Efficacy of Prolonged Anticoagulation for Primary Prevention of Venous Thromboembolic Disease in Autoimmune Hemolytic Anemia: a Prospective, Phase II, Randomized, Multicenter Study

NCT05089227 | Recruiting Phase 2

• 1 other identifier: AUDIA PHRCI 2019
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

Autoimmune hemolytic anemia (AIHA) is a rare autoimmune disease (incidence \<1/100,000 population) responsible for the destruction of red blood cells by the host immune system, notably through the action of autoantibodies. Apart from complications related to anemia, the occurrence of venous thromboembolism (VTE) in this population is frequent, estimated at 20-27%. The risk of VTE is highest during the period of hemolysis, especially during the first 3 months after the diagnosis of AIHA. This risk is 7.5 \[4.7; 12.0\] times greater than in the general population. No clinical predictive factor for VTE was identified and the usual factors (cancer, previous VTE, bed rest \>3 days, surgery, age \>70 years, heart or respiratory failure, myocardial infarction, stroke, obesity, hormone replacement therapy) were not considered. Several biological risk factors have been suggested (depth of anemia, bilirubin level, leukocyte count, antiphospholipid antibodies) but have not been confirmed in other studies. AIHA is therefore a risk factor for VTE in its own right, and the National Diagnostic and Care Protocol (NDCP) recommends the implementation of VTE prevention during acute hemolysis (Grade C). However, the value of this prophylaxis has never been prospectively evaluated and its duration is empirical. In practice, low-molecular-weight heparin (LMWH) is generally used during "flare-ups" of AIHA (diagnosis and relapse) in hospitalized patients, but is rarely continued beyond the hospital phase when VTE also occurs in ambulatory patients. Thus, we hypothesize that prolonged preventive anticoagulation during the 12-week risk period following diagnosis or relapse of AIHA could decrease the incidence of VTE. In orthopedic surgery, this strategy has been proven to decrease VTE from 50% to 10-15%. In certain high-risk medical situations, prolonged prophylaxis with apixaban has been shown to decrease the occurrence of VTE from 10.2% to 4.2% in solid cancers4 and from 4-11% to 2% in myeloma.

Conditions

Prolonged Anticoagulation; Venous Thromboembolic Disease; Autoimmune Hemolytic Anemia

Outcome Measures

Primary Outcomes (1)

• Occurrence of clinical venous thromboembolic events (deep vein thrombosis (DVT) and pulmonary embolism (PE))

  defined by the presence of DVT confirmed by venous Doppler and/or PE confirmed by thoracic angioscan or ventilation/perfusion lung scintigraphy.

  24 weeks after randomization

Study Arms (2)

"intervention" group

EXPERIMENTAL

Drug: treatment "intervention"; Biological: biological assessment

"standard" group

ACTIVE COMPARATOR

Drug: treatment "standard"; Biological: biological assessment

Interventions

treatment "intervention" DRUG

for a total of 12 weeks, prophylactic heparin therapy during hospitalization followed by prophylactic oral anticoagulation with apixaban

"intervention" group

treatment "standard" DRUG

during hospitalization prophylactic heparin therapy followed by management without prophylactic anticoagulation.

"standard" group

biological assessment BIOLOGICAL

CBC, reticulocytes, haptoglobin, LDH, bilirubin

"intervention" group; "standard" group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient aged ≥ 18 years
• 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)
• Patient newly diagnosed or relapse
• Patient with an estimated life expectancy of more than 6 months
• Patient who provided free, written and informed consent

You may not qualify if:

• Patients with immediate symptomatic VTE, confirmed by appropriate complementary examinations (venous Doppler of the lower limbs, thoracic angioscanner or pulmonary scintigraphy).
• Patients on curative anticoagulation (venous thromboembolic disease, atrial fibrillation)
• Patient on dual antiaggregation treatment
• Patient with active bleeding
• Patient with a known condition or lesion at risk of bleeding
• Patient on preventive anticoagulation for 14 days or more
• 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)
• Patients receiving concomitant CYP3A4 inducers (rifampin, phenytoin, carbamazepine, phenobarbital, St. John's Wort) or CYP3A4 inhibitors (azole antifungals, HIV protease inhibitors), if these therapies cannot be discontinued or modified
• Patients with a contraindication to enoxaparin:
• allergy to the drug
• history of heparin-induced thrombocytopenia

Sponsors & Collaborators

• Centre Hospitalier Universitaire Dijon: lead

Study Sites (1)

Chu Dijon Bourgogne

Dijon, 21000, France

RECRUITING

MeSH Terms

Conditions

Anemia, Hemolytic, Autoimmune

Interventions

Crisis Intervention

Condition Hierarchy (Ancestors)

Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Psychotherapy; Behavioral Disciplines and Activities

Central Study Contacts

Sylvain AUDIA

CONTACT

03.80.29.34.32; sylvain.audia@chu-dijon.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 11, 2021
• First Posted: October 22, 2021
• Study Start: February 3, 2022
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2028
• Last Updated: December 22, 2025

Record last verified: 2025-12

Locations

FR (1)