Clinical trial NCT01474460: Use of Phytonadione to Reduce International Normalized Ratio (INR) Variability in Patients on Long-term Warfarin Therapy
Official title: Use of Phytonadione to Reduce INR Variability in Patients on Long-term Warfarin Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Coagulation Delay
Keywords: warfarin
phytonadione
INR
Lead sponsor: James A. Haley Veterans Administration Hospital
Sponsor class: FED
First posted: 2011-11-18
Enrollment: 370
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: See above.

Eligibility 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

Primary outcomes:
measure: 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
timeFrame: 6 months
Secondary outcomes:
measure: Secondary outcomes include the number of adverse events in the form of bleeding or thrombosis for both groups.
timeFrame: 6 months
Other outcomes:
Locations:
city: Tampa
country: United States
facility: James A. Haley VA Hospital
state: Florida
Study officials:
affiliation: James A. Haley VA Hospital
name: To-Nga Huynh, PharmD
role: PRINCIPAL_INVESTIGATOR
References: