Study of the Prognostic Value of the Coagulolytic Balance Dependent on Circulating Microvesicles in the Occurrence of Thrombotic Events After Total Knee Replacement in Orthopedic Surgery. (MOTiVE)

This is a prospective multicenter cohort study to evaluate the prognostic value of new biological markers in predicting thrombotic events after orthopedic surgery. According to the inclusion and non-inclusion criteria below, the study will include 387 major subjects who will undergo first-line total knee replacement and will receive the same standard prophylactic treatment: anticoagulation with Lovenox® (enoxaparin) 4000 IU/d subcutaneously 6 to 8 hours postoperatively and then daily for 15 days in combination with compression stockings.

Study Overview

• Status: Not yet recruiting
• Conditions: Knee Prosthesis
• Intervention / Treatment: Other: Thrombotic risk assessment

Detailed Description

Recruitment and follow-up of patients will be carried out in 3 hospitals by the respective orthopedic teams. Three hundred and eighty-seven patients will be included in the study, over a period of 36 months: 200 in Marseille, 100 in Nice and 87 in Nîmes.

The objective of the study was to evaluate the prognostic capacities of the coagulolytic balance of MVs measured after surgery at D0 in the occurrence of a symptomatic or asymptomatic venous thromboembolic event revealed by echodoppler at 1 month after total knee replacement surgery.

The management of the subjects is unchanged from the current recommendations and will be homogeneous between the three inclusion centers. Patients will be hospitalized for 5 days and will receive the usual prophylactic anticoagulant treatment with Lovenox® (enoxaparin sodium; LMWH) 4000 IU/d subcutaneously 6 to 8 hours postoperatively and then daily for 15 days in combination with compression stockings, which corresponds to the management of a PTG according to current recommendations.

• Study Type: Interventional
• Enrollment (Anticipated): 387
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Matthieu OLLIVIER; Phone Number: +33 04.91.74.50.12; Email: matthieu.ollivier@ap-hm.fr

Study Locations

• France
  • Bouches Du Rhône
    • Marseille, Bouches Du Rhône, France, 13354
      • Assistance Publique Hopitaux de Marseille

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subject, male or female, aged 18 to 85 years (upper age limit classically used in the literature of PTG79-81)
• First-line TKP (knee native to any prosthesis) performed to treat primary or secondary osteoarthritis.

In case of contralateral PTG, a delay of 12 months between the 2 prostheses will be respected according to the habits of the inclusion centers.

• ASA score <4 (American Society of Anesthesiologists)
• No contraindication to prophylactic treatment with low molecular weight heparin (LMWH)
• Subject not taking anticoagulant or antiaggregant therapy at therapeutic dose
• Subject who has signed the informed consent form
• Subject affiliated to the social security system

Exclusion Criteria:

• Subjects with a history of sepsis, tumor or trauma in the considered joint
• Subject with sepsis or acute infection
• Immunocompromised subject (HIV, transplant, chemotherapy, leukemia, glucocorticoids >3 months)
• Subjects with severe respiratory, circulatory or cardiac pathologies involving anticoagulant treatment likely to influence the coagulolytic balance.
• Subject with severe renal insufficiency (creatinine clearance < 30ml/min)
• Subject refusing to participate in the study or not signing the informed consent or unable to adhere to the study procedures
• Subjects who are minors, pregnant or breastfeeding, not affiliated with the social security system, or deprived of liberty
• Subject already included in an interventional trial (which may alter the results of that study)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Knee prosthesis group	Other: Thrombotic risk assessment; Collection of symptomatic thrombotic events occurring during the 5 days of hospitalization and then by telephone interview at M1 +/- 3 days. Complete echodoppler (proximal and distal) performed at M1 to highlight asymptomatic thrombotic events.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the Receiver Operating Characteristic curve	To assess the prognostic value of the microvesicle-dependent coagulolytic balance measured after D0 surgery (pre-administration of prophylactic treatment) in the occurrence of a post-total knee replacement thrombotic event (distal or proximal).	After surgery at Day 0

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best prognostic threshold of MV coagulolytic balance measured	Maximize sensitivity and specificity (Youden's method), and intrinsic and extrinsic performances associated with the threshold: sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, positive predictive value, negative predictive value, with their 95% confidence intervals.	After surgery at Day 0
Estimation of the area under the ROC curve with its 95% confidence interval - The procoagulant activity of MV is dependent on FT	To assess the overall prognostic value of FT-dependent MV procoagulant activity at D0 (pre- and post-surgery) and D3, for the occurrence of a symptomatic or asymptomatic thrombotic event at 1 month post-PTG, the best prognostic threshold, and the intrinsic and extrinsic performance associated with the determined threshold, together with their 95% confidence intervals	Day 0, Day 3 and 1 month post-PTG
Estimation of the area under the ROC curve with its 95% confidence interval - Fibrinolytic activity of MV	Allows assessment of the overall prognostic value of MV fibrinolytic activity at D0 (pre- and post-surgery) and D3, for the occurrence of a symptomatic or asymptomatic thrombotic event at 1 month post-PTG, best prognostic threshold, and intrinsic and extrinsic performance associated with the determined threshold, together with their 95% confidence interval.	Day 0, Day 3 and 1 month post-PTG
Estimation of the area under the ROC curve with its 95% confidence interval - Coagulolytic balance of MV	Allows assessment of the prognostic value of the coagulolytic balance of MVs at D0 (before and after surgery) and D3, for the occurrence of a symptomatic thrombotic event (pulmonary embolism or DVT) at 1 month post-PTG, the best prognostic threshold, and the intrinsic and extrinsic performances associated with the determined threshold, together with their 95% confidence interval	Day 0, Day 3 and 1 month post-PTG

Collaborators and Investigators

• Sponsor: Assistance Publique Hopitaux De Marseille
• Investigators: Study Director: François CREMIEUX, Assistance Publique Hopitaux de Marseille; Principal Investigator: Matthieu OLLIVIER, Assistance Publique Hopitaux de Marseille

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2023
• Primary Completion (Anticipated): June 1, 2026
• Study Completion (Anticipated): December 1, 2026

Study Registration Dates

• First Submitted: May 19, 2022
• First Submitted That Met QC Criteria: May 19, 2022
• First Posted (Actual): May 24, 2022

Study Record Updates

• Last Update Posted (Actual): April 21, 2023
• Last Update Submitted That Met QC Criteria: April 20, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: 2022-A00582-41

Drug and device information, study documents

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