Postpartum HaemorrhagePhase 2/3FIB-PPHNCT01359878
Fibrinogen Concentrate as Initial Treatment for Postpartum Haemorrhage: A Randomised Clinically Controlled Trial
A Phase 2/3 study testing Fibrinogen Concentrate and Isotonic Saline in people with Postpartum Haemorrhage, run by Copenhagen University Hospital at Herlev at 4 sites in Denmark.
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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Postpartum Haemorrhage
- What is being tested?
- Fibrinogen Concentrate and Isotonic Saline
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 249 participants
- Where
- 4 sitesDenmark
- Study dates
- May 2011to Jul 2013
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
4 sites in 1 country.
Denmark4 sites
Juliane Marie Centre, Rigshospitalet
Copenhagen, Capital Region, 2100
University Hospital of Herlev
Herlev, Capital Region, 2730
University Hospital of Hilleroed
Hilleroed, Capital Region, 3400
University Hospital of Hvidovre
Hvidovre, Capital Region, 2650
About this study
Official title: Fibrinogen Concentrate as Initial Treatment for Postpartum Haemorrhage - A Randomised Clinically Controlled Trial
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.
Read more
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.
Read the 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.
- Conditions
- Postpartum Haemorrhage
- Being tested
- Fibrinogen Concentrate, Isotonic Saline
- Keywords
- Postpartum haemorrhage, Postpartum bleeding, Postnatal bleeding, Fibrinogen concentrate, Transfusion, Haemostatis, Thrombelastography
- Medical subject headings
- Postpartum Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fibrinogen ConcentrateDrug
Also called Haemocomplettan, CSL Behring
2 gram intra venous
Isotonic SalineDrug
Isotonic saline in equivalent volume - 100 ml
| Study group | Role | What they receive |
|---|---|---|
| Fibrinogen Concentrate | Experimental | Not described Receives: Drug: Fibrinogen Concentrate |
| Placebo | Placebo comparator | Isotonic Saline Receives: Drug: Isotonic Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidense of transfusion with allogenic blood products
Measured: During hospital stay or until 6 weeks postintervention
Secondary outcomes (6)
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.
Measured: During hospital stay or until 6 weeks postintervention
Estimated blood loss
Measured: During hospital stay During hospital stay or until 6 weeks postintervention
Total amount of blood transfused
Measured: During hospital stay During hospital stay or until 6 weeks postintervention
The development of re-bleeding
Defined as bleeding reoccuring after primary haemostasis, and requiring surgical procedures or intervention
Measured: Untill follow-up 6 weeks postintervention
Hemoglobin level below 3,6 mmol/L
Measured: During hospital stay or until 6 weeks postintervention
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.
Measured: Untill 6 weeks postintervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2011 (estimated)
- Study startMay 2011
- Primary completionMay 2013
- Study completionJul 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Postpartum HaemorrhageStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 249 participants (actual)
Sponsor and investigators
- Lead sponsor
- Copenhagen University Hospital at Herlev
- Sponsor type
- University, hospital or other
- Collaborators
- Copenhagen University Hospital, Rigshospitalet, 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
- Responsible party
- Principal investigator, Anne Juul Wikkelsø, Copenhagen University Hospital at Herlev
- Investigators
- Anne J. Wikkelsoe, MD, Principal investigator, Department of Anaesthesiology, University Hospital of Herlev, DenmarkAnn M. Møller, MD, DmSc, Study chair, Department of Anaesthesiology, University Hospital of Herlev, DenmarkJakob Stensballe, MD, PhD, Study chair, Blood Bank of Danish Capital Region, RigshospitaletJens Langhoff-Roos, MD, DmSc, Study chair, Department of Obstetrics, Juliane Marie Centre, RigshospitaletArash Afshari, MD, Study chair, Department of Anaesthesiology, Juliane Marie Centre, Rigshospitalet, DenmarkHellen McKinnon Edwards, M.D., Study chair, Dep. of Anaesthesiology, Herlev
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01359878
- Sponsor's protocol ID
- 2009-017736-41
- Other IDs
- 2009-017736-41, 1002168, 2612-4233, 2007-58-0015-00911, H-3-2010-004, 2009-315, 2009
- Acronym
- FIB-PPH
- Status last verified
- Sep 2013
- First submitted
- 20 May 2011
- Last updated
- 20 Sep 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Wikkelso AJ, Edwards HM, Afshari A, Stensballe J, Langhoff-Roos J, Albrechtsen C, Ekelund K, Hanke G, Secher EL, Sharif HF, Pedersen LM, Troelstrup A, Lauenborg J, Mitchell AU, Fuhrmann L, Svare J, Madsen MG, Bodker B, Moller AM; FIB-PPH trial group. Pre-emptive treatment with fibrinogen concentrate for postpartum haemorrhage: randomized controlled trial. Br J Anaesth. 2015 Apr;114(4):623-33. doi: 10.1093/bja/aeu444. Epub 2015 Jan 13.
PubMed 25586727Wikkelsoe AJ, Afshari A, Stensballe J, Langhoff-Roos J, Albrechtsen C, Ekelund K, Hanke G, Sharif HF, Mitchell AU, Svare J, Troelstrup A, Pedersen LM, Lauenborg J, Madsen MG, Bodker B, Moller AM. The FIB-PPH trial: fibrinogen concentrate as initial treatment for postpartum haemorrhage: study protocol for a randomised controlled trial. Trials. 2012 Jul 17;13:110. doi: 10.1186/1745-6215-13-110.
PubMed 22805300
Study at a glance
From the registry record, last updated by the sponsor on 20 Sep 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fibrinogen Concentrate as Initial Treatment for Postpartum Haemorrhage - A Randomised Clinically Controlled Trial
- ClinicalTrials.gov ID
- NCT01359878
- Acronym / sponsor ID
- FIB-PPH / 2009-017736-41
- Conditions
- Postpartum Haemorrhage
- Keywords
- Postpartum haemorrhage, Postpartum bleeding, Postnatal bleeding, Fibrinogen concentrate, Transfusion, Haemostatis, Thrombelastography
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 249 participants (actual)
- Lead sponsor
- Copenhagen University Hospital at HerlevUniversity, hospital or other
- Collaborators
- Copenhagen University Hospital, Rigshospitalet, 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
- Study start
- May 2011
- Primary completion
- May 2013 (actual)
- Study completion
- Jul 2013 (actual)
- First posted
- 25 May 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fibrinogen Concentrate | Experimental | Drug: Fibrinogen Concentrate |
| Placebo | Placebo comparator | Drug: Isotonic SalineIsotonic Saline |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fibrinogen ConcentrateAlso: Haemocomplettan, CSL Behring2 gram intra venous | Drug | Fibrinogen Concentrate |
| Isotonic SalineIsotonic saline in equivalent volume - 100 ml | Drug | Placebo |
Primary outcome
Incidense of transfusion with allogenic blood products
Time frame: During hospital stay or until 6 weeks postintervention
6 secondary outcomes
Severe Postpartum Haemorrhage (PPH)
Time frame: During hospital stay or until 6 weeks postintervention
Estimated blood loss
Time frame: During hospital stay During hospital stay or until 6 weeks postintervention
Total amount of blood transfused
Time frame: During hospital stay During hospital stay or until 6 weeks postintervention
The development of re-bleeding
Time frame: Untill follow-up 6 weeks postintervention
Hemoglobin level below 3,6 mmol/L
Time frame: During hospital stay or until 6 weeks postintervention
Side-effects including thromboembolic complications
Time frame: Untill 6 weeks postintervention
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Sep 2013.
- Derived from this study: PubMed 25586727Wikkelso AJ, Edwards HM, Afshari A, Stensballe J, Langhoff-Roos J, Albrechtsen C, Ekelund K, Hanke G, Secher EL, Sharif HF, Pedersen LM, Troelstrup A, Lauenborg J, Mitchell AU, Fuhrmann L, Svare J, Madsen MG, Bodker B, Moller AM; FIB-PPH trial group. Pre-emptive treatment with fibrinogen concentrate for postpartum haemorrhage: randomized controlled trial. Br J Anaesth. 2015 Apr;114(4):623-33. doi: 10.1093/bja/aeu444. Epub 2015 Jan 13.
- Derived from this study: PubMed 22805300Wikkelsoe AJ, Afshari A, Stensballe J, Langhoff-Roos J, Albrechtsen C, Ekelund K, Hanke G, Sharif HF, Mitchell AU, Svare J, Troelstrup A, Pedersen LM, Lauenborg J, Madsen MG, Bodker B, Moller AM. The FIB-PPH trial: fibrinogen concentrate as initial treatment for postpartum haemorrhage: study protocol for a randomised controlled trial. Trials. 2012 Jul 17;13:110. doi: 10.1186/1745-6215-13-110.
Related trials for Postpartum Haemorrhage
Not yet recruiting
Comparison of Effect of Two Different Doses of Intravenous Oxytocin on Patients Undergoing Elective Cesarean Section
Postpartum Hemorrhage, Uterine Atony
RecruitingPhase 3
Tranexamic Acid to Prevent Heavy Bleeding After Childbirth in Women at Higher Risk
Postpartum Hemorrhage
Not yet recruitingObservational study
Measured Versus Hemoglobin-Calculated Postpartum Blood Loss in Waterbirth
Postpartum Hemorrhage, Waterbirth
RecruitingObservational study
Long Term Outcome After Use of Vacuum-induced Tamponade for Postpartum Hemorrhage
Postpartum Hemorrhage, Treatment Outcome
RecruitingPhase 2
Prevention of Postpartum Hemorrhage With Tranexamic Acid
Post Partum Hemorrhage
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anne J. Wikkelsoe, MD principal investigator
Department of Anaesthesiology, University Hospital of Herlev, Denmark
Ann M. Møller, MD, DmSc study chair
Department of Anaesthesiology, University Hospital of Herlev, Denmark
Jakob Stensballe, MD, PhD study chair
Blood Bank of Danish Capital Region, Rigshospitalet
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Fibrinogen Concentrate and Isotonic Saline in people with Postpartum Haemorrhage, run by Copenhagen University Hospital at Herlev at 4 sites in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Sep 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidense of transfusion with allogenic blood products (time frame: During hospital stay or until 6 weeks postintervention). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01359878, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Sep 2013.