Vitamin K for Perioperative Warfarin Management

Vitamin K Reversal of INR for Perioperative Management of Warfarin: : A Pilot Study to Assess Feasibility

This is a feasibility study of uninterrupted warfarin with a one time dose of Vitamin K before a surgical procedure.

Study Overview

• Status: Recruiting
• Conditions: Anticoagulant Therapy
• Intervention / Treatment: Drug: Vitamin K; Drug: Warfarin (standard without loading); Drug: Warfarin (standard with loading)

Detailed Description

Historically, warfarin is held for 5 days before a surgical procedure to obtain a safe INR (international normalized ratio) that minimizes bleeding risk. However, there is a strong rationale for continuing warfarin uninterrupted in the perioperative space and giving a one-time vitamin K dose to get a safe INR pre-operatively. This feasibility study will recruit patients who use warfarin and will measure their INR response after receiving a single pre-procedure vitamin K dose. This study will also assess the use of a one-time "loading" dose immediately post-operative to help the INR return to the therapeutic range sooner than continuing with the standard warfarin dosing.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Geoffrey Barnes, MD; Phone Number: 734 936-4000; Email: gbarnes@med.umich.edu

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • Michigan Medicine
      • Contact: Geoffrey Barnes, MD; Phone Number: 734 936-4000; Email: gbarnes@med.umich.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Warfarin therapy for ≥3 months
• Use of home INR testing equipment
• Scheduled for a surgical procedure that requires INR ≤ 1.5 (typically achieved with warfarin interruption)
• INR ≤ 4 on day 7-10 prior to procedure

Exclusion Criteria:

• Surgical procedure does not require INR ≤1.5 (typically achieved with warfarin interruption)
• Surgical procedure with a high risk of bleeding or complications (urologic procedures, bronchoscopy, epidural injections, nerve blocks, spinal surgery)
• Warfarin therapy for < 3 months
• Lack of English language proficiency
• Use of a Heartmate II or HVAD left ventricular assist device
• Recent thrombotic event (within 3 months)
• CHA2DS2-VASc score >6
• INR >4 on day 7-10 prior to procedure
• Hypersensitivity to any component of Vitamin K or simple syrup (used in the compounding process)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Standard Warfarin Dosing with Vitamin K; Patients will receive their standard warfarin dosing before, during, and after their procedure. This is in addition to a one time dose of oral vitamin K pre-procedure.	Drug: Vitamin K; 10 mg of oral vitamin K will be given approximately 36-48 hours before procedure.; Drug: Warfarin (standard without loading); Patients receive their standard warfarin dosing without interruption.; Other Names: Coumadin
Experimental: Loading Warfarin Dosing with Vitamin K; Patients will receive their standard warfarin dosing before and during their procedure. On the night following the procedure, they will receive a one time loading dose of warfarin (twice their normal dose). Patients will then resume normal dosing of warfarin. This is in addition to a one time dose of oral vitamin K pre-procedure.	Drug: Vitamin K; 10 mg of oral vitamin K will be given approximately 36-48 hours before procedure.; Drug: Warfarin (standard with loading); Patients receive their standard warfarin dosing without interruption; patients also receive a one time loading dose (twice normal dose) of warfarin on the evening following their procedure.; Other Names: Coumadin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of patient recruitment	Percentage of recruited patients among those initially screened	Within two weeks (from outreach to five days prior to procedure)
INR reversal	Percentage of enrolled patients with an INR less than or equal to 1.5 on morning of procedure	Within 12 hours prior to procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fidelity to intervention protocol	Percent of patients who achieved both elements of the intervention: 1) continued warfarin uninterrupted peri-operatively; 2) Administration of oral vitamin K on the evening of pre-operative day 2	12 day span from 2 days pre-operative through 10 days post-operative
Fidelity to randomization	Percent of patients who used the appropriate dose of warfarin that was recommended immediately post -procedure based on randomization	24 hours (day of procedure)
Cost per recruited patient	Study costs per patient recruited through end of follow up. Inclusive of personnel, supplied, medication costs.	12 day span from 2 days pre-operative through 10 days post-operative
Patient acceptability	Data gathered with an acceptability survey, measured on a Likert scale ranging from 1-5 where 5 means most acceptable and 1 means least acceptable.	10 days post procedure
Clinical acceptability	Data gathered with an acceptability survey, on a Likert scale ranging from 1-5 where 5 means most acceptable and 1 means least acceptable.	10 days post procedure
Therapeutic INR by post-operative day 5	Percent of patients whose INR has returned to their therapeutic range by day 5 post-procedure	day 5 post procedure
Adverse events	Any bleeding or thromboembolic complication that occurs with 30-days following the surgical procedure	30 days post procedure
Canceled procedures	Percent of procedures that are canceled due to an INR greater than 1.5	24 hours prior to procedure
Additional warfarin reversal pre-operative	Use of any additional warfarin reversal agents (e.g., fresh frozen plasma, prothrombin complex concentrate, additional vitamin K)	24 hours pre-procedure

Collaborators and Investigators

• Sponsor: University of Michigan
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Geoffrey Barnes, MD, University of Michigan

Study record dates

Study Major Dates

• Study Start (Actual): July 3, 2025
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: March 31, 2026
• First Submitted That Met QC Criteria: March 31, 2026
• First Posted (Actual): April 7, 2026

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 6, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pyrans; Hydrocarbons; Hydrocarbons, Cyclic; Terpenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Diterpenes; Coumarins; Benzopyrans; Naphthoquinones; Phytol; 4-Hydroxycoumarins; Vitamin K; Warfarin
• Other Study ID Numbers: HUM00264031; K24HL179410 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No