A Program to Evaluate Riastap® and FIBTEM® for the Early Control and Treatment of Postpartum Hemorrhage (PERFECT PPH)

Study Overview
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Brief Summary
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In this prospective, single-center, randomized, placebo-controlled, double-blind clinical trial, parturients with primary PPH are eligible for treatment with fibrinogen concentrate following both vaginal delivery and cesarean section complicated by an estimated blood loss (EBL) >1000 mL and an ongoing bleeding notwithstanding standard treatment measures (volume replacement, uterine massage, and uterotonic agents).

Detailed Description
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The proposed trial targets early detection and treatment of fibrinogen depletion in PPH. A widespread belief in the benefits of early fibrinogen substitution in cases of PPH has led to an increased use for this indication. The PERFECT PPH aims to provide an evidence-based knowledge for the recommendation of the early use of fibrinogen concentrate in PPH.

Official Title
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A Program to Evaluate Riastap® and FIBTEM® for the Early Control and Treatment of Postpartum Hemorrhage (PERFECT PPH)

Conditions
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Postpartum Hemorrhage

Intervention / Treatment
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* Drug: fibrinogen concentrate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent from participant Age ≥18 years and <50 years Primary PPH defined as bleeding from uterus and/or the birth canal within 24 hours postpartum Vaginal delivery or Cesarean delivery (irrespective of etiology of PPH, such as accreta), with EBL >1000 mL and ongoing bleeding notwithstanding standard treatment measures (volume replacement, uterine massage, uterotonic agents) FIBTEM®- A10 <18 mm (corresponding to a MCF value of <20 mm and to a plasma fibrinogen level approximately <3 g/L) Exclusion Criteria: Refusal to give written informed consent Refusal to receive blood transfusion Known inherited deficiencies of coagulation Personal history of thrombosis Either pre-pregnancy or ante-partum antithrombotic treatment due to increased risk of thrombosis Administration of Platelets, FFP or cryotherapy prior to study drug

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>At the same time of randomization code generation, blood samples for a baseline ROTEM® analysis will be drawn, and blood products will be ordered. Patients will be eligible to receive study drug (fibrinogen concentrate or 0.9% saline solution), according to the randomization code previously generated, only if FIBTEM® - A10 value is <18 mm (corresponding to a MCF value of <20 mm, that is a plasma fibrinogen level <3 g/L). | Drug: Placebo<br>* 0.9% saline solution<br>* Other names: saline;|
| Experimental: Fibrinogen concentrate<br>At the same time of randomization code generation, blood samples for a baseline ROTEM® analysis will be drawn, and blood products will be ordered. Patients will be eligible to receive study drug (fibrinogen concentrate or 0.9% saline solution), according to the randomization code previously generated, only if FIBTEM® - A10 value is <18 mm (corresponding to a MCF value of <20 mm, that is a plasma fibrinogen level <3 g/L). | Drug: fibrinogen concentrate<br>* The dose of fibrinogen concentrate needed to achieve this target will be calculated using a formula that accounts for the baseline FIBTEM® - A10 value and the patient's body weight assessed at hospital admission . In general, a 70-kg patient requires a fibrinogen dose of approximately 0.5 g to increase the MCF by approximately 1 mm.<br>* Other names: Riastap;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| maximum clot firmness (MCF via FIBTEM A10) | fib-tem® is a ready-to-use ROTEM® system reagent for use with citrated whole blood. It assesses the clot firmness of the fibrin clot. This is influenced mainly by the fibrinogen- and F XIII levels of the blood sample and by fibrin polymerisation disorders. The reagent contains a powerful platelet inhibitor; therefore only a fibrin clot is formed and measured. MCF is measured as the maximal amplitude of the curve. | 15 minutes | 
| maximum clot firmness (MCF via FIBTEM A10) | fib-tem® is a ready-to-use ROTEM® system reagent for use with citrated whole blood. It assesses the clot firmness of the fibrin clot. This is influenced mainly by the fibrinogen- and F XIII levels of the blood sample and by fibrin polymerisation disorders. The reagent contains a powerful platelet inhibitor; therefore only a fibrin clot is formed and measured. MCF is measured as the maximal amplitude of the curve. | 1 hour | 
| maximum clot firmness (MCF via FIBTEM A10) | fib-tem® is a ready-to-use ROTEM® system reagent for use with citrated whole blood. It assesses the clot firmness of the fibrin clot. This is influenced mainly by the fibrinogen- and F XIII levels of the blood sample and by fibrin polymerisation disorders. The reagent contains a powerful platelet inhibitor; therefore only a fibrin clot is formed and measured. MCF is measured as the maximal amplitude of the curve. | 6 hours | 
| maximum clot firmness (MCF via FIBTEM A10) | fib-tem® is a ready-to-use ROTEM® system reagent for use with citrated whole blood. It assesses the clot firmness of the fibrin clot. This is influenced mainly by the fibrinogen- and F XIII levels of the blood sample and by fibrin polymerisation disorders. The reagent contains a powerful platelet inhibitor; therefore only a fibrin clot is formed and measured. MCF is measured as the maximal amplitude of the curve. | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fibrinogen concentrate, coagulation