Official Title: “A Phase III Pilot RCT (Randomized, Controlled Trial) to Assess the Effectiveness of Low Dose Vitamin K1 (200 Micrograms Per Day) on Improving Anticoagulation Control in Unstable Patients on Warfarin”

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: November 2009

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.

Intervention(s) in this Clinical Trial

• Dietary Supplement: Vitamin K1 (Phytonadione)
  • Vitamin K1 tablets (100 micrograms per tablet) will be taken by patients randomized to the Vitamin K arm. Dosage is two tablets per day (200 micrograms per day) to be taken with warfarin for the 6 month study period.
• Dietary Supplement: Placebo
  • Lactose-based placebo tablets (identical in appearance to the Vitamin K1 tablets) will be taken by patients randomized to the placebo arm. Dosage is two tablets per day to be taken with warfarin for the 6 month study period.

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: Vitamin K
• Placebo Comparator: Placebo

Primary Measures

• 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 changes
  • Time Frame: At study initiation (for the six month pre-intervention period) and at study completion (after the six-month intervention period)
    Safety Issue?: No
• 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-up
  • Time Frame: Monthly
    Safety Issue?: No

Secondary Measures

• Bleeding Events -- Both major and minor as defined by the International Society on Thrombosis and Haemostasis (ISTH) criteria
  • Time Frame: Over 6 month study period
    Safety Issue?: Yes
• Recurrent thrombosis
  • Time Frame: Over six month study period
    Safety Issue?: Yes

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Ottawa Health Research Institute

Overall Clinical Trial Officials and Contacts

Philip S Wells, MD, MSc Principal Investigator Ottawa Hospital, Ottawa Health Research Institute  

Overall Contact: Habeeb Majeed, BSc, MSc(c) 613-798-5555 hmajeed@ohri.ca

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00794755

Study ID Number: OHREB #2008555-01H

ClinicalTrials.gov Identifier: NCT00794755

Health Authority: Canada: Ethics Review Committee