FIB-PPH: Fibrinogen Concentrate as Initial Treatment for Postpartum Haemorrhage: A Randomised Clinically Controlled Trial
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2/Phase 3 |
Detailed 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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Fibrinogen Concentrate
|
Drug: Fibrinogen Concentrate
2 gram intra venous
Other Names:
|
| Placebo Comparator: Placebo Isotonic Saline |
Drug: Isotonic Saline
Isotonic saline in equivalent volume - 100 ml
|
Outcome Measures
Primary Outcome Measures
- Incidense of transfusion with allogenic blood products [During hospital stay or until 6 weeks postintervention]
Secondary Outcome Measures
- Severe Postpartum Haemorrhage (PPH) [During hospital stay or until 6 weeks postintervention]
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.
- Estimated blood loss [During hospital stay During hospital stay or until 6 weeks postintervention]
- Total amount of blood transfused [During hospital stay During hospital stay or until 6 weeks postintervention]
- The development of re-bleeding [Untill follow-up 6 weeks postintervention]
Defined as bleeding reoccuring after primary haemostasis, and requiring surgical procedures or intervention
- Hemoglobin level below 3,6 mmol/L [During hospital stay or until 6 weeks postintervention]
- Side-effects including thromboembolic complications [Untill 6 weeks postintervention]
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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Informed consent from participant.
-
Women who develop PPH defined as bleeding from uterus and/or the birth canal within 24 hours postpartum.
-
Age ≥ 18 years.
-
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.
-
If birth by Caesarean section: A perioperative blood loss ≥ 1000 ml.
Exclusion Criteria:
-
Patients with known inherited deficiencies of coagulation.
-
Patients in anti-thrombotic treatment prepartum due to increased risk of thrombosis.
-
Patients with a pre-pregnancy weight <45 kg.
-
Patients who refuse to receive blood transfusion.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Juliane Marie Centre, Rigshospitalet | Copenhagen | Capital Region | Denmark | 2100 |
| 2 | University Hospital of Herlev | Herlev | Capital Region | Denmark | 2730 |
| 3 | University Hospital of Hilleroed | Hilleroed | Capital Region | Denmark | 3400 |
| 4 | University Hospital of Hvidovre | Hvidovre | Capital Region | Denmark | 2650 |
Sponsors and Collaborators
- Copenhagen University Hospital at Herlev
- Rigshospitalet, Denmark
- Copenhagen University Hospital, Hvidovre
- Hillerod Hospital, Denmark
- Blood Bank of the Danish capital region
- Unit for monitoring of Good Clinical Practice Copenhagen University
- Danish Council for Independent Research
- Herlev Hospital
- Laerdal Foundation
- Aase and Ejnar Danielsens Foundation
- The Foundation of 17.12.1981
- Fonden til Lægevidenskabens Fremme
- Hans og Nora Buchards Fond
- Haemonetics Corporation
Investigators
- Principal Investigator: Anne J. Wikkelsoe, MD, Department of Anaesthesiology, University Hospital of Herlev, Denmark
- Study Chair: Ann M. Møller, MD, DmSc, Department of Anaesthesiology, University Hospital of Herlev, Denmark
- Study Chair: Jakob Stensballe, MD, PhD, Blood Bank of Danish Capital Region, Rigshospitalet
- Study Chair: Jens Langhoff-Roos, MD, DmSc, Department of Obstetrics, Juliane Marie Centre, Rigshospitalet
- Study Chair: Arash Afshari, MD, Department of Anaesthesiology, Juliane Marie Centre, Rigshospitalet, Denmark
- Study Chair: Hellen McKinnon Edwards, M.D., Dep. of Anaesthesiology, Herlev
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2009-017736-41
- 2009-017736-41
- 1002168
- 2612-4233
- 2007-58-0015-00911
- H-3-2010-004
- 2009-315