Use of Phytonadione to Reduce International Normalized Ratio (INR) Variability in Patients on Long-term Warfarin Therapy

Condition(s) targeted: Coagulation Delay

Intervention: phytonadione (Dietary Supplement); none-control group (Drug)

Phase: N/A

Status: Recruiting

Sponsored by: James A. Haley Veterans Administration Hospital

Official(s) and/or principal investigator(s):
To-Nga Huynh, PharmD, Principal Investigator, Affiliation: James A. Haley VA Hospital

Background: Warfarin is used as an anti-coagulant in patients at risk of developing thrombosis. It has a narrow therapeutic index necessitating close monitoring of International Normalized Ratio (INR). According to a meta-analysis, patients were in therapeutic range only 63. 6% of the time. This increases the risk of bleeding or thrombosis. Various retrospective and prospective studies have looked at supplementation with phytonadione in these patients to reduce the variability of INR showing an improvement in variability. Most of these studies have only been done in a small number of patients already on warfarin therapy. This study will focus on patients newly starting warfarin therapy. Methods: This study is a prospective, randomized, controlled trial performed at James A. Haley Veterans' Hospital (JAHVA). Patients who meet criteria and sign informed consent will receive either phytonadione with warfarin or warfarin alone. Based on a power calculation for 80%, a total of 370 patients will be enrolled (185 participants in each arm). Participants will be randomized to either intervention or control. Intervention group participants will be prescribed their usual starting dose of warfarin along with 200 mcg phytonadione by mouth daily. Control group participants will be prescribed their usual starting dose of warfarin. Both groups will follow the usual standard of care. They will come in for a follow-up INR and warfarin dose titration at least once per week until therapeutic, and then as instructed up to every 6 weeks thereafter. Both groups will participate in anticoagulation clinic activities that constitute the current standard of care. Intervention will last for a total of 6 months for each participant once enrolled. Hypothesis: Participants in the intervention group being supplemented with 200mcg of phytonadione will spend more total time with a therapeutic INR than participants in the control group.

Official title: Use of Phytonadione to Reduce INR Variability in Patients on Long-term Warfarin Therapy

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: The primary outcome of this study is to determine the length of time in therapeutic INR range for patients given phytonadione and warfarin compared to warfarin alone

Secondary outcome: Secondary outcomes include the number of adverse events in the form of bleeding or thrombosis for both groups.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Be eighteen years of age and older

- Have a long-term indication for warfarin (will need to be on warfarin for 6 months or

longer)

- Be a new patient on warfarin therapy, or a patient previously on warfarin therapy who

has been taken off therapy for more than 2 weeks and needs to be titrated again

- Anticipate receiving medical care at the study site for the duration of the study

- Have transportation to and from the JAHVA

- Have read and signed the Informed Consent document after the study has been fully

explained and has had all questions answered Exclusion Criteria:

- Have liver or kidney failure

- Are on hemodialysis or peritoneal dialysis

- Are pregnant or planning to become pregnant

- Have Alzheimer's disease, cognitive impairment, or visual impairment

- Are not compliant with medications

- Are participating in another study

- Have scheduled surgery or are planning to undergo major surgery

- Cannot be reached by telephone

- Take over-the-counter vitamin K supplementation except multivitamins

James A. Haley VA Hospital, Tampa, Florida 33612, United States; Recruiting
To-Nga Huynh, PharmD., Phone: 813-972-2000, Ext: 5356, Email: To-NgaNgoc.Huynh@va.gov
Carla Leto, PharmD., Phone: 813-972-2000, Ext: 5822, Email: Carla.Leto1@va.gov
To-Nga Huynh, PharmD., Principal Investigator
Betty Prihar, MD, Principal Investigator

Starting date: September 2011
Last updated: December 27, 2011