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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Arthropathy of Hip
• Intervention / Treatment: Drug: Placebo; Drug: Group 1: perfusion of 300 mg Exacyl; Drug: Group 2: perfusion of 500 mg Exacyl; Drug: Group 3: perfusion of 1000 mg Exacyl; Drug: Group 4: perfusion of 3000 mg Exacyl

Detailed Description

This dose-response study is a randomized double blind study with five groups of 30 patients each. Patients will be randomized to placebo, tranexamic acid (TXA) 300 mg, tranexamic acid (TXA) 500 mg, tranexamic acid (TXA) 1000 mg or tranexamic acid (TXA) 3000 mg. 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 Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Julien LANOISELEE, MD; Phone Number: +33 (0)477828554; Email: julien.lanoiselee@chu-st-etienne.fr
• Study Contact Backup: Name: Béatrice DEYGAS, CRA; Phone Number: +33 (0)477127655; Email: beatrice.deygas@chu-st-etienne.fr

Study Locations

• France
  • Saint-Étienne, France
    • Recruiting
    • Chu Saint-Etienne
    • Principal Investigator: Julien LANOISELEE, MD
    • Sub-Investigator: Jean-Yves BIEN, MD
    • Sub-Investigator: Pierre LAMBERT, MD
    • Sub-Investigator: Paul-Jacques ZUFFEREY, MD
    • Sub-Investigator: Maroua BECHA-OUESLATI, MD
    • Sub-Investigator: Jordan BONSIGNORE, MD
    • Sub-Investigator: Norbert TAMISIER, MD
    • Sub-Investigator: Zeina PRADES EL KHOURY, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient requiring primary hip arthroplasty (less than 3 months)
• Informed Consent from the patient or their legally authorized representative
• Affiliation to French Social Security Healthcare system

Exclusion Criteria:

• Hip fracture of less than 3 months
• Bilateral hip arthroplasty or anterior approach to hip arthroplasty
• Haemorrhagic surgery in the previous 2 weeks
• Contraindication to tranexamic acid
• Contraindication to apixaban
• Chronic use of anticoagulant
• Pregnancy
• Previous participation to this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Patient will be included in this group by randomization and they will receive an intravenous perfusion of NaCl (sodium chloride 9%; placebo) intravenous over 9 minutes, starting at the time of surgical incision.	Drug: Placebo; Patient will receive an intravenous perfusion of NaCl (sodium chloride 9%; placebo) intravenous over 9 minutes, starting at the time of surgical incision.
Experimental: Group 1: perfusion of 300 mg Exacyl; Patient will be included in the group 2 by randomization and they will receive an intravenous perfusion of 300 mg Exacyl (tranexamic acid) intravenous (IV) over 9 minutes, starting at the time of surgical incision.	Drug: Group 1: perfusion of 300 mg Exacyl; Patient will receive an intravenous perfusion of 300 mg Exacyl (tranexamic acid) intravenous (IV) over 9 minutes, starting at the time of surgical incision.
Experimental: Group 2: perfusion of 500 mg Exacyl; Patient will be included in the group 2 by randomization and they will receive an intravenous perfusion of 500 mg Exacyl (tranexamic acid) intravenous (IV) over 9 minutes, starting at the time of surgical incision..	Drug: Group 2: perfusion of 500 mg Exacyl; Patient will receive an intravenous perfusion of 500 mg Exacyl (tranexamic acid) intravenous (IV) over 9 minutes, starting at the time of surgical incision.
Experimental: Group 3: perfusion of 1000 mg Exacyl; Patient will be included in the group 3 by randomization and they will receive an intravenous perfusion of 1000 mg Exacyl (tranexamic acid) intravenous (IV) over 9 minutes, starting at the time of surgical incision.	Drug: Group 3: perfusion of 1000 mg Exacyl; Patient will receive an intravenous perfusion of 1000 mg Exacyl (tranexamic acid) intravenous (IV) over 9 minutes, starting at the time of surgical incision.
Experimental: Group 4: perfusion of 3000 mg Exacyl; Patient will be included in the group 4 by randomization and they will receive an intravenous perfusion of 3000 mg Exacyl (tranexamic acid) intravenous (IV) over 9 minutes, starting at the time of surgical incision.	Drug: Group 4: perfusion of 3000 mg Exacyl; Patient will receive an intravenous perfusion of 3000 mg Exacyl (tranexamic acid) intravenous (IV) over 9 minutes, starting at the time of surgical incision.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
haemoglobin decrease in the perioperative period	Percentage of haemoglobin change in the perioperative period. It requires the sampling of haemoglobin just before surgery (Day 1) and on the eighth postoperative day	Day 1 to Day 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tranexamic acid pharmacokinetics	For tranexamic acid pharmacokinetics, the outcome measure is the sampling of tranexamic blood concentration.	Day 1
D-Dimer kinetics	For tranexamic acid pharmacodynamics, the outcome is the sampling of D-Dimer levels.	Day 1
allogenic red blood cell transfusion	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.	Day 1 to day 8
severe anaemia	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.	Day 1 to day 8
incidence of symptomatic thrombotic events and death	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.	Day 1 to day 8
occurrence of a seizure	The endpoint is a combined criteria endpoint involving either the clinical observation of a generalized tonic-clonic seizure or a partial seizure or an epilepsy confirmed by an electroencephalogram interpreted by a neurologist blinded to the patient's inclusion group.	Day 8

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Saint Etienne
• Investigators: Principal Investigator: Julien LANOISELEE, MD, Chu Saint-Etienne

Study record dates

Study Major Dates

• Study Start (Actual): December 7, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: December 31, 2018
• First Submitted That Met QC Criteria: January 29, 2019
• First Posted (Actual): January 30, 2019

Study Record Updates

• Last Update Posted (Estimated): February 7, 2024
• Last Update Submitted That Met QC Criteria: February 5, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: arthroplasty; hip; tranexamic acid (TXA); Exacyl
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Joint Diseases; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Antifibrinolytic Agents; Hemostatics; Coagulants; Tranexamic Acid
• Other Study ID Numbers: 18CH052; 2018-004552-37 (EudraCT Number); 2022-502532-38-01 (Other Identifier: CTIS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No