Evaluation of the Minimum Concentration of Tranexamic Acid Required to Inhibit Fibrinolysis in a Population of Pregnant Women at Term.

January 18, 2018 updated by: Philippe VAN DER LINDEN, Brugmann University Hospital

Pregnancy induces a physiological change of hemostasis to a prothrombotic state : protein S decrease and increase of virtually all the clotting factors, in particular fibrinogen, von Willebrand factor and factor VIII. However, a state of hyperfibrinolysis may occur in the immediate postpartum period (especially after placental delivery), thereby promoting postpartum hemorrhage.

This state of hyperfibrinolysis is associated with the use of transfusions of blood products and the realization of hysterectomy.It is currently the most common etiology of maternal mortality in childbirth.There is an imperative to develop an efficient and reliable protocol for the management of this postpartum complication.

Tranexamic acid is an anti-fibrinolytic agent (like lysine) which acts by preventing the conversion of plasminogen to plasmin, by blocking the binding of plasminogen to the heavy chain of fibrin.The optimal dose of tranexamic acid enabling to inhibit fibrinolysis without increasing the complications rate remains to be defined. It is in this context that the investigators aim to evaluate, in an in-vitro model, the minimum dose of tranexamic acid required to inhibit fibrinolysis after activation of the latter by t-PA. The degree of fibrinolysis will be evaluated by thromboelastometry.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Pregnancy induces a physiological change of hemostasis to a prothrombotic state : protein S decrease and increase of virtually all the clotting factors, in particular fibrinogen, von Willebrand factor and factor VIII. However, a state of hyperfibrinolysis may occur in the immediate postpartum period (especially after placental delivery), thereby promoting postpartum hemorrhage.

This state of hyperfibrinolysis is associated with the use of transfusions of blood products and the realization of hysterectomy.It is currently the most common etiology of maternal mortality in childbirth. Although its incidence is low in western countries, it remains very high in the world.There is an imperative to develop an efficient and reliable protocol for the management of this postpartum complication.

Tranexamic acid is an anti-fibrinolytic agent (like lysine) which acts by preventing the conversion of plasminogen to plasmin, by blocking the binding of plasminogen to the heavy chain of fibrin.The use of this agent has spread in recent years in many types of surgery (cardiac, orthopedic, etc.), and in patient polytrauma. However, the number of studies evaluating its efficacy in the management (treatment and / or prevention) of postpartum hemorrhage is limited. In addition, the doses used are extrapolated from studies of a different population (multiple trauma, cardiac surgery, etc).

The tranexamic acid proposed scheme is currently used is not suitable for the population of pregnant women at term. It was established arbitrarily on the basis of the adult population without considering the physiological and metabolic characteristics of the term pregnancy. The optimal dose of tranexamic acid enabling inhibition of fibrinolysis, without increasing the complications rate, remains thus to be defined.

It is in this context that the investigators aim to evaluate, in an in-vitro model, the minimum dose of tranexamic acid required to inhibit fibrinolysis after activation of the latter by t-PA. The degree of fibrinolysis will be evaluated by thromboelastometry.

Study Type

Interventional

Enrollment (Actual)

40

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Brussels, Belgium, 1020
        • CHU Brugmann

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Female

Description

Inclusion Criteria:

Pregnant women group:

  • pregnant women at term (>37 weeks of gestation)
  • patients admitted for delivery or elective cesarian section
  • written informed consent

Healthy volunteers group:

- women aged from 18 to 40

Exclusion Criteria:

  • Dying patients (ASA 5)
  • Jehovah's witnesses
  • Patients with pre-eclampsia, HELLP syndrome, placenta previa or placental abruption.
  • Multiple pregnancy
  • Presence of preoperative coagulation disorders defined as: platelets <150,000 / mm3; PTT <70%; aPTT> 33 sec; fibrinogen <350 mg / dL.
  • Treatment with anticoagulant or antiplatelet agent.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: NON_RANDOMIZED
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Pregnant women at term, vaginal childbirth
Procedure: Blood sampling (pregnant)

5.4 ml of venous blood will be taken during the delivery or the caesarian procedure, in addition to the standard of care blood sampling.

This blood vial will be sent to the coagulation laboratory and all tests will be performed in vitro. The blood sample will be split in several aliquots. In each blood sample, fibrinolysis will be activated by the plasminogen tissular activator (tPA - concentration: 1066 UtPA/ml). Tranexamic acid will be added at increasing concentrations (2.5 microg/ml up to 40 microg/ml) to each sample and coagulation will be measured by two different tests: EXTEM and NATEM.
Experimental: Pregnant women at term, cesarean delivery
Procedure: Blood sampling (pregnant)

5.4 ml of venous blood will be taken during the delivery or the caesarian procedure, in addition to the standard of care blood sampling.

This blood vial will be sent to the coagulation laboratory and all tests will be performed in vitro. The blood sample will be split in several aliquots. In each blood sample, fibrinolysis will be activated by the plasminogen tissular activator (tPA - concentration: 1066 UtPA/ml). Tranexamic acid will be added at increasing concentrations (2.5 microg/ml up to 40 microg/ml) to each sample and coagulation will be measured by two different tests: EXTEM and NATEM.
Experimental: Female volunteers, age 18 to 40
Procedure: Blood sampling (non pregnant)

5.4 ml of venous blood will be taken.

This blood vial will be sent to the coagulation laboratory and all tests will be performed in vitro. The blood sample will be split in several aliquots. In each blood sample, fibrinolysis will be activated by the plasminogen tissular activator (tPA - concentration: 1066 UtPA/ml). Tranexamic acid will be added at increasing concentrations (2.5 microg/ml up to 40 microg/ml) to each sample and coagulation will be measured by two different tests: EXTEM and NATEM.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Coagulation (EXTEM)
Time Frame: within 24h of blood collection
Coagulation will be tested using the EXTEM test (test evaluating the extrinsic coagulation pathway after its activation by tissue factor)
within 24h of blood collection
Coagulation (NATEM)
Time Frame: within 24h of blood collection
Coagulation will be tested using the NATEM test (test evaluating coagulation after startem addition (for recalcification of citrated blood) and without activator addition)
within 24h of blood collection

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Brugmann University Hospital

Investigators

  • Principal Investigator: Arnaud Lechien, MD, CHU Brugmann

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2015

Primary Completion (Actual)

April 1, 2016

Study Completion (Actual)

April 1, 2016

Study Registration Dates

First Submitted

October 16, 2015

First Submitted That Met QC Criteria

October 16, 2015

First Posted (Estimate)

October 20, 2015

Study Record Updates

Last Update Posted (Actual)

January 19, 2018

Last Update Submitted That Met QC Criteria

January 18, 2018

Last Verified

January 1, 2018

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • CHUB-Fibrinolyse

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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