Haemostasis and Tranexamic Acid in Caesarean Delivery (BIO-TRAAP)

• ClinicalTrials.gov Identifier: NCT03742947
• Recruitment Status: Completed
• First Posted: November 15, 2018
• Last Update Posted: April 29, 2020
• Sponsor: University Hospital, Bordeaux
• Collaborators: Bordeaux Association for Training and Research in Obstetric Gynecology; Association of Anesthesiologists and Intensivists of Vascular Surgery and Transplantation
• Information provided by (Responsible Party): University Hospital, Bordeaux

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Postpartum Hemorrhage; Hyperfibrinolysis	Diagnostic Test: peripartum haemostasis	Not Applicable

Detailed Description:

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).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 34 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention 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 (Participant, Investigator)
• Masking Description: Double blind
• Primary Purpose: Diagnostic
• Official Title: 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
• Actual Study Start Date: January 10, 2019
• Actual Primary Completion Date: January 17, 2020
• Actual Study Completion Date: January 17, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Tranexamic acid; intravenous administration of 10-mL of tranexamic acid (EXACYL® 1 g/10 ml I.V., solution injectable)	Diagnostic Test: peripartum haemostasis; 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.
Placebo Comparator: Chloride solution; sodium intravenous administration of 10-mL of chloride solution (0.9% -10mL)	Diagnostic Test: peripartum haemostasis; 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.

Outcome Measures

Primary Outcome Measures :

1. Clot lysis time [ Time Frame: Baseline (defined as the time of insertion of the peripheric venous line) ]
   Clot lysis time in minutes studied by the Global Fibrinolytic Capacity on the Lysis Timer

Secondary Outcome Measures :

1. Lysis Timer clot lysis time [ Time Frame: Time 15min and Time 120min (defined as 15 minutes 120 minutes after the administration of the product, respectively) ]
   Clot lysis time in minutes studied by the Global Fibrinolytic Capacity on the Lysis Timer
2. Routine clot lysis time [ Time Frame: Baseline, Time 15min, and Time 120min ]
   Clot lysis time in minutes studied by the routine biological tests
3. t-PA [ Time Frame: Baseline, Time 15min, and Time 120min ]
   tissue-Plasminogen Activator (ng/ml)
4. PAI-1 [ Time Frame: Baseline, Time 15min, and Time 120min ]
   Plasminogen activator inhibitor-1 (ng/ml)
5. PAI-2 [ Time Frame: Baseline, Time 15min, and Time 120min ]
   Plasminogen activator inhibitor-2 (ng/ml)
6. Euglobulin clot lysis time [ Time Frame: Baseline, Time 15min, and Time 120min ]
   Euglobulin clot lysis time (min),
7. Plasminogen [ Time Frame: Baseline, Time 15min, and Time 120min ]
   Plasminogen (%)
8. Hb [ Time Frame: Baseline, Time 15min, and Time 120min ]
   Hemoglobin (g/dl)
9. Platelets [ Time Frame: Baseline, Time 15min, and Time 120min ]
   Platelets (G/l)
10. TP [ Time Frame: Baseline, Time 15min, and Time 120min ]
    Prothrombin ratio (%)
11. aPTT ratio [ Time Frame: Baseline, Time 15min, and Time 120min ]
    Activated Cephalin Time (sec)
12. Fibrinogen [ Time Frame: Baseline, Time 15min, and Time 120min ]
    Fibrinogen (g/l)
13. Fibrin degradation products [ Time Frame: Baseline, Time 15min, and Time 120min ]
    Fibrin degradation products (µg/l)
14. Plasmin-antiplasmin complex [ Time Frame: Baseline, Time 15min, and Time 120min ]
    Plasmin-antiplasmin complex (µg/l)
15. Thrombin-antithrombin complex [ Time Frame: Baseline, Time 15min, and Time 120min ]
    Thrombin-antithrombin complex (ng/ml)
16. Bleeding [ Time Frame: Baseline, Time 15min, and Time 120min ]
    Bleeding (ml)
17. Transfusion of packs of red blood cells [ Time Frame: Time 120min ]
    Number of packs of red blood cells
18. Transfusion of platelet concentrates [ Time Frame: Time 120min ]
    Number of platelet concentrates
19. Transfusion of plasma [ Time Frame: Time 120min ]
    volume of plasma (ml)
20. Transfusion of fibrinogen concentrate [ Time Frame: Time 120min ]
    Amount (g) of fibrinogen concentrate

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

France

CHU Bordeaux

Bordeaux, France, 33000

Sponsors and Collaborators

University Hospital, Bordeaux

Bordeaux Association for Training and Research in Obstetric Gynecology

Association of Anesthesiologists and Intensivists of Vascular Surgery and Transplantation

More Information

• Responsible Party: University Hospital, Bordeaux
• ClinicalTrials.gov Identifier: NCT03742947
• Other Study ID Numbers: CHUBX 2018/24
• First Posted: November 15, 2018
• Last Update Posted: April 29, 2020
• Last Verified: April 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University Hospital, Bordeaux:

ancillary biologic study; fibrinolysis; tranexamic acid; post-partum haemorrhage

Additional relevant MeSH terms:

Postpartum Hemorrhage; Hemorrhage; Pathologic Processes; Obstetric Labor Complications; Pregnancy Complications; Puerperal Disorders; Uterine Hemorrhage; Hemostatics; Coagulants