Plain English Summary
Background and study aims
Newborn babies and infants needing surgery for congenital heart disease suffer the most from bleeding within the chest. As a result, they are frequently exposed to many blood products, and may also suffer consequences of blood loss. We want to find out whether giving a new blood product, human fibrinogen concentrate, to these infants, will reduce bleeding and exposure to other blood products. A unique aspect of this study will be that study drug exposure and dose will be personalised to the patient on the basis of bleeding risk. Because bleeding risk cannot be estimated accurately before the operation, we will assess this during the operation using a test for coagulation, known as rotational thromboelastometry (ROTEM).
Who can participate?
Babies who are aged less than 36 weeks with congenital heart disease requiring surgery.
What does the study involve?
We will give the study drug to only those infants who are at higher risk of bleeding during the ROTEM screening during the operation. These infants will be randomly allocated to receive either fibrinogen or a placebo (dummy). Infants at lower risk will not be allocated to any group, but remain in the study, forming an observational group. All infants will receive standard care with respect to all other aspects.
What are the possible benefits and risks of participating?
As this is an early phase trial, it is impossible to delineate risks or benefits in any meaningful way.
Where is the study run from?
Evelina Childrens Hospital (UK)
When is the study starting and how long is it expected to run for?
The study starts in June 2014 and ends in March 2016
Who is funding the study?
CSL Behring (UK)
Who is the main contact?
Dr Shane Tibby
Shane.Tibby@gstt.nhs.uk
Trial website
Contact information
Type
Scientific
Primary contact
Dr Shane Tibby
ORCID ID
Contact details
2nd floor
Evelina Childrens Hospital
Westminster Bridge Road
London
SE1 7EH
United Kingdom
-
Shane.Tibby@gstt.nhs.uk
Additional identifiers
EudraCT number
2013-003532-68
ClinicalTrials.gov number
Protocol/serial number
16254
Study information
Scientific title
Fibrinogen concentrate supplementation in the management of bleeding during paediatric cardiopulmonary bypass: a phase 1B/2A, open-label dose-escalation study
Acronym
Study hypothesis
Fibrinogen concentrate supplementation during paediatric cardiopulmonary bypass may decrease the incidence and severity of postoperative bleeding, and reduce the need for transfusion of blood and ancillary blood products (platelets, fresh frozen plasma, and cryoprecipitate). The primary objective of this trial is to determine the dose of intraoperative fibrinogen concentrate required to achieve physiological levels of fibrin polymerization of 8 to 13 mm as measured by the rotational thromboelastometry (ROTEM) measure of fibrin-based clotting: FibTEM MCF (equating to plasma fibrinogen concentrations of 1.5 to 2.5 g/L), immediately prior to separation from cardiopulmonary bypass in neonates and children < 12 kg.
Ethics approval
London - London Bridge Research Ethics Committee, 26/02/2014, ref: 14/LO/0267
Study design
Randomised; Interventional and Observational; Design type: Process of Care, Treatment, Cohort study
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Other
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Condition
Topic: Children; Subtopic: All Diagnoses; Disease: All Diseases
Intervention
Fibrinogen concentrate: IMP will be administered while on cardiopulmonary bypass. Patients will be screened while on cardiopulmonary bypass (approx 1 hour before end of operation) using Rotational Thromboelastometry: FibTEM MCF. If MCF<7mm, patients will be randomised to IMP:placebo 2:1. Dose will be tailored to patient based upon measured FibTEM MCF and desired target range.; Study Entry : Registration and One or More Randomisations
Intervention type
Drug
Phase
Phase II
Drug names
Fibrinogen concentrate
Primary outcome measure
1. Fibrinogen concentration (measured using the Clauss method)
2. Fibrin polymerization (measured by rotational thromboelastometry Fib-TEM MCF) achieved within 5 minutes of completion of study drug
Secondary outcome measures
1. Efficacy
1.1. Mediastinal drain losses in first 24 hours after PICU admission
1.2. Requirement for delayed sternal closure due to clinical bleeding/tamponade
1.3. Requirement for ancillary blood transfusions in first 24 hours post PICU admission
1.4. Use of intra- and post-operative ancillary clotting products
1.5. Fibrinogen levels and ROTEM variables at time points T4 T6
2. Safety
1.1. Incidence of major thrombotic event/thromboembolic associated complications
1.2. Allergic/hypersensitivity reaction to study drug
Overall trial start date
01/06/2014
Overall trial end date
02/03/2016
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Congenital heart disease requiring non-emergency* surgery on cardiopulmonary bypass
2. Age range: >36 weeks corrected gestation
3. Weight 2.5 to 12 kg
4. Informed consent to participate
*Non-emergency is defined as surgery that can be delayed >24 hours following diagnosis of congenital heart disease
Participant type
Patient
Age group
Child
Gender
Both
Target number of participants
Planned Sample Size: 90; UK Sample Size: 90
Participant exclusion criteria
1. Known pre-existing inherited coagulopathy
2. Known pre-existing inherited thrombophilia
3. Recent, acute (within previous 2 weeks) thrombosis in a major vessel or thrombotic related major complications (as defined in protocol sections 2.43 and 7.3)
4. Administration of antiplatelet agents (e.g. aspirin) <48 hours prior to surgery
5. Known hypersensitivity/allergy to the study drug or similar products
6. History of anaphylaxis
7. Enrolment in another clinical trial in the previous 3 months
8. Parent/guardian unable to provide informed consent (this can include insufficient understanding of the trial, as judged by the clinician taking consent)
9. Major comorbidity likely to increase risk of mortality from surgical procedure
10. Significant renal/liver impairment within 2 days of planned surgery (creatinine > 2x Upper Limit of Normal, Alanine Aminotransferase > 2x ULN)
Recruitment start date
01/06/2014
Recruitment end date
02/03/2016
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Evelina Childrens Hospital
London
SE1 7EH
United Kingdom
Funders
Funder type
Industry
Funder name
CSL Behring
Alternative name(s)
Funding Body Type
private sector organisation
Funding Body Subtype
corporate
Location
United States of America
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list