Fibrinogen Concentrate as Initial Treatment for Postpartum Haemorrhage: A Randomised Clinically Controlled Trial (FIB-PPH)

This study has been completed.
Sponsor:
Collaborators:
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
The research council of University Hospital Herlev
Laerdal Acute Foundation
Aase og Ejnar Danielsens fund
The fund of 17-12-1981
Fonden til Lægevidenskabens Fremme
Hans og Nora Buchards Fond
Haemonetics Corporation
Information provided by (Responsible Party):
Anne Juul Wikkelsø, Copenhagen University Hospital at Herlev
ClinicalTrials.gov Identifier:
NCT01359878
First received: May 20, 2011
Last updated: September 19, 2013
Last verified: September 2013
  Purpose

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 Intervention Phase
Postpartum Haemorrhage
Drug: Fibrinogen Concentrate
Drug: Isotonic Saline
Phase 2
Phase 3

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Copenhagen University Hospital at Herlev:

Primary Outcome Measures:
  • Incidense of transfusion with allogenic blood products [ Time Frame: During hospital stay or until 6 weeks postintervention ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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.


Enrollment: 249
Study Start Date: May 2011
Study Completion Date: July 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fibrinogen Concentrate Drug: Fibrinogen Concentrate
2 gram intra venous
Other Name: Haemocomplettan, CSL Behring
Placebo Comparator: Placebo
Isotonic Saline
Drug: Isotonic Saline
Isotonic saline in equivalent volume - 100 ml

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01359878

Locations
Denmark
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
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
The research council of University Hospital Herlev
Laerdal Acute Foundation
Aase og Ejnar Danielsens fund
The fund 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
  More Information

Additional Information:
No publications provided by Copenhagen University Hospital at Herlev

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Anne Juul Wikkelsø, MD, Copenhagen University Hospital at Herlev
ClinicalTrials.gov Identifier: NCT01359878     History of Changes
Other Study ID Numbers: 2009-017736-41, 2009-017736-41, 1002168, 2612-4233, 2007-58-0015-00911, H-3-2010-004, 2009-315
Study First Received: May 20, 2011
Last Updated: September 19, 2013
Health Authority: Denmark: Danish Dataprotection Agency
Denmark: Danish Medicines Agency
Denmark: The Danish National Committee on Biomedical Research Ethics
Denmark: The Regional Committee on Biomedical Research Ethics

Keywords provided by Copenhagen University Hospital at Herlev:
Postpartum haemorrhage
Postpartum bleeding
Postnatal bleeding
Fibrinogen concentrate
Transfusion
Haemostatis
Thrombelastography

Additional relevant MeSH terms:
Hemorrhage
Postpartum Hemorrhage
Pathologic Processes
Obstetric Labor Complications
Pregnancy Complications
Puerperal Disorders
Uterine Hemorrhage

ClinicalTrials.gov processed this record on July 26, 2014