Apixaban for Autoimmune hemolytic anemia

Inclusion criteria

• {"criterion_text":"- Patient who provided free, written and informed consent"}
• {"criterion_text":"- Patient aged ≥ 18 years"}
• {"criterion_text":"- Patient with a diagnosis of primary or secondary autoimmune hemolytic anemia (AIHA) (infections, hematologic diseases, systemic diseases), according to the following criteria: - Hemoglobin <12 g/dL - and decreased haptoglobin (<0,4 g/L) - and positive direct antiglobulin test (direct Coombs test) (IgG +/- C3d)"}
• {"criterion_text":"- Newly diagnosed or relapsed patient (relapse is defined as a decrease in basal hemoglobin in association with AIHA - thus meeting the above criteria: Hb <12 g/dl and haptoglobin <0.4 g/L and IgG-positive TDA with or without C3d - and for whom the investigator deems it necessary to initiate etiological treatment specific to AIHA)"}
• {"criterion_text":"- Patient with an estimated life expectancy of more than 6 months"}

Exclusion criteria

• {"criterion_text":"- Patients with immediate symptomatic VTE, confirmed by appropriate complementary examinations (venous Doppler of the lower limbs, thoracic CT angiography or pulmonary scintigraphy)."}
• {"criterion_text":"- Patients with a contraindication to enoxaparin: - hypersensitivity to enoxaparin sodium, heparin or its derivatives, including other low-molecular-weight heparins (LMWH), or to any of the excipients, - history of heparin-induced thrombocytopenia"}
• {"criterion_text":"- Patient with cold agglutinin-related AIHA (C3d-positive ADT alone with identification of cold agglutinins)"}
• {"criterion_text":"- Patient with severe hemostasis disorders: - hypofibrinogenemia < 2 g/L, - disseminated intravascular coagulation (APTT prolongation >1.2, and PT <50%, and thrombocytopenia <100 G/L, and D-Dimer >500 μg/L) - hemophilia"}
• {"criterion_text":"- Patient whose clinical condition requires hospitalization in an intensive care unit"}
• {"criterion_text":"- Patient who has already participated in the study"}
• {"criterion_text":"- Patient not affiliated to national health insurance"}
• {"criterion_text":"- Patient under legal protection (curatorship, guardianship)"}
• {"criterion_text":"- Patient subject to a court order"}
• {"criterion_text":"- Pregnant, parturient or breastfeeding women"}
• {"criterion_text":"- Patient with physiological capacity to procreate (having had her first menstrual period and not menopausal and not presenting permanent sterility (hysterectomy, bilateral salpingectomy, bilateral oophorectomy)) and unable to have effective contraception (i.e., provided by an estrogenprogestin oral contraceptive or progestogen, a contraceptive implant, an intrauterine device or a tubal ligation)"}
• {"criterion_text":"- Patients on curative anticoagulation (VTE, atrial fibrillation)"}
• {"criterion_text":"- Patient of legal age who is unable to provide consent"}
• {"criterion_text":"- Patient on dual antiplatelet treatment"}
• {"criterion_text":"- Patient with active bleeding"}
• {"criterion_text":"- Patient with a known condition or lesion at risk of bleeding"}
• {"criterion_text":"- Patient with ischemic stroke with hemorrhagic transformation within 6 months prior to inclusion"}
• {"criterion_text":"- Patient on preventive anticoagulation for 14 days or more"}
• {"criterion_text":"- Patient with a contraindication to apixaban: - Known hypersensitivity to the molecule or to any of the excipients, - thrombocytopenia <100 G/L, - kidney failure (glomerular filtration rate < 30 ml/min/1.73m²), - Active liver disease (liver failure defined as Factor V <50% or INR >1.5, ALT elevation >2 times the upper limit of normal)"}
• {"criterion_text":"- Patients receiving concomitant treatment with potent CYP3A4 inducers (rifampicin, phenytoin, carbamazepine, phenobarbital, St. John's wort) or potent CYP3A4 inhibitors (azole antifungals, HIV protease inhibitors), if these treatments cannot be discontinued or modified."}

Primary endpoints

• {"endpoint_text":"- Occurrence of clinical venous thromboembolic events (deep vein thrombosis (DVT) and pulmonary embolism (PE)) within 24 weeks of randomization defined by the presence of DVT confirmed by venous Doppler and/or PE confirmed by thoracic CT angiography or ventilation/perfusion lung scintigraphy.","definition_or_measurement_approach":"Defined by presence of DVT confirmed by venous Doppler and/or PE confirmed by thoracic CT angiography or ventilation/perfusion lung scintigraphy, assessed within 24 weeks of randomization."}

Secondary endpoints

• {"endpoint_text":"- Time to onset of venous thromboembolic events within 24 weeks of AIHA diagnosis or relapse","definition_or_measurement_approach":"Time from diagnosis or relapse to confirmed VTE event within 24 weeks."}
• {"endpoint_text":"- Occurrence of AE and SAE:Occurrence of a major hemorrhagic event, defined by the ISTH as clinically significant acute bleeding associated with one or more of the following: decrease in hemoglobin level of more than 2 g/dL or transfusion of at least 2 packed red blood cells (provided transfusion is not justified by AIHA), hemorrhage at a critical site (cerebral, spinal cord, retroperitoneal, intraocular, muscular with compartment syndrome, pericardial) or resulting in death","definition_or_measurement_approach":"Major bleeding defined per ISTH criteria (Hb drop >2 g/dL, transfusion ≥2 units unless justified by AIHA, bleeding at critical sites, or fatal)."}
• {"endpoint_text":"- Occurrence of AE and SAE: Clinically significant non-major bleeding, defined as bleeding which does not meet the criteria for a major bleeding event, but which requires either medical attention or unscheduled medical contact (consultation or telephone), or which necessitates transient or permanent discontinuation of treatment, or which is responsible for discomfort or a reduction in the patient's quality of life.","definition_or_measurement_approach":"Bleeding not meeting major criteria but requiring medical attention or causing treatment discontinuation or reduced quality of life."}
• {"endpoint_text":"- Occurrence of AE and SAE: Minor bleeding defined as any bleeding that does not meet the criteria for major or clinically significant non-major bleeding.","definition_or_measurement_approach":"Any bleeding that does not meet criteria for major or clinically significant non-major bleeding."}
• {"endpoint_text":"- Occurrence of AE and SAE: Any major cardiovascular event, whether fatal or not","definition_or_measurement_approach":"Occurrence of major cardiovascular events (fatal or non-fatal); specific adjudication criteria not detailed in provided data."}
• {"endpoint_text":"- Occurrence of AE and SAE: Other adverse events: splanchnic venous thrombosis","definition_or_measurement_approach":"Occurrence of splanchnic venous thrombosis as an adverse event; diagnosis per standard imaging modalities."}
• {"endpoint_text":"- Occurrence of death","definition_or_measurement_approach":"All-cause mortality occurring during study follow-up."}
• {"endpoint_text":"- Determination of biological factors that may contribute to or be correlated with thromboembolic risk (D-dimer, sCD163, plasma hemoglobin, NETose, etc.)","definition_or_measurement_approach":"Laboratory measurement of specified biomarkers (D-dimer, sCD163, plasma hemoglobin, NETose, etc.) to assess correlation with thromboembolic risk."}

France

Earliest CTIS Part Ii Submission Date

26-03-2024

Latest Decision Or Authorization Date

15-12-2025

Processing Time Days

629

Number Of Sites

14

Number Of Participants

72

Primary sponsor

Full Name

Centre Hospitalier Universitaire De Dijon

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France