Safety and Efficacy of Activated Recombinant Human Factor VII in Haemophilia Patients With Inhibitors During and After Major Surgery

Study Overview
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Brief Summary
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This trial is conducted in North America. The aim of this trial is to compare the safety and efficacy of activated recombinant human factor VII in patients with haemophilia A or B undergoing major surgical procedures.

Official Title
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An Open-Label, Randomized, Parallel, Multicenter Trial Comparing the Safety and Efficacy of rFVIIa When Administered as i.v. Bolus or i.v. Continuous Infusion to Hemophiliacs With Inhibitors During and After Major Surgery

Conditions
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Congenital Bleeding Disorder, Haemophilia A With Inhibitors, Haemophilia B With Inhibitors

Intervention / Treatment
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* Drug: activated recombinant human factor VII
* Drug: activated recombinant human factor VII
* Other: factor IX
* Drug: factor VIII


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have haemophilia A or B with inhibitors to factor VIII or IX, respectively Have had a historical inhibitor level of at least five Bethesda units or have had an inadequate haemostatic response to 250 U/kg of factor VIII or IX or have had an inadequate response to FEIBA Require pre-planned major surgery in hospital Exclusion Criteria: Have participated in or have been treated with any investigational drug other than activated recombinant human factor VII within the last thirty days Have been treated with any haemostatic agent, including rFVIIa, within 48 hours of preoperative dose Have any haemostatic disorder other than haemophilia

Ages Eligible for Study
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Minimum Age: 5 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Continuous infusion<br> | Drug: activated recombinant human factor VII<br>* Infused continuously at 50 mcg/kg/hr through Day 5 then at 25 mcg/kg/hr on Days 6 to10.<br>|
| Experimental: Bolus injection<br> | Drug: activated recombinant human factor VII<br>* Injected every 2 hours during surgery through Day 5, then every 4 hours for Days 6 to 10.<br>|
| Experimental: Control<br> | Other: factor IX<br>* Patients with haemophilia A or B without inhibitors undergoing similar surgery were treated in accordance with local standard of care per physician's orders.<br>Drug: factor VIII<br>* Patients with haemophilia A or B without inhibitors undergoing similar surgery were treated in accordance with local standard of care per physician's orders.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Presence and maintenance of haemostasis |  |  | 
| Changes in FVII:C (Factor VII clotting activity) levels following administration of activated recombinant human factor VII |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events |  |  | 
| Changes in coagulation-related parameters |  |  |