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 III

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

Drug Information available for: Vitamin K1 Vitamin K Warfarin Phytonadione Warfarin sodium Warfarin potassium

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
Estimated Study Completion Date:	April 2010
Estimated Primary Completion Date:	November 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Vitamin K: Active Comparator	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: Placebo Comparator	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

Contacts

Contact: Habeeb Majeed, BSc, MSc(c)	613-798-5555 ext 13805	hmajeed@ohri.ca
Contact: Nicholas Galambos, MBA	613-798-5555 ext 19767	ngalambos@ohri.ca

Locations

Canada, Ontario
Ottawa Hospital Thrombosis Clinic	Recruiting
Ottawa, Ontario, Canada, K1Y4E9
Contact: Philip S Wells, MD, MSc 613-737-8851 pwells@ohri.ca
Contact: Nicholas Galambos, MBA 613-798-5555 ext 19767 ngalambos@ohri.ca
Principal Investigator: Philip S Wells, MD, MSc
Sub-Investigator: Habeeb Majeed, BSc, MSc(c)
Sub-Investigator: Marc Rodger, MD, MSc

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:	Ottawa Health Research Institute (OHRI) ( Dr. Philip S Wells (Chair, Department of Medicine) )
Study ID Numbers:	OHREB #2008555-01H
Study First Received:	November 18, 2008
Last Updated:	July 8, 2009
ClinicalTrials.gov Identifier:	NCT00794755 History of Changes
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:

Anticoagulants
Molecular Mechanisms of Pharmacological Action
Coagulants
Growth Substances
Hematologic Agents
Physiological Effects of Drugs
Warfarin
Vitamin K 1

Pharmacologic Actions
Hemostatics
Fibrin Modulating Agents
Antifibrinolytic Agents
Therapeutic Uses
Vitamins
Vitamin K
Micronutrients

ClinicalTrials.gov processed this record on February 08, 2010