintenance Dosing vs Loading Dosing Upon Restarting Warfarin Therapy: A Prospective Randomized Trial
• Official Title: Evaluation of Maintenance Dosing vs Loading Dosing Upon Restarting Warfarin Therapy: A Prospective Randomized Trial.
• 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 Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Anticoagulation

Intervention

• 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 Name: warfarin, Taro-warfarin, Apo-warfarin, Coumadin, Fragmin, Low-molecular weight heparin
• Drug: Warfarin
  "Maintenance" dose is the amount of warfarin that a patient required to maintain a therapeutic INR.
  Other Name: warfarin, Taro-warfarin, Apo-warfarin, Coumadin, Fragmin, Low-molecular weight heparin

Study Arms

• Experimental: Loading
  1.5 times the maintenance dose for 3 days, then resumption of warfarin dosing as per the maintenance dose
  Intervention: Drug: warfarin
• Active Comparator: Maintenance
  Re-start same dose as previously stable on
  Intervention: Drug: Warfarin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 24, 2017): 39
• Original Estimated Enrollment (submitted: May 13, 2010): 40
• Actual Study Completion Date: August 2012
• Actual Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada

Administrative Information

• NCT Number: NCT01124058
• Other Study ID Numbers: 2007UHFMDvsLD
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Tammy Bungard, University of Alberta
• Study Sponsor: University of Alberta
• Collaborators: Not Provided

Investigators

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

• PRS Account: University of Alberta
• Verification Date: October 2017