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

Coagulation Clinical Trial

— LOCK  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00794755
• Other study ID #: OHREB #2008555-01H
• Status: Completed
• Phase: Phase 3
• First received: November 18, 2008
• Last updated: July 26, 2011
• Start date: November 2008
• Est. completion date: April 2010

Study information

• Verified date: July 2011
• Source: Ottawa Hospital Research Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Ethics Review Committee
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: April 2010
• Est. primary completion date: April 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Coagulation

Intervention

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.
• 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.

Locations

Country	Name	City	State
Canada	Ottawa Hospital Thrombosis Clinic	Ottawa	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Ottawa Hospital Research Institute

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		At study initiation (for the six month pre-intervention period) and at study completion (after the six-month intervention period)	No
Primary	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		Monthly	No
Secondary	Bleeding Events -- Both major and minor as defined by the International Society on Thrombosis and Haemostasis (ISTH) criteria		Over 6 month study period	Yes
Secondary	Recurrent thrombosis		Over six month study period	Yes