Fibrinogen Concentrate as Initial Treatment for Postpartum Haemorrhage: A Randomised Clinically Controlled Trial (FIB-PPH)
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.
Drug: Fibrinogen Concentrate
Drug: Isotonic Saline
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
|Official Title:||Fibrinogen Concentrate as Initial Treatment for Postpartum Haemorrhage - A Randomised Clinically Controlled Trial|
- Incidense of transfusion with allogenic blood products [ Time Frame: During hospital stay or until 6 weeks postintervention ] [ Designated as safety issue: No ]
- Severe Postpartum Haemorrhage (PPH) [ Time Frame: During hospital stay or until 6 weeks postintervention ] [ Designated as safety issue: No ]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 [ Time Frame: During hospital stay During hospital stay or until 6 weeks postintervention ] [ Designated as safety issue: No ]
- Total amount of blood transfused [ Time Frame: During hospital stay During hospital stay or until 6 weeks postintervention ] [ Designated as safety issue: No ]
- The development of re-bleeding [ Time Frame: Untill follow-up 6 weeks postintervention ] [ Designated as safety issue: Yes ]Defined as bleeding reoccuring after primary haemostasis, and requiring surgical procedures or intervention
- Hemoglobin level below 3,6 mmol/L [ Time Frame: During hospital stay or until 6 weeks postintervention ] [ Designated as safety issue: No ]
- Side-effects including thromboembolic complications [ Time Frame: Untill 6 weeks postintervention ] [ Designated as safety issue: Yes ]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.
|Study Start Date:||May 2011|
|Study Completion Date:||July 2013|
|Primary Completion Date:||May 2013 (Final data collection date for primary outcome measure)|
|Experimental: Fibrinogen Concentrate||
Drug: Fibrinogen Concentrate
2 gram intra venous
Other Name: Haemocomplettan, CSL Behring
Placebo Comparator: Placebo
Drug: Isotonic Saline
Isotonic saline in equivalent volume - 100 ml
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01359878
|Juliane Marie Centre, Rigshospitalet|
|Copenhagen, Capital Region, Denmark, 2100|
|University Hospital of Herlev|
|Herlev, Capital Region, Denmark, 2730|
|University Hospital of Hilleroed|
|Hilleroed, Capital Region, Denmark, 3400|
|University Hospital of Hvidovre|
|Hvidovre, Capital Region, Denmark, 2650|
|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|