Study on the efficacy and safety of a therapeutic strategy of post partum haemorrhage comparing early administration of human fibrinogen versus placebo in patients treated with intravenous prostaglandins following vaginal delivery.

• Register: EUCTR
• Last refreshed on: 17 September 2018
• Main ID: EUCTR2013-002484-26-FR
• Date of registration: 24/09/2015
• Prospective Registration: No
• Primary sponsor: LFB Biomédicaments
• Public title: Study on the efficacy and safety of a therapeutic strategy of post partum haemorrhage comparing early administration of human fibrinogen versus placebo in patients treated with intravenous prostaglandins following vaginal delivery.
• Scientific title: A RANDOMISED, MULTICENTRE, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY ON THE EFFICACY AND SAFETY OF A THERAPEUTIC STRATEGY OF POST PARTUM HAEMORRHAGE COMPARING EARLY ADMINISTRATION OF HUMAN FIBRINOGEN VERSUS PLACEBO IN PATIENTS TREATED WITH INTRAVENOUS PROSTAGLANDINS FOLLOWING VAGINAL DELIVERY.
• Date of first enrolment: 18/08/2014
• Target sample size: 434
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-002484-26
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

France

Contacts

• Name: Clinical Project Manager
• Affiliation: LFB Biomédicaments

• Name: Clinical Project Manager
• Affiliation: LFB Biomédicaments

Key inclusion & exclusion criteria

Inclusion criteria:
•Signed and dated informed consent form
•Vaginal delivery
•PPH requiring IV administration of prostaglandins
•At least one available result of Hb level during the third trimester of pregnancy
•18-year old female patients and older
•Covered by healthcare insurance in accordance with local requirements

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 434
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
•Caesarean section
•Haemostatic intervention (as ligation, embolization or hysterectomy) already decided at the time of inclusion
•Known placenta praevia or accreta
•Hb level < 10g/dl during the third trimester of pregnancy
•History of venous or arterial thromboembolic event
•Known inherited bleeding or thrombotic disorders
•Treatment with low-molecular-weight heparin (LMWH) within 24 hours prior to the inclusion
•Treatment with acetylsalicylic acid within 5 days prior to the inclusion
•Treatment with vitamin K antagonists within 7 days prior to the inclusion
•Administration of fibrinogen concentrate within 48 hours prior to the inclusion
•Administration of FFP, platelets units or prohaemostatic drugs,
tranexamic acid and rFVIIa or prothrombin complex concentrates
(PCC) within 48 hours prior to the inclusion
•Administration of RBCs within 3 months prior to the inclusion
•Participation in another interventional clinical study within 30 days prior to the inclusion
•Previous inclusion/enrolment in the present clinical study
•Known history of hypersensitivity or other severe reaction to any component of Clottafact® or placebo
•Minors, majors under guardianship, persons staying in health or social institutes and people deprived of their freedom
•Known drug or alcohol abuse
•Patients whose use of concomitant medication may interfere with the interpretation of data
•Any other current significant medical condition that might interfere with treatment evaluation according to the investigator’s judgement
•Patients who are unlikely to survive through the treatment period and evaluation
•Patients transferred from another service



Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

post partum haemorrhage following vaginal delivery
MedDRA version: 18.0 Level: LLT Classification code 10036294 Term: Postpartum haemorrhage (primary) System Organ Class: 100000004868

Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Intervention(s)

Trade Name: CLOTTAFACT 1.5g/100ml
Product Name: Clottafact
Product Code: FGTW
Pharmaceutical Form: Powder and solvent for solution for injection
Pharmaceutical form of the placebo: Powder and solvent for solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: 48h following the IMP administration.

Secondary Objective: The secondary objectives are:
•To assess the evolution of haemorrhage
•To assess the need for haemostatic intervention
•To assess the maternal morbi-mortality
•To assess the biological effects of fibrinogen concentrate administration
•To assess the tolerance of fibrinogen concentrate administration

Main Objective: The primary objectve of the study is to assess the benefits of a therapeutic strategy that associates an early administration of human fibrinogen concentrate in the management of PPH on the reduction of bleeding after the initiation of prostaglandins intravenous infusion.

Primary end point(s): Percentage of patients losing at least 4 g/dl of Hb, and/or requiring the transfusion of at least 2 units of packed RBCs within the 48 hours following the administration of IMP.
The reference for Hb level is the most recent value recorded during the third trimester of pregnancy.

Secondary Outcome(s)

Secondary end point(s): - Evolution of haemorrhage
oPercentage of patients losing at least 4 g/dL of Hb, 48 hours following IMP administration with regards to the Hb reference level.
oPercentage of patients losing at least 3 g/dL of Hb, 48 hours following the IMP administration with regards to the Hb reference level.
oPercentage of patients requiring the transfusion of at least 2 units of packed RBCs, 48 hours following the IMP administration.
oPercentage of patients losing at least 4 g/dL of Hb, 48 hours following the IMP administration with regards to the Hb level measured at inclusion.
oPercentage of patients with an occurrence of Hb level < 9 g/dL within the 48 hours period following inclusion.
oNumber of units of transfused blood products within the 48 hours period following the IMP administration.
oCalculated volume of total blood loss, 48 hours following the IMP administration.

- Need for haemostatic intervention
oPercentage of patients requiring at least one of the following interventions within 48 hours following the administration of IMP: uterine ligation (B Lynch or other techniques), pelvic arteries embolization, surgical vascular ligation, administration of recombinant activated Factor VII (rFVIIa) and hysterectomy.

- Maternal morbi-mortality
oLength of stay in resuscitation and/or intensive care and/or PICU and/or continuous care
oLength of stay in obstetrics units
oSingle or multi-organ failure (SOFA) score in women transferred to resuscitation and/or intensive care and/or PICU and/or continuous care units
oDeath during the study

- Evolution of blood fibrinogen level after early administration
oChange in plasma fibrinogen level between H0 (start of IMP infusion) and D2.

- Evolution of hemoconcentration
oChange in Hb level between each determination and H0
oChange in Ht level between each determination and H0
oChange in RBCs count between each determination and H0

Timepoint(s) of evaluation of this end point: The timepoints of evaluation of secondary endpoints are variable and are defined for each endpoint.

Secondary ID(s)

FIDEL

Source(s) of Monetary Support

LFB Biomédicaments