Efficacy and Safety Study of Octafibrin for On-demand Treatment of Acute Bleeding and to Prevent Bleeding During and After Surgery
|ClinicalTrials.gov Identifier: NCT02267226|
Recruitment Status : Completed
First Posted : October 17, 2014
Last Update Posted : June 7, 2018
|Condition or disease||Intervention/treatment||Phase|
|Congenital Fibrinogen Deficiency||Drug: Octafibrin||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||25 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Prospective, Open-label, Uncontrolled, Phase III Study to Assess the Efficacy and Safety of Octafibrin for On-demand Treatment of Acute Bleeding and to Prevent Bleeding During and After Surgery in Subjects With Congenital Fibrinogen Deficiency|
|Study Start Date :||September 2014|
|Actual Primary Completion Date :||January 23, 2018|
|Actual Study Completion Date :||January 23, 2018|
- Overall clinical assessment of the haemostatic efficacy of Octafibrin in treating the first documented bleeding episode of each patient [ Time Frame: 24 hours after last infusion for each bleeding episode ]
The first bleeding episode covers the time period from the first Octafibrin infusion until 24 hours (i.e., 1 day) after the last infusion.
The investigator's overall clinical assessment of haemostatic efficacy for bleeding will be based on a 4 point haemostatic efficacy scale. The final efficacy assessment of each patient will be adjudicated by the Independent Data Monitoring & Endpoint Adjudication Committee (IDMEAC). The number of subjects per outcome category will be assessed in the final analysis.
- Maximum clot firmness (MCF) assessment of each documented bleeding episode [ Time Frame: Before first infusion and 1 hour after end of first and last infusion of each documented bleeding episode ]MCF will be determined using thromboelastography (TEG) and will be used as a surrogate marker for haemostatic efficacy. TEG is a method for the continuous measurement of clot formation and clot firmness. It utilises a mechanical detection system which is based on the ability of the blood or plasma clot to form a mechanical coupling over a distance of 1 mm.
- Assessment of fibrinogen plasma level [ Time Frame: Before and 1 hour after the end of each subsequent infusion as well as at the time of the overall clinical assessment of haemostatic efficacy (i.e., 24 hours after the last infusion of each documented bleeding episode) ]Fibrinogen plasma level will be assessed using the Clauss fibrinogen assay.
- Response as indicated by incremental in vivo recovery (IVR), calculated as the maximum increase in plasma fibrinogen between pre- and post-infusion [ Time Frame: Pre-infusion and 1 and 3 hours post-infusion ]
IVR will be determined using the following approaches:
- Incremental IVR (response): calculated as the maximum increase in plasma fibrinogen (i.e., Clauss data) between pre-infusion and 1 and 3 hours post-infusion, divided by the exact dose of Octafibrin.
- Classical IVR: calculated as the maximum increase in plasma fibrinogen (i.e., Clauss data) between pre-infusion and 1 and 3 hours post-infusion, divided by the total dose of Octafibrin per expected plasma volume.
- Efficacy of Octafibrin in all bleeding episodes collected in the study [ Time Frame: 24 hours after last infusion for each bleeding episode ]The investigator's overall clinical assessment of haemostatic efficacy for bleeding will be based on a 4 point haemostatic efficacy scale. The final efficacy assessment of each patient will be adjudicated by the Independent Data Monitoring & Endpoint Adjudication Committee (IDMEAC).
- Efficacy of Octafibrin in preventing bleeding during and after surgery [ Time Frame: First dose of Octafibrin administered prior to elective surgery to at least 3 post-operative days for minor and 7 post-operative days for major surgeries or last post-operative infusion, whichever comes last ]The efficacy of Octafibrin will be assessed at the end of surgery by the surgeon and post-operatively by the haematologist using two 4-point haemostatic efficacy scales. An overall efficacy assessment taking both the intra- and post-operative assessment into account will be adjudicated by the IDMEAC.
- Analysis of safety: Adverse events [ Time Frame: Start of the first Octafibrin infusion until the end of each 30-day observation and follow-up period for on-demand treatment or until the Last Post-Operative Day in surgeries ]Adverse events, including thromboembolic complications and early signs of allergic or hypersensitivity reactions.
- Analysis of safety: Immunogenicity testing for anti-fibrinogen antibodies [ Time Frame: Start of the first Octafibrin infusion until the end of each 30-day observation and follow-up period for on-demand treatment or until the Last Post-Operative Day in surgeries ]Immunogenicity testing for the presence of anti-fibrinogen antibodies at Day 14 and Day 30 after the administration of Octafibrin for bleeding.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02267226
|United States, Florida|
|Miami Children's Hospital|
|Miami, Florida, United States, 33155|
|Dept of Clinical Hematology for Hemorrhagic Diatheses and Anaemia, SHAT "Joan Pavel"|
|St. John's Medical College Hospital|
|Dept of Hematology, Christian Medical College|
|Iran, Islamic Republic of|
|Seyed Al Shohada Hospital|
|Isfahan, Iran, Islamic Republic of|
|Shīrāz, Iran, Islamic Republic of|
|Hotel-Dieu de France|
|Haematological Scientific Center of Ministry of Healthcare of the Russian Federation|
|Moscow, Russian Federation|
|Centre of Excellence in Thrombosis & Hemostasis, King Saud University|
|Riyadh, Saudi Arabia|
|Dept of Haematology, Ege University Children's Hospital|
|Centre for Haemostasis & Thrombosis, St Thomas' Hospital|
|London, United Kingdom|
|Study Director:||Cristina Solomon, MD||Octapharma|