PRADO: A Dose-response Study of Tranexamic Acid in Total Hip Arthroplasty

Sponsor

Centre Hospitalier Universitaire de Saint Etienne (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT03822793

Collaborator

(none)

250

Enrollment

Location

Arms

9.3

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A single preoperative dose of tranexamic acid (TXA) reduces blood loss and red blood cell transfusion in primary hip arthroplasty. Numerous regimens have been tested, ranging from 10mg/kg up to 3g. However the optimal dose to administer is unknown.

Condition or Disease	Intervention/Treatment	Phase
Arthropathy of Hip	Drug: Placebo Drug: Group 1: perfusion of 500 mg Exacyl Drug: Group 2: perfusion of 1000 mg Exacyl Drug: Group 3: perfusion of 1500 mg Exacyl Drug: Group 4: perfusion of 3000 mg Exacyl	Phase 2

Detailed Description

This dose-response study is a randomized double blind study with five groups of 50 patients each. Patients will be randomized to placebo, tranexamic acid (TXA) 500 mg, tranexamic acid (TXA) 1000 mg, tranexamic acid (TXA) 1500 mg or tranexamic acid (TXA) 3000mg. In addition a pharmacokinetic/pharmacodynamic study will be performed to identify the contribution of tranexamic acid (TXA) plasma concentration as a predictor of intra and postoperative D-Dimer values.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

250 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Masking Description:

randomized double blind study

Primary Purpose:

Treatment

Official Title:

Dose Study of Tranexamic Acid in Total Hip Replacement to Reduce Post-operative Hemoglobin Loss: A Phase 2 Randomized Double-blind Monocentric Study

Anticipated Study Start Date :

Sep 1, 2022

Anticipated Primary Completion Date :

May 31, 2023

Anticipated Study Completion Date :

Jun 10, 2023

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Patient will be included in this group by randomization and they will receive a perfusion of NaCl (sodium chloride 9%; placebo) intravenous over 10 minutes just before surgery.	Drug: Placebo Patient will receive a perfusion of NaCl (sodium chloride 9%; placebo) intravenous over 10 minutes just before surgery.
Experimental: Group 1: perfusion of 500 mg Exacyl Patient will be included in the group 2 by randomization and they will receive a perfusion of 500mg Exacyl (tranexamic acid) intravenous (IV) over 10 minutes just before surgery.	Drug: Group 1: perfusion of 500 mg Exacyl Patient will receive a perfusion of 500mg Exacyl (tranexamic acid) intravenous (IV) over 10 minutes just before surgery.
Experimental: Group 2: perfusion of 1000 mg Exacyl Patient will be included in the group 2 by randomization and they will receive a perfusion of 1000 mg Exacyl (tranexamic acid) intravenous (IV) over 10 minutes just before surgery.	Drug: Group 2: perfusion of 1000 mg Exacyl Patient will receive a perfusion of 1000mg Exacyl (tranexamic acid) intravenous (IV) over 10 minutes just before surgery.
Experimental: Group 3: perfusion of 1500 mg Exacyl Patient will be included in the group 3 by randomization and they will receive a perfusion of 1500 mg Exacyl (tranexamic acid) intravenous (IV) over 10 minutes just before surgery.	Drug: Group 3: perfusion of 1500 mg Exacyl Patient will receive a perfusion of 1500mg Exacyl (tranexamic acid) intravenous (IV) over 10 minutes just before surgery.
Experimental: Group 4: perfusion of 3000 mg Exacyl Patient will be included in the group 4 by randomization and they will receive a perfusion of 3000mg Exacyl (tranexamic acid) intravenous (IV) over 10 minutes just before surgery.	Drug: Group 4: perfusion of 3000 mg Exacyl Patient will receive a perfusion of 3000mg Exacyl (tranexamic acid) intravenous (IV) over 10 minutes just before surgery.

Outcome Measures

Primary Outcome Measures

haemoglobin decrease in the perioperative period [Day 8]
Percentage of haemoglobin change in the perioperative period. It requires the sampling of haemoglobin before surgery and on the eighth postoperative day.

Secondary Outcome Measures

Evolution of the concentration of tranexamic acid [Day 8]
For tranexamic acid pharmacokinetics, the outcome measure is the sampling of tranexamic blood concentration.
Evolution of the concentration of D-Dimer [Day 8]
For tranexamic acid pharmacodynamics, the outcome is the sampling of D-Dimer levels.
allogenic red blood cell transfusion [Day 8]
For allogenic red blood cell transfusion, the outcome measure will be the percentage of patients that will receive the transfusion of at least one allogenic red blood cell unit in the perioperative period.
severe anaemia [Day 8]
For severe anaemia (defined as a level of haemoglobin <10 gram by deciliter), the outcome measure will be the percentage of patients that will have at least one value of haemoglobin <10 gram by deciliter in the perioperative period.
incidence of symptomatic thrombotic events and death [Day 8]
For the incidence of symptomatic thrombotic events and death, the outcome measure is a combined criteria of venous events (deep venous thrombosis or pulmonary embolism), arterial events (acute coronary syndrome, stroke or peripheral arterial thrombosis) and death.
occurrence of a seizure [Day 8]
Upon the occurrence of a seizure, the endpoint is a clinical endpoint involving either the observation of a generalized tonic-clonic seizure or a partial seizure or absence with epilepsy confirmed by an electroencephalogram interpreted by a blind neurologist in the patient's inclusion group.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patient requiring primary hip arthroplasty (less than 3 months)
Consent of the patient or a family member or the support person

Exclusion Criteria:

Contraindication to tranexamic acid
Contraindication to apixaban
Pregnancy
Patient receiving a curative anticoagulating treatment in the preoperative period
Bilateral or previous hip arthroplasty
Hemorrhagic surgery less than 2 weeks old