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: the ProApix Study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Saint Etienne

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04], Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

24 Jun 2025 → ongoing

Decision date (initial)

2024-11-06

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-515329-27-00

ClinicalTrials.gov

NCT06474182

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic

To compare the pharmacodynamic effect of Apixaban measured by thrombin generation by thrombinography at peak concentration following a 2.5mg dose in patients treated for de novo multiple myeloma (i.e. chemotherapy naïve) (group 1) and in patients operated on for PTG (group 2) in a peripheral venous blood sample taken 2h (32) after Apixaban (H2).

Secondary objectives 4

1. To compare the pharmacokinetics by mass spectrometry of Apixaban in the two groups
2. To compare, in the two groups, the evolution of pharmacodynamics studied by thrombin generation (thrombinography) in the presence and absence of thrombomodulin.
3. Modelling the pharmacokinetic-pharmacodynamic relationship in the two groups.
4. To know the evolution of exposure to Apixaban in patients with MM at a distance from initial management in order to assess the impact of concomitant treatments and the response to treatment of MM (sampling at the 5th cycle of chemotherapy +/- 1 cycle) (criteria of variability specific to MM patients).

Conditions and MedDRA coding

Thromboembolism prophylaxis

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Patient over 18 years of age.
2. Signed informed consent.
3. Patient covered by a social security scheme.
4. Group 1 (MM): Patient suffering from de novo multiple myeloma for whom treatment including thromboprophylaxis with apixaban is recommended.
5. Group 2 (PTG): Patient undergoing knee joint replacement with a total prosthesis for whom thromboprophylaxis with apixaban is recommended.

Exclusion criteria 5

1. Indication for curative anticoagulant treatment.
2. Contraindication to the use of apixaban.
3. Pregnant or breast-feeding woman.
4. Refusal to sign the consent form.
5. Protected adult patient.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is the endogenous thrombin potential (ETP) measured by thrombinography using the MidiCAT method at peak concentration after administration of a 2.5mg dose in patients treated for de novo multiple myeloma (group 1) or operated on for total knee replacement (group 2) with a sample taken 2 hours after the first dose of ‘Apixaban’. ETP is expressed as the concentration of active thrombin multiplied by time (nM.min).

Secondary endpoints 4

1. Measurement of Apixaban concentration (in ng/mL) by mass spectrometry during the 12 hours following administration of a dose of Apixaban 2.5mg in both groups.
2. Evaluation of the pharmacodynamic evolution kinetics of thrombin generation (using the parameters ETP (nM/min), Lagtime (min), Time to peak (min), Thrombin peak (M Thrombin) in the presence and absence of thrombomodulin in both groups at H0, H2, H6 and H12 of Apixaban administration using the MidiCAT method.
3. Modelling of the pharmacokinetic-pharmacodynamic relationship in each group.
4. Evaluation of changes in pharmacokinetics (Apixaban dosage in ng/mL) and pharmacodynamics (thrombin generation using the MidiCAT method) after 5 cycles of chemotherapy +/- 1 cycle for patients in group 1.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Saint Etienne

Sponsor organisation

Centre Hospitalier Universitaire De Saint Etienne

Address

Avenue Albert Raimond

City

Saint Priest En Jarez

Postcode

42270

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Saint Etienne

Contact name

project manager

Public contact point

Organisation

Centre Hospitalier Universitaire De Saint Etienne

Contact name

project manager

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications