Clinical trial NCT01086852: Safety & Efficacy of BPL's High Purity FACTOR X in Treatment of Factor X Deficient Subjects Undergoing Surgery
Official title: A Phase III Open, Multicentre Study to Investigate the Safety and Efficacy of BPL's High Purity FACTOR X in the Treatment of Factor X Deficient Subjects Undergoing Surgery
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Factor X Deficiency
Keywords: Factor X deficiency
surgery
Factor X deficiency subjects requiring surgery
Lead sponsor: Bio Products Laboratory
Sponsor class: OTHER
First posted: 2010-03-15
Enrollment: 4
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To primary efficacy variable is to assess the presence or absence of excessive blood loss during and after surgery.

The secondary efficacy endpoints are as follows:

1. A subjective overall assessment by the investigator of FACTOR X in the control of bleeding during surgery.
2. The incidence of bleeding episodes during treatment with FACTOR X while the subject is at risk of post-operative bleeding, including location and duration.
3. Incremental recovery of FX:C and FX:Ag after the pre-surgery bolus infusion.
4. Assessment of FX:C and FX:Ag levels on each day post-surgery.
5. Assessment of the cumulative weight-adjusted doses of FACTOR X as measured by FX:C (IU/kg body weight) administered to each subject to maintain haemostasis.
6. Assessment of the cumulative doses of FACTOR X as measured by FX:C (IU) administered to each subject to maintain haemostasis.
7. Amount of weight-adjusted FACTOR X as measured by FX:C (IU/kg body weight) administered daily (day of surgery and each post-operative day) to maintain haemostasis.

Detailed description: To investigate the safety and efficacy of FACTOR X administered by bolus infusion to prevent bleeding and achieve haemostasis in factor X deficient subjects undergoing surgery.

Eligibility criteria: Inclusion Criteria:

* Subjects who are at least 12 years of age at date of written informed consent/assent.
* Subjects who have given written informed consent or, for subjects aged 12-17 years (inclusive), have given written assent and whose parent/guardian has given written informed consent.
* Subjects with hereditary mild to severe Factor X deficiency (\<20% basal FX activity), including previously untreated subjects OR those currently treated with Fresh Frozen Plasma (FFP), Prothrombin Complex Concentrate (PCC) or factor IX/X concentrate by prophylaxis or on demand.
* Subjects who are to undergo surgery in which the investigator believes a factor X concentrate will be required due to a prior history of unusual bleeding either spontaneously or after surgery or trauma in the absence of treatment with a factor X containing product.
* Pregnant subjects undergoing obstetric delivery (including Caesarean surgery and vaginal delivery) may enter the study. Female subjects of child-bearing potential must have a negative result on a human chorionic gonadotropin-based pregnancy test. If a female subject is or becomes sexually active, she must practice contraception by using a method of proven reliability for the duration of the study.

Exclusion Criteria:

* Subjects who are required or expected to take other factor X containing medications during or after surgery.
* Subjects with a history of inhibitor development to FX or a detectable inhibitor to FX (≥0.6 BU) on the Nijmegen-Bethesda assay at screening. Obtaining a FX inhibitor result at screening is not mandatory if the subject is to undergo emergency surgery and the local laboratory is unable to perform the analyses prior to the surgical procedure.
* Subjects with thrombocytopenia (platelets \< 50 x 109/L).
* Subjects who have clinically significant renal disease (creatinine \>200µmol/L).
* Subjects who have clinically significant liver disease (ALT levels greater than three times the upper limit of normal).
* Subjects known to have other coagulopathy or thrombophilia.
* Subjects who are currently participating or have participated in another trial within the last 30 days, with the exception of the BPL Factor X PK study (protocol number Ten01).
* Female subjects who are lactating.
* Subjects who have known or suspected hypersensitivity to the investigational medicinal product or its excipients.
* Subjects known to have abused chemicals or drugs within the past 12 months.
* Subjects with a history of unreliability or non-cooperation.

Primary outcomes:
measure: Clinical Estimation of Volume of Blood Loss During Surgery
timeFrame: Blood loss is measured during and after surgery, the overall assessment is made after the last dose of FACTOR X.
measure: Clinical Assessment of Blood Loss During Surgery Against the Volume of Blood Loss Expected in Patients Without a Bleeding Disorder.
timeFrame: After wound closure
measure: Requirement for Blood Transfusion
timeFrame: during and after surgery
measure: Number of Post Operative Bleeding Episodes (See Table Below)
timeFrame: End of surgery till end of study
measure: Change of Haemoglobin From Pre-surgery Till End of Treatment
timeFrame: 2 hrs pre-operatively till end of treatment
measure: Number of Participants With Degree of Bleeding Control Rated as Excellent.
timeFrame: During and till end of treatment
Secondary outcomes:
measure: Incremental Recovery After Bolus Dose of FACTOR X
timeFrame: incremental recovery was assessed at approximately 30 minutes after the pre surgery bolus
measure: Dose Per Infusion (IU/kg)
timeFrame: before surgery, during the post operative period
Other outcomes:
Locations:
city: Houston
country: United States
facility: University Of Texas Health Science Center, Gulf States Hemophilia and Thrombophilia Center 6655 Travis St
state: Texas
city: Madrid
country: Spain
facility: Unidad Coagulopatías, Congenitas, Edificio Dotacional, 1ra Planta Hospital Universito La Paz
city: Bornova
country: Turkey
facility: Ege University School of Medicine, Departmant of Pediatric Hematology
state: Izmir
city: Istanbul
country: Turkey
facility: Istanbul University Cerrahpasa Medicine Faculty Department of Pediatric Hematology
city: Truro
country: United Kingdom
facility: Department of Hematology, Royal Cornwall Hospital,
state: Cornwall
city: Hampstead
country: United Kingdom
facility: The Katherine Dormandy Haemophilia Centre and Thrombosis Unit, The Royal Free Hospital,Pond Street
state: London
city: London
country: United Kingdom
facility: Hammersmith Hospital
Study officials:
affiliation: Bio Products Laboratory
name: Tim Aldwinckle
role: PRINCIPAL_INVESTIGATOR
References: