Fixed Versus Variable Dosing of 4-factor Prothrombin Complex Concentrate for Emergent Warfarin Reversal

NCT03064035 | Completed Phase 4 Results FDA Drug

• 1 other identifier: A16-732
• Study Type: interventional
• Target: 79
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study is to determine if a fixed dose of 4-factor prothrombin complex concentrate (4FPCC) is as effective as the current standard of care. 4FPCC is used to reverse the effects of warfarin when a patient has emergent bleeding. The investigators hope that this study will help doctors treat patients quicker in the future. In addition, it may be cheaper for patients and hospitals. This is the same medication the doctor would use to reverse warfarin's effects, but at a lower dose. Hypothesis: A fixed dose of 4FPCC will be comparable to FDA-approved variable dosing for reversal of warfarin-induced anticoagulation (defined as an international normalized ratio \[INR\] ≤ 1.5) in patients with an INR ≥2 experiencing an emergent bleed or requiring emergent surgery.

Conditions

Acute Bleeding on Long-Term Anticoagulation Therapy; Hemorrhage; Significant Bleeding in Patients With a Coagulopathy (Prolonged Thrombin Time); Urgent Reversal of Vitamin K Antagonist (VKA) Anticoagulation

Outcome Measures

Primary Outcomes (1)

• Number of Participants Who Demonstrated Significant Reversal of INR Within 15 Minutes

  To evaluate whether fixed dose 4FPCC is acceptably comparable to variable dosing with respect to anticoagulation reversal, as defined by a targeted INR of ≤1.5

  15 minutes

Secondary Outcomes (2)

• Number of Participants With a Thromboembolic Event

  up to 7 days post administration of 4FPCC

• Total Cost of Dosing Strategy

  Hospital Stay, Up to 6 months

Study Arms (2)

Fixed dose 4FPCC

EXPERIMENTAL

Incorporating a fixed dose of 1500 IU. If the patient receiving the 1500 IU fixed dose remains in a bleeding state and the INR remains above goal, an additional 500 IU may be administered at the physician's discretion to minimize bleeding and attempt to achieve hemostasis.

Drug: 4-factor prothrombin complex concentrate (4FPCC)

Variable dose 4FPCC

ACTIVE COMPARATOR

The FDA-approved variable dosing algorithm is as follows: initial INR 2-3.9: 25 IU/kg (maximum dose 2500 IU), initial INR 4-6: 35 IU/kg (maximum dose 3500 IU), and initial INR \>6: 50 IU/kg (maximum dose 5000 IU). The patient weight will be obtained using a scale and documented by the treating registered nurse

Drug: 4-factor prothrombin complex concentrate (4FPCC)

Interventions

4-factor prothrombin complex concentrate (4FPCC) DRUG

4-factor prothrombin complex concentrate (4FPCC) contains all of the vitamin K-dependent clotting factors inhibited by warfarin, making it desirable for use in warfarin reversal for emergent bleeds. Multiple guidelines currently recommend 4FPCC for warfarin reversal in vitamin K-dependent major bleeding or intracranial hemorrhage. 4FPCC has a fast onset of action and has demonstrated significant reversal of INR within 10 minutes. Its duration of action is up to 8 hours, and for this reason it should be given concurrently with vitamin K. Vitamin K has a delayed onset of action due to its need to stimulate the synthesis of clotting factors so its effects begin as the effects of 4FPCC diminish. 4FPCC is the standard of care treatment for this clinical population in the Regions Hospital Emergency Department.

Fixed dose 4FPCC; Variable dose 4FPCC

Eligibility Criteria

• Age: 18 Years - 125 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Chronic anticoagulation with warfarin and initial INR ≥2
• Emergent bleeding (i.e. intracranial hemorrhage, gastrointestinal hemorrhage, urgent invasive procedures, etc.) or urgent surgery requiring reversal of INR to ≤1.5

You may not qualify if:

• Younger than 18 years of age
• History of heparin-induced thrombocytopenia (HIT)
• Patients without initial or post-administration INR readings
• Patients with an initial INR \<2
• Pregnant patients
• Prisoners

Sponsors & Collaborators

• HealthPartners Institute: lead

Study Sites (1)

Regions Hospital

Saint Paul, Minnesota, 55101, United States

Location

MeSH Terms

Conditions

Hemorrhage

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Zachary Stoecker, PharmD
• Organization: Methodist Hospital

Zachary.Stoecker@parknicollet.com

952-977-5520

Study Officials

• Zachary Stoecker, PharmD

  Regions Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: For adults on long-term warfarin therapy who present to the ED with emergent bleeding, or who are in need of urgent invasive surgical procedures: the exposure of interest will be fixed vs. variable dose 4FPCC, to which eligible patients will be randomly assigned in a 1:1 ratio.

Study Record Dates

• First Submitted: February 16, 2017
• First Posted: February 24, 2017
• Study Start: April 5, 2017
• Primary Completion: April 17, 2019
• Study Completion: April 24, 2019
• Last Updated: September 14, 2023
• Results First Posted: July 11, 2023

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)