Haemostasis and Tranexamic Acid in Caesarean Delivery

Study Overview
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Brief Summary
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The aim of the study is to evaluate haemostasis and fibrinolysis in peripartum of caesarean delivery and the effect of tranexamic acid (TXA) given in prevention of post-partum haemorrhage (PPH).

Detailed Description
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Post-partum haemorrhage (PPH) remains a leading cause of maternal morbidity and mortality. Haemostasis and fibrinolysis are activated in peripartum. Fibrinolysis is decreased during pregnancy, is quickly activated after childbirth and can be overactivated in case of PPH. Tranexamic acid (TXA), an antifibrinolytic drug, has been proven to efficiently decrease bleeding and death in PPH. Its place in prevention of PPH after caesarean section remains to be established. The aim of the study protocol TRAAP2 is to conduct a large multicentre randomized, double blind placebo-controlled trial to adequately assess the impact of TXA for preventing PPH following a caesarean section. Peripartum is also a period of increased thrombo-embolic risk. TXA has never been proven to increase thromboembolic events. Nevertheless, it seems important to reserve TXA for women with activated fibrinolysis. The aim of the ancillary biologic study BIO-TRAAP is thus to explore haemostasis and fibrinolysis in peripartum, to determine which women will in the future benefit from TXA. Fibrinolysis will be studied by clot lysis time by Global Fibrinolytic Capacity test on the Lysis Timer (GFC/LT), t-PA, PAI-1, PAI-2, euglobulin clot lysis time, plasminogen, plasmin-anti-plasmin complex, thrombin-anti-thrombin complex, fibrin degradation products (FDP).

Official Title
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Study of Peripartum Haemostasis and Effects of Tranexamic Acid in Caesarean Delivery: Biologic Ancillary Study in TRAAP2 Patients Recruited at the Bordeaux University Hospital: BIO-TRAAP

Conditions
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Postpartum Hemorrhage, Hyperfibrinolysis

Intervention / Treatment
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* Diagnostic Test: peripartum haemostasis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patient randomized into TRAAP2 study (NCT03431805): adult women admitted for a planned caesarean delivery, at term ≥ 34 weeks, haemoglobin level at the last blood sample >9g/dl, blood Formula numbering within 7 days before caesarean delivery, informed signed consent) informed signed consent for BIO-TRAAP Exclusion Criteria: patient not included into TRAAP2 study: previous thrombotic event or pre-existing pro-thrombotic disease, epileptic state or history of seizures, presence of any chronic or active cardiovascular disease outside hypertension, any chronic or active renal disease including renal, chronic or acute insufficiency (glomerular flow <90mL / min), and chronic or active liver disease at risk thrombotic or haemorrhagic, autoimmune disease, sickle cell disease, placenta praevia, placenta accreta/increta/percreta, abruption placentae, eclampsia, HELLP syndrome, in utero fetal death, administration of low-molecular-weight heparin or antiplatelet agents during the week before delivery, general anaesthesia, hypersensitivity to tranexamic acid or concentrated hydrochloric acid, instrumental extraction failure, multiple pregnancy with genital delivery of the first twin and caesarean delivery for the second or at third trimester, poor understanding of the French language

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Three blood samples of 20 ml each at T0 after the anesthesia for the caesarean section and before the administration of the product (TXA or placebo), T15 fifteen minutes after the administration of the product and T120, 2 hours after the administration of TRAAP2 study IMP (tranexamic acid or placebo).
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tranexamic acid<br>intravenous administration of 10-mL of tranexamic acid (EXACYL® 1 g/10 ml I.V., solution injectable) | Diagnostic Test: peripartum haemostasis<br>* Three blood samples of 20 ml each at T0 after the anaesthesia for the caesarean section and before the administration of the product (TXA or placebo), T15 fifteen minutes after the administration of the product and T120, 2 hours after the administration of the product.<br>|
| Placebo Comparator: Chloride solution<br>sodium intravenous administration of 10-mL of chloride solution (0.9% -10mL) | Diagnostic Test: peripartum haemostasis<br>* Three blood samples of 20 ml each at T0 after the anaesthesia for the caesarean section and before the administration of the product (TXA or placebo), T15 fifteen minutes after the administration of the product and T120, 2 hours after the administration of the product.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clot lysis time | Clot lysis time in minutes studied by the Global Fibrinolytic Capacity on the Lysis Timer | Baseline (defined as the time of insertion of the peripheric venous line) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lysis Timer clot lysis time | Clot lysis time in minutes studied by the Global Fibrinolytic Capacity on the Lysis Timer | Time 15min and Time 120min (defined as 15 minutes 120 minutes after the administration of the product, respectively) | 
| Routine clot lysis time | Clot lysis time in minutes studied by the routine biological tests | Baseline, Time 15min, and Time 120min | 
| t-PA | tissue-Plasminogen Activator (ng/ml) | Baseline, Time 15min, and Time 120min | 
| PAI-1 | Plasminogen activator inhibitor-1 (ng/ml) | Baseline, Time 15min, and Time 120min | 
| PAI-2 | Plasminogen activator inhibitor-2 (ng/ml) | Baseline, Time 15min, and Time 120min | 
| Euglobulin clot lysis time | Euglobulin clot lysis time (min), | Baseline, Time 15min, and Time 120min | 
| Plasminogen | Plasminogen (%) | Baseline, Time 15min, and Time 120min | 
| Hb | Hemoglobin (g/dl) | Baseline, Time 15min, and Time 120min | 
| Platelets | Platelets (G/l) | Baseline, Time 15min, and Time 120min | 
| TP | Prothrombin ratio (%) | Baseline, Time 15min, and Time 120min | 
| aPTT ratio | Activated Cephalin Time (sec) | Baseline, Time 15min, and Time 120min | 
| Fibrinogen | Fibrinogen (g/l) | Baseline, Time 15min, and Time 120min | 
| Fibrin degradation products | Fibrin degradation products (µg/l) | Baseline, Time 15min, and Time 120min | 
| Plasmin-antiplasmin complex | Plasmin-antiplasmin complex (µg/l) | Baseline, Time 15min, and Time 120min | 
| Thrombin-antithrombin complex | Thrombin-antithrombin complex (ng/ml) | Baseline, Time 15min, and Time 120min | 
| Bleeding | Bleeding (ml) | Baseline, Time 15min, and Time 120min | 
| Transfusion of packs of red blood cells | Number of packs of red blood cells | Time 120min | 
| Transfusion of platelet concentrates | Number of platelet concentrates | Time 120min | 
| Transfusion of plasma | volume of plasma (ml) | Time 120min | 
| Transfusion of fibrinogen concentrate | Amount (g) of fibrinogen concentrate | Time 120min | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ancillary biologic study, fibrinolysis, tranexamic acid, post-partum haemorrhage