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

NCT01474460 | Completed DMC

• 1 other identifier: Pro00000493
• Study Type: interventional
• Target: 370
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Coagulation Delay

Keywords

warfarin; phytonadione; INR

Outcome Measures

Primary Outcomes (1)

• 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

  6 months

Secondary Outcomes (1)

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

  6 months

Study Arms (2)

Control group

PLACEBO COMPARATOR

The control group only receiving warfarin therapy (individualized therapy, hence no specific form, dosage, frequency and duration is applicable here - i.e. 5mg daily everyday for 6 months may be applicable to one patient but not all researched patients).

Dietary Supplement: phytonadione

Phytonadione

EXPERIMENTAL

Patients receiving 200mcg of phytonadione.

Dietary Supplement: phytonadione

Interventions

phytonadione DIETARY_SUPPLEMENT

Phytonadione 200mcg PO daily for 6 months + normal dose of warfarin and standard of care treatment

Also known as: Vitamin K, Coumadin

Control group; Phytonadione

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• James A. Haley Veterans Administration Hospital: lead

Study Sites (1)

James A. Haley VA Hospital

Tampa, Florida, 33612, United States

Location

MeSH Terms

Interventions

Vitamin K 1; Vitamin K; Warfarin

Intervention Hierarchy (Ancestors)

Naphthoquinones; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Phytol; Diterpenes; Terpenes; Quinones; Polycyclic Compounds; 4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• To-Nga Huynh, PharmD

  James A. Haley VA Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Anticoagulation Clinical Pharmacist

Study Record Dates

• First Submitted: November 15, 2011
• First Posted: November 18, 2011
• Study Start: September 1, 2011
• Primary Completion: November 1, 2015
• Study Completion: November 1, 2015
• Last Updated: March 9, 2017

Record last verified: 2017-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)