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
Trial Snapshot
- Phase
- Phase 3
- Status
- Terminated
- Sponsor
- Enrollment
- 4
- Locations
- 14
- Primary Endpoint
- Number of Post Operative Bleeding Episodes (See Table Below)
Study Overview
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:
- A subjective overall assessment by the investigator of FACTOR X in the control of bleeding during surgery.
- The incidence of bleeding episodes during treatment with FACTOR X while the subject is at risk of post-operative bleeding, including location and duration.
- Incremental recovery of FX:C and FX:Ag after the pre-surgery bolus infusion.
- Assessment of FX:C and FX:Ag levels on each day post-surgery.
- 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.
- Assessment of the cumulative doses of FACTOR X as measured by FX:C (IU) administered to each subject to maintain haemostasis.
- 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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 12 Years to — (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Arms & Interventions
FACTOR X
Human Coagulation Factor X
Intervention: FACTOR X (Biological)
Outcomes
Primary Outcomes
Number of Post Operative Bleeding Episodes (See Table Below)
Time Frame: End of surgery till end of study
Bleeding was assessed at least once each day by the investigator, more frequently if indicated by the severity of the operation or the subject's response. This included all bleeding episodes from the end of the surgical procedure until the subject was no longer at risk of bleeding due to surgery
Clinical Assessment of Blood Loss During Surgery Against the Volume of Blood Loss Expected in Patients Without a Bleeding Disorder.
Time Frame: After wound closure
The investigator's estimation of the volume of blood loss during surgery compared to the volume of blood loss expected in patients without a bleeding disorder undergoing the same surgical procedure and reported as greater than, equal to or less than.
Change of Haemoglobin From Pre-surgery Till End of Treatment
Time Frame: 2 hrs pre-operatively till end of treatment
The subject's haemoglobin was measured pre operatively, within 2 hours post operatively and at the End of Treatment Assessment. Changes in the subject's haemoglobin from pre to post operatively and from post operatively to the End of Treatment Assessment were assessed, taking into account the volume of fluid infused into the subject during the intervening periods, any blood transfusions in the intervening periods, the subject's haematocrit at the same time points and the subject's pre dose serum ferritin
Clinical Estimation of Volume of Blood Loss During Surgery
Time Frame: Blood loss is measured during and after surgery, the overall assessment is made after the last dose of FACTOR X.
As soon as possible after wound closure, the investigator estimated the volume of blood loss during surgery and made a clinical assessment against the volume of blood loss typically expected in a normal patient (i.e. one without a bleeding disorder and undergoing the same surgical procedure). The assessment may have been supported by a swab and pad count. The clinical assessment was rated as follows: * Blood loss less than expected * Blood loss as expected * Blood loss more than expected * Blood loss excessive (defined as more than twice the pre defined amount that would be expected in a normal patient for this type of surgery)
Requirement for Blood Transfusion
Time Frame: during and after surgery
Number of blood transfusions required (units of packed red blood cells or units of whole blood) or infusion of autologous red cells during and after surgery
Number of Participants With Degree of Bleeding Control Rated as Excellent.
Time Frame: During and till end of treatment
Investigators made an overall assessment of FACTOR X in controlling bleeding at the End of Treatment Assessment. The degree of bleeding control was rated as excellent, good, poor or unassessable, in accordance with the following criteria listed below: * Excellent -Parameters were similar to those in subjects without a bleeding disorder. * Good -Parameters were inferior to those in subjects without a bleeding disorder, but no other factor X containing agents were required to restore haemostasis. * Poor - Blood loss was excessive (defined as more than twice the pre defined amount that would be expected in a subject without a bleeding disorder for this type of surgery) and/or Haemostasis was not achieved and/or Additional factor X containing agents were required to restore haemostasis. * Unassessable -Efficacy was not possible to assess, or Additional factor X containing agents (excluding blood transfusions) were required before efficacy of FACTOR X could be assessed.
Secondary Outcomes
- Dose Per Infusion (IU/kg)(before surgery, during the post operative period)
- Incremental Recovery After Bolus Dose of FACTOR X(incremental recovery was assessed at approximately 30 minutes after the pre surgery bolus)