Condition category
Surgery
Date applied
01/05/2014
Date assigned
01/05/2014
Last edited
09/07/2014
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

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 Children’s 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 Children’s 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

14/LO/0267; First MREC approval date 26/02/2014

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 below 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 measures

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

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

2nd floor, Evelina Children’s Hospital
London
SE1 7EH
United Kingdom

Sponsor information

Organisation

Guy's and St Thomas' NHS Foundation trust (UK)

Sponsor details

King’s Health Partners Clinical Trials Office
16th Floor
Tower Wing
Guy's Hospital
Great Maze Pond
London
SE1 9RT
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Industry

Funder name

CSL Behring (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

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

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes