Factor VII, Prothrombin Complex Concentrate, and Fresh Frozen Plasma in Warfarin-Related Intracranial Hemorrhage

NCT00770718 | Terminated Phase 1 DMC

• 1 other identifier: 21152
• Study Type: interventional
• Target: 2
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this dose-ranging pilot study is to compare Recombinant Activated Factor VII, Prothrombin Complex Concentrate and Fresh Frozen Plasma (each starting at low doses with escalation if necessary) for the reversal of warfarin in the setting of acute intracranial hemorrhage.

Conditions

Intracranial Hemorrhage

Keywords

intracranial hemorrhage; warfarin; anticoagulant; Factor VII; Prothrombin

Outcome Measures

Primary Outcomes (1)

• Normalization of INR (<1.4)

  20min, 2hrs, 4hrs, 6hrs, 24hrs

Secondary Outcomes (5)

• Hematoma progression

  24hrs

• Neurological status

  24hrs & 1month

• Timing of intervention completion

  24hrs

• Dosing of intervention required

  24hrs

• Medical complications during hospitalization

  days

Study Arms (3)

Recombinant Activated Factor VII

EXPERIMENTAL

The first five patients who meet the selection criteria will be administered an intravenous dose of rFVIIa 1mg upon arrival. INR will be drawn at 20 minutes post-rFVIIa administration. If normalized (≤1.3), then repeat INR with be drawn every 2 hours thereafter for 6 hours total, and again at 24 hours after initial administration. If at any time, the INR is \>1.3, then rFVIIa 1mg will be readministered and the INR will again be checked 20 minutes after administration and every 2 hours for 6 hours total and again at 24 hours post-administration. This may be repeated until a total dose of 80mcg/kg has been given. If a maximum total of 80mcg/kg has been administered without successful correction of INR, then FFP infusions will be utilized to complete correction.

Drug: Recombinant Activated Factor VII (rFVIIa)

Prothrombin Complex Concentrate (PCC)

EXPERIMENTAL

5 patients will receive PCC based on ideal body weight. Each patient will receive 30 i.u./kg ideal body weight as is rounded to the nearest dispensed vial size. Vials are dispensed as 5mL (500 i.u.), 10mL (1000 i.u.), or 10mL (1500i.u.). INR will be drawn at 20 minutes post-administration and, if normalized (≤1.3), 2 hours post-administration and every 2 hours for 6 hours total. The INR will also be checked 24 hours post-administration. If at any time, the INR is \>1.3, then PCC will be readministered at the same dose and the INR will again be checked 20 minutes after administration and every 2 hours for 6 hours total and again at 24 hours post-administration. A maximum total of 60 iu/kg can be administered before FFP will be used to complete the correction.

Drug: Prothrombin Complex Concentrate

Fresh Frozen Plasma (FFP)

ACTIVE COMPARATOR

The last five patients will receive transfusions of FFP to normalize INR. If the initial INR is between 2-4, then 2 units of FFP (Round 1) will be administered emergently. If the initial INR is \>4, then 4 units of FFP will be administered (Round 1). The INR will be checked after each round of FFP infusion completed. Once INR ≤1.3, then the INR will be again checked every 2 hours after normalization for 6 hours total and then 24 hours post-initial infusion. If the INR should ever return to \>1.3, then repeat infusions of FFP will begin as outlined above and the INR will be checked serially as defined above.

Biological: Fresh Frozen Plasma

Interventions

Recombinant Activated Factor VII (rFVIIa) DRUG

Five patients who meet the selection criteria will be administered an intravenous dose of rFVIIa 1mg upon arrival. INR will be drawn at 20 minutes post-rFVIIa administration. If normalized (≤1.3), then repeat INR with be drawn every 2 hours thereafter for 6 hours total, and again at 24 hours after initial administration. If at any time, the INR is \>1.3, then rFVIIa 1mg will be readministered and the INR will again be checked 20 minutes after administration and every 2 hours for 6 hours total and again at 24 hours post-administration. This may be repeated until a total dose of 80mcg/kg has been given.

Also known as: Novoseven®

Recombinant Activated Factor VII

Prothrombin Complex Concentrate DRUG

5 patients will receive PCC based on ideal body weight. Each patient will receive 30 i.u./kg ideal body weight as is rounded to the nearest dispensed vial size. Vials are dispensed as 5mL (500 i.u.), 10mL (1000 i.u.), or 10mL (1500i.u.). INR will be drawn at 20 minutes post-administration and, if normalized (≤1.3), 2 hours post-administration and every 2 hours for 6 hours total. The INR will also be checked 24 hours post-administration. If at any time, the INR is \>1.3, then PCC will be readministered at the same dose and the INR will again be checked 20 minutes after administration and every 2 hours for 6 hours total and again at 24 hours post-administration. A maximum total of 60 iu/kg can be administered.

Also known as: Profilnine®

Prothrombin Complex Concentrate (PCC)

Fresh Frozen Plasma BIOLOGICAL

Five patients will receive transfusions of FFP to normalize INR. If the initial INR is between 2-4, then 2 units of FFP (Round 1) will be administered emergently. If the initial INR is \>4, then 4 units of FFP will be administered (Round 1). The INR will be checked after each round of FFP infusion completed. Once INR ≤1.3, then the INR will be again checked every 2 hours after normalization for 6 hours total and then 24 hours post-initial infusion. If the INR should ever return to \>1.3, then repeat infusions of FFP will begin as outlined above and the INR will be checked serially as defined above.

Also known as: FFP

Fresh Frozen Plasma (FFP)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Non-traumatic intracranial hemorrhage (subdural or intraparenchymal)
• Known warfarin ingestion
• INR ≥2.0
• GCS \<13

You may not qualify if:

• Pregnancy
• History of venous thrombosis or pulmonary embolus
• Acute myocardial infarction
• Acute stroke

Sponsors & Collaborators

• University of Utah: lead
• Sheila B. Terry Memorial Research Fund: collaborator

MeSH Terms

Conditions

Intracranial Hemorrhages

Interventions

recombinant FVIIa; Factor IX; Profilnine SD

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Enzyme Precursors; Enzymes and Coenzymes; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Protein Precursors; Biological Factors

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: October 9, 2008
• First Posted: October 10, 2008
• Study Start: April 1, 2008
• Primary Completion: April 1, 2010
• Study Completion: April 1, 2010
• Last Updated: November 24, 2011

Record last verified: 2011-11