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

Sponsor:	Ottawa Hospital Research Institute
Information provided by:	Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier:	NCT00794755

Purpose

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.

Condition	Intervention	Phase
Coagulation	Dietary Supplement: Vitamin K1 (Phytonadione) Dietary Supplement: Placebo	Phase 3

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

Resource links provided by NLM:

MedlinePlus related topics: Blood Thinners Vitamin K

Drug Information available for: Menadione Warfarin Phytonadione Warfarin sodium Vitamin K1

U.S. FDA Resources

Further study details as provided by Ottawa Hospital Research Institute:

Primary Outcome 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) ] [ Designated as 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 ] [ Designated as safety issue: No ]

Secondary Outcome 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 ] [ Designated as safety issue: Yes ]
Recurrent thrombosis [ Time Frame: Over six month study period ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	100
Study Start Date:	November 2008
Study Completion Date:	April 2010
Primary Completion Date:	April 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Vitamin K	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 Comparator: Placebo	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.

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00794755

Locations

Canada, Ontario
Ottawa Hospital Thrombosis Clinic
Ottawa, Ontario, Canada, K1Y4E9

Sponsors and Collaborators

Ottawa Hospital Research Institute

Investigators

Principal Investigator:

Philip S Wells, MD, MSc

Ottawa Hospital, Ottawa Health Research Institute

More Information

No publications provided

Responsible Party:	Dr. Philip S Wells (Chair, Department of Medicine), Ottawa Hospital Research Institute (OHRI)
ClinicalTrials.gov Identifier:	NCT00794755 History of Changes
Other Study ID Numbers:	OHREB #2008555-01H
Study First Received:	November 18, 2008
Last Updated:	July 26, 2011
Health Authority:	Canada: Ethics Review Committee

Keywords provided by Ottawa Hospital Research Institute:

Vitamin K
Vitamin K1 (Phytonadione)
Unstable INR
VTE or Thrombosis

Warfarin
Anticoagulation Control
Patients on warfarin with unstable anticoagulation control

Additional relevant MeSH terms:

Vitamin K 1
Vitamin K
Vitamins
Warfarin
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions

Antifibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Hemostatics
Coagulants
Hematologic Agents
Therapeutic Uses
Anticoagulants

ClinicalTrials.gov processed this record on May 24, 2012