Comparison of the Effects of Apixaban on Thrombin Generation in Patients With de Novo Multiple Myeloma (ProApix)

Comparison of the Effects of Prophylactic Administration of Apixaban on Thrombin Generation in Patients With de Novo Multiple Myeloma and Patients Undergoing a Surgery for Total Knee Replacement

Patients with multiple myeloma (MM) are at high risk of venous thromboembolism (VTE) and these patients require adequate thromboprophylaxis. Following the publication of the AVERT clinical study, Apixaban is strongly recommended as a prophylactic treatment option for patients with cancer, based on high quality of evidence and a favorable efficacy/safety profile. A multicenter and ancillary study - APIXABOR - that measured the plasmatic concentration of Apixaban in patients with MM and treated with preventive dose has been conducted. The peak drug concentration was superior in MM plasma, as compared to non-myeloma patients under prophylaxis. Therefore, the present study evaluated whether differences in pharmacokinetics have an impact on pharmacodynamics (i.e. decrease in coagulability in MM patients as compared to non-MM patients undergoing a surgery for total knee replacement who also have VTE prophylaxis). In fine, this study may inform to better manage thromboprophylaxis in MM patients.

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma; Total Knee Replacement
• Intervention / Treatment: Procedure: Blood sampling; Drug: Apixaban

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Emilie CHALAYER, MD; Phone Number: 33 (0)477822814; Email: emilie.chalayer@chu-st-etienne.fr
• Study Contact Backup: Name: Florence RANCON; Phone Number: 33 (0)4 77 82 94 58; Email: florence.rancon@chu-st-etienne.fr

Study Locations

• France
  • Saint-Etienne, France, 42055
    • Recruiting
    • Chu de Saint-Etienne
    • Sub-Investigator: Julien LANOISELEE, MD
    • Sub-Investigator: Ludovic FOUILLET, MD
    • Sub-Investigator: Jean-Yves BIEN, MD
    • Sub-Investigator: Emmanuelle TAVERNIER, MD
    • Contact: Emilie CHALAYER, MD; Phone Number: 33 (0)4 77 82 28 14; Email: emilie.chalayer@chu-st-etienne.fr
    • Sub-Investigator: Jérôme CORNILLON, MD
    • Sub-Investigator: Charlotte DOUBLET, MD
    • Sub-Investigator: Tiphany NEEL, MD
    • Sub-Investigator: Manon SAPET, MD
    • Sub-Investigator: Hugo THEVENET, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years old,
• Signed informed consent,
• Patient covered by a social security scheme.
• Group 1 : patient with a diagnosis of de novo multiple myeloma, with an indication of thromboprophylaxis with Apixaban,
• Group 2 : patient requiring a surgery for total knee replacement, , with an indication of thromboprophylaxis with Apixaban.

Exclusion Criteria:

• Curative doses of anticoagulation treatment,
• Contra-indication to Apixaban,
• Pregnant or breastfeeding woman,
• Refusal to sign consent,
• Patient under legal protection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Blood sampling of patients with de novo multiple myeloma; Description: Blood sampling of patients with de novo multiple myeloma	Procedure: Blood sampling; Blood sampling; Drug: Apixaban; Treatment by Apixaban
Experimental: Blood sampling of patients undergoing total knee replacement; Description: Blood sampling of patients undergoing total knee replacement	Procedure: Blood sampling; Blood sampling; Drug: Apixaban; Treatment by Apixaban

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endogenous Thrombin potential (nM.min)	Endogenous Thrombin potential (nM.min) as measured with MidiCAT method at the concentration peak 2 hours after 2.5mg Apixaban treatment	2 hours after Apixaban Treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Apixaban concentration (ng/mL)	Apixaban concentration (ng/mL) as measured by mass spectrometry during 12 hours following Apixaban treatment (2.5mg) in both groups	Kinetics of 12 hours following Apixaban treatment in both groups
Pharmacodynamics' kinetics of Endogenous Thrombin Potential	MidiCAT method measure : Endogenous Thrombin Potential (nM.min)	Kinetics of 12 hours following Apixaban treatment in both groups
Pharmacodynamics' kinetics of Lagtime	MidiCAT method measure : Lagtime (min)	Kinetics of 12 hours following Apixaban treatment in both groups
Pharmacodynamics' kinetics of Time to peak	MidiCAT method measure : Time to peak (min)	Kinetics of 12 hours following Apixaban treatment in both groups
Pharmacodynamics' kinetics of Thrombin peak	MidiCAT method measure : Thrombin peak (M, Thrombin)	Kinetics of 12 hours following Apixaban treatment in both groups

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2025
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: April 23, 2024
• First Submitted That Met QC Criteria: June 19, 2024
• First Posted (Actual): June 25, 2024

Study Record Updates

• Last Update Posted (Estimated): September 25, 2025
• Last Update Submitted That Met QC Criteria: September 24, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Multiple myeloma; pharmacodynamics; thromboprophylaxis; coagulability
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Hemic and Lymphatic Diseases; Multiple Myeloma; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; apixaban; Blood Specimen Collection
• Other Study ID Numbers: 23CH293; ANSM (Other Identifier: 2025-A02220-49)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No