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Low Dose Supplementation to Improve Anticoagulation Control With Oral Vitamin K as an Adjuvant to Warfarin Therapy

Phase 3
Completed
Conditions
Coagulation
Interventions
Dietary Supplement: Vitamin K1 (Phytonadione)
Dietary Supplement: Placebo
Registration Number
NCT00794755
Lead Sponsor
Ottawa Hospital Research Institute
Brief Summary

The main objective of this study is to assess the effectiveness of low dose Vitamin K1 (200 micrograms per day) at improving anticoagulation control in unstable patients on warfarin. This study will also aim to look at effectiveness in the context of genes known to influence warfarin metabolism, variability in the consumption of Vitamin K rich foods, and patient knowledge about warfarin anticoagulation -- factors which have been associated with anticoagulation control and which can influence the effectiveness of this intervention in clinical practice.

Detailed Description

A double-blinded placebo controlled pilot RCT assessing the effectiveness of daily supplementation with low dose Vitamin K1 (200 micrograms per day) against placebo at improving anticoagulation control. Previous studies assessing the efficacy of this intervention have been small and further trials are required to evaluate the true effectiveness and safety profile. Furthermore the impact of genetic polymorphisms, known to impact warfarin metabolism, on the effectiveness/safety of this intervention will also be assessed in this study. Demographic and clinical variables as well as potential confounding variables such as variable dietary Vitamin K intake, concomitant interacting medications, and anticoagulation knowledge will be assessed in this study. Given that this is a pilot study we will be looking at recruitment numbers and necessary parameter estimates to determine the number of patients available at our institution for the study. Power analysis will be performed to evaluate the treatment effect size between the placebo and intervention groups.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
100
Inclusion Criteria
  • >= 18 years old
  • Have been on warfarin anticoagulation for at least 9 months
  • Have an INR target range of 2.0-3.0
  • Have "unstable" anticoagulation control, defined as in the preceding 6 months having at least 3 INRs out of range (>= 3.2 or =<1.8) or at least 3 warfarin dose changes
  • Have anticoagulation managed by the Ottawa Hospital Thrombosis Clinic
  • Able to provide written, informed consent
Exclusion Criteria
  • Anticipated interruption or termination of warfarin anticoagulation in the next six months for a period of 1 week or greater
  • Patient instability in the preceding six months suspected to be due to a) Interruption of warfarin therapy for a period of 1 week or more or b) Significant non-compliance (assessed from patient record)
  • Possess a known allergy to Vitamin K or lactose based placebos
  • Unable/Refusal to provide written, informed consent

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Vitamin KVitamin K1 (Phytonadione)-
PlaceboPlacebo-
Primary Outcome Measures
NameTimeMethod
Anticoagulation control -- Point estimates (and standard deviations) for the following variables: Percent time in therapeutic range, standard deviation of INRs, number of INRs outside of therapeutic range, and number of dose changesAt study initiation (for the six month pre-intervention period) and at study completion (after the six-month intervention period)
Recruitment Numbers -- Number of patients deemed eligible, Number of patients solicited, Number of patients screened, Number of patients enrolled, and Number of enrolled patients lost to follow-upMonthly
Secondary Outcome Measures
NameTimeMethod
Bleeding Events -- Both major and minor as defined by the International Society on Thrombosis and Haemostasis (ISTH) criteriaOver 6 month study period
Recurrent thrombosisOver six month study period

Trial Locations

Locations (1)

Ottawa Hospital Thrombosis Clinic

🇨🇦

Ottawa, Ontario, Canada

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