Fibrinogen Concentrate as Initial Treatment for Postpartum Haemorrhage: A Randomised Clinically Controlled Trial

Postpartum Haemorrhage Clinical Trial

— FIB-PPH  

Official title:

Fibrinogen Concentrate as Initial Treatment for Postpartum Haemorrhage - A Randomised Clinically Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01359878
• Other study ID #: 2009-017736-41
• Secondary ID: 2009-017736-4110
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: May 20, 2011
• Last updated: September 19, 2013
• Start date: May 2011
• Est. completion date: July 2013

Study information

• Verified date: September 2013
• Source: Copenhagen University Hospital at Herlev
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Danish Dataprotection AgencyDenmark: Danish Medicines AgencyDenmark: The Danish National Committee on Biomedical Research EthicsDenmark: The Regional Committee on Biomedical Research Ethics
• Study type: Interventional

Clinical Trial Summary

Severe maternal bleeding is a serious complication of birth and causes 125.000 deaths worldwide each year. The investigators aim to investigate if early treatment with fibrinogen concentrate versus saline can reduce the incidence of blood transfusion in women with postpartum haemorrhage.

A low level of fibrinogen has been associated with increased blood loss and transfusion requirements in different clinical settings including obstetrical bleeding. Early up-front treatment with fibrinogen may reduce incidence of transfusion by securing optimal haemostatic capacity in women with postpartum haemorrhage.

The investigators plan to enrol 245 patients on four hospitals in the Capital Region of Denmark during a two year period.

As safety measure the investigators plan to use TEG®/Functional Fibrinogen/Rapid-TEG as haemostatic monitoring of all participants during the trial: Baseline test is taken at inclusion before administration of fibrinogen concentrate/placebo. Further tests are taken immediately after intervention, 4 hours and 24 hours after. Baseline test is blinded to the providers of treatment - the rest is clinically available.

Description:

Experimental design Design: We plan to conduct a randomised double-blinded clinically controlled trial: The participants are assigned to either 1) placebo (100 ml of isotonic saline) i.v. or 2) the intervention drug: 2 g of fibrinogen concentrate (Haemocomplettan, CSL Behring) i.v. We intend to use a fixed dose for all patients randomized to the intervention group without prior measurement of the fibrinogen level. This strategy is primarily based on the clinical urgency since the treatment is required to be administered as early as possible.

Materials and duration of study Patients will be included during a two year period at the four largest hospitals in the Capital Region: Rigshospitalet, Hvidovre, Hillerød and Herlev if they fulfil the following eligibility criteria Plan of trial execution In order to secure the ethical aspect "Time for reflection" we will provide all pregnant women who appear in the centres during the trial period with written information on the trial during their midwife evaluation. Only 1,75% of these women are estimated to meet the inclusion criteria postpartum.

Intensive haemostatic monitoring Haemostatic blood samples including thrombelastography (TEG®), functional fibrinogen-assay for TEG®, Rapid-TEG, fibrinogen-level, d-Dimer, INR (international normalized ratio), platelet count and Antithrombin III will be drawn 15 minutes after the intervention is given, 4 hours and 24 hours later. The samples taken after the intervention are fully available for evaluation by the clinicians responsible for the patient. The patient will be observed with blood pressure, pulseoximetry, ECG and possible side effects or re-bleeding will be evaluated.

Follow up The patients will remain hospitalized for a minimum of 24 hours. We will contact all participants by phone six weeks after the intervention. Upon discharge from the hospital, all included patients receive information-material addressing possible late side effects and a contact number.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 249
• Est. completion date: July 2013
• Est. primary completion date: May 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Informed consent from participant.

2. Women who develop PPH defined as bleeding from uterus and/or the birth canal within 24 hours postpartum.

3. Age = 18 years.

4. If vaginal birth: indication of one of the following procedures at the operation theatre with anaesthetic assistance: a) Estimated blood loss = 500 ml and indication of manual removal of placenta or b) Indication of manual exploration of the uterus due to continuous bleeding after the birth of placenta.

5. If birth by Caesarean section: A perioperative blood loss = 1000 ml.

Exclusion Criteria:

1. Patients with known inherited deficiencies of coagulation.

2. Patients in anti-thrombotic treatment prepartum due to increased risk of thrombosis.

3. Patients with a pre-pregnancy weight <45 kg.

4. Patients who refuse to receive blood transfusion.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Hemorrhage
• Postpartum Haemorrhage
• Postpartum Hemorrhage

Intervention

Drug:
• Fibrinogen Concentrate
2 gram intra venous
• Isotonic Saline
Isotonic saline in equivalent volume - 100 ml

Locations

Country	Name	City	State
Denmark	Juliane Marie Centre, Rigshospitalet	Copenhagen	Capital Region
Denmark	University Hospital of Herlev	Herlev	Capital Region
Denmark	University Hospital of Hilleroed	Hilleroed	Capital Region
Denmark	University Hospital of Hvidovre	Hvidovre	Capital Region

Sponsors (14)

Lead Sponsor

Collaborator

Copenhagen University Hospital at Herlev

Aase and Ejnar Danielsens Foundation, Blood Bank of the Danish capital region, Copenhagen University Hospital, Hvidovre, Danish Council for Independent Research, Fonden til Lægevidenskabens Fremme, Haemonetics Corporation, Hans og Nora Buchards Fond, Herlev Hospital, Hillerod Hospital, Denmark, Laerdal Acute Foundation, Rigshospitalet, Denmark, The fund of 17-12-1981, Unit for monitoring of Good Clinical Practice Copenhagen University

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidense of transfusion with allogenic blood products		During hospital stay or until 6 weeks postintervention	No
Secondary	Severe Postpartum Haemorrhage (PPH)	Development of "Severe PPH" defined as: "Decrease of haemoglobin (Hb) of > 2,5 mmol/L, transfusion of at least 4 Red Blood Cell (RBC) units, haemostatic intervention (angiographic embolization, surgical arterial ligation or hysterectomy) or death.	During hospital stay or until 6 weeks postintervention	No
Secondary	Estimated blood loss		During hospital stay During hospital stay or until 6 weeks postintervention	No
Secondary	Total amount of blood transfused		During hospital stay During hospital stay or until 6 weeks postintervention	No
Secondary	The development of re-bleeding	Defined as bleeding reoccuring after primary haemostasis, and requiring surgical procedures or intervention	Untill follow-up 6 weeks postintervention	Yes
Secondary	Hemoglobin level below 3,6 mmol/L		During hospital stay or until 6 weeks postintervention	No
Secondary	Side-effects including thromboembolic complications	Safety measures/ Potential known side effects such as: Fever, headache, nausea, vomiting, allergic reactions, anaphylaxis and thrombo-embolic complications (deep venous thrombosis, acute myocardial infarct and lung embolus. All suspected unexpected serious adverse reactions will also be reported in accordance with the Good Clinical Practice (GCP) and the Danish Medicines Agency guidelines.	Untill 6 weeks postintervention	Yes