Post-Partum Hemorrhage
Conditions
Keywords
PPH, fibrinogen, vaginal delivery
Brief summary
The purpose 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, following vaginal delivery.
Detailed description
Randomised, double-blind,multicenter, placebo-controlled study
Interventions
Injection as soon as possible and within 30 min following the start of prostaglandin infusion
DRUGPlacebo
As soon as possible and within 30 min following the start of prostaglandin infusion
Sponsors
Laboratoire français de Fractionnement et de Biotechnologies
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Failure Rate of PPH Management | Evaluation of the two criteria that form the primary endpoint within the 48 h following the administration | The primary efficacy variable is a binary (Failure versus Success) composite endpoint. Failure is defined when a patient: * loses at least 4 g/dL of Hb compared to the reference Hb level , AND/OR * requires the transfusion of at least 2 units of packed RBCs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patients With at Least Administration of 2 Units of RBCs | from H0 to Day 2 | Considering failure as the fact of requiring at least 2 units of RBCs. |
| Patients With Loss of at Least 4 g/dL of Hb | From reference value to Day 2 | Considering failure as the fact of having lost at least 4 g/dL of Hb. |
Countries
France, Martinique
Participant flow
Recruitment details
Between 10 April 2014 and 20 June 2018, 448 patients from 30 sites signed an informed consent.
Pre-assignment details
During the pre-assigment period 11 patients withdrawn before treatment period. (1 treated with another IMP, 5 not treated, 2 no emergency consent signed, 1 no post inclusion consent signed, 2 refused to continue the study)
Participants by arm
| Arm | Count |
|---|---|
| Clottafact Human fibrinogen concentrate 3g intravenous use. 2 vials of 1,5 g/100mL, each vial of powder was reconstitued with 100 mL of sterile water for injection. | 224 |
| Placebo Placebo intravenous use. 2 vials of 100 mL, eache vial of powder was reconttitued with 100 mL of sterile water for injection. | 213 |
| Total | 437 |
Baseline characteristics
| Characteristic | Clottafact | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 224 Participants | 213 Participants | 437 Participants |
| Age, Continuous | 30.5 years STANDARD_DEVIATION 5.6 | 30.3 years STANDARD_DEVIATION 5.4 | 30.4 years STANDARD_DEVIATION 5.5 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 224 Participants | 213 Participants | 437 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 224 | 0 / 213 |
| other Total, other adverse events | 95 / 224 | 106 / 213 |
| serious Total, serious adverse events | 10 / 224 | 10 / 213 |
Outcome results
Primary
Failure Rate of PPH Management
The primary efficacy variable is a binary (Failure versus Success) composite endpoint. Failure is defined when a patient: * loses at least 4 g/dL of Hb compared to the reference Hb level , AND/OR * requires the transfusion of at least 2 units of packed RBCs.
Time frame: Evaluation of the two criteria that form the primary endpoint within the 48 h following the administration
Population: Number of patients with failure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Per Protocole (PP) Set Clottafact | Failure Rate of PPH Management | 75 Participants |
| Per Protocole (PP) Set Placebo | Failure Rate of PPH Management | 80 Participants |
| Intention To Treat (ITT) Set Clottafact | Failure Rate of PPH Management | 92 Participants |
| Intention To Treat (ITT) Set Placebo | Failure Rate of PPH Management | 92 Participants |
| Full Analysis Set (FAS) Clottafact | Failure Rate of PPH Management | 88 Participants |
| Full Analysis Set (FAS) Placebo | Failure Rate of PPH Management | 89 Participants |
p-value: 0.956395% CI: [0.6633, 1.4744]Regression, Logistic
Secondary
Patients With at Least Administration of 2 Units of RBCs
Considering failure as the fact of requiring at least 2 units of RBCs.
Time frame: from H0 to Day 2
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Per Protocole (PP) Set Clottafact | Patients With at Least Administration of 2 Units of RBCs | 51 Participants |
| Per Protocole (PP) Set Placebo | Patients With at Least Administration of 2 Units of RBCs | 52 Participants |
Comparison: Failure on individual component of the primary endpoint defined as administration of 2 units of RBCs.p-value: 0.978695% CI: [0.6321, 1.6022]Regression, Logistic
Secondary
Patients With Loss of at Least 4 g/dL of Hb
Considering failure as the fact of having lost at least 4 g/dL of Hb.
Time frame: From reference value to Day 2
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Per Protocole (PP) Set Clottafact | Patients With Loss of at Least 4 g/dL of Hb | 42 Participants |
| Per Protocole (PP) Set Placebo | Patients With Loss of at Least 4 g/dL of Hb | 41 Participants |
Comparison: Failure on individual component of the primary endpoint defined as a loss of at least 4 g/dL of Hb.p-value: 0.947495% CI: [0.6177, 1.6741]Regression, Logistic