Venous Thromboembolism in Renally Impaired Patients and Direct Oral Anticoagulants

• Status: Recruiting
• Trial end date: 2022-06-01
• Target enrollment: 0
• Participant gender: All

Summary

In renally impaired patients with acute venous thromboembolism (VTE), standard-of-care (SOC) anticoagulation, i.e. heparins-vitamin K antagonists (VKA), at therapeutic dosage is associated with an increased risk of thromboembolic and bleeding complications compared to patients with normal renal function. Direct oral anticoagulants (DOAs) have been shown to be at least as effective and safe as SOC in VTE treatment. But in the clinical trials, moderate renally impaired patients were poorly represented and patients with severe renal insufficiency not at all. So no dose reduction was considered.

Surprisingly, DOAs have been approved for VTE treatment in moderate and severe renally impaired patients. There is need to evaluate a reduced dose of DOAs for VTE treatment in patients with moderate and severe renal insufficiency.

We plan to evaluate reduced doses of 2 DOAs (apixaban, rivaroxaban) compared to SOC in VTE patients with moderate or severe renal insufficiency in terms of net clinical benefit (recurrent VTE and major bleeding) at 3 months.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Centre Hospitalier Universitaire de Saint Etienne
• Collaborator: Ministry of Health, France
• Treatments: Anticoagulants; Apixaban; Calcium heparin; Heparin; Rivaroxaban; Vitamin K

Criteria

Inclusion Criteria:

• Patients with a moderate renal insufficiency defined by a creatinine clearance between 30 to 50 ml/min (Cockcroft and Gault formulae) or a severe renal insufficiency (between 15 to 29 ml/min)

• Patients with acute objectively confirmed symptomatic proximal deep-vein thrombosis (DVT) or pulmonary embolism (PE) (with or without deep-vein thrombosis), planned to be treated for at least 3 months

• Patients >18 years

• Life expectancy more than 3 months

• Social security affiliation

• Signed informed consent

Exclusion Criteria:

• Indication for anticoagulants other than VTE

• Active bleeding or a high risk of bleeding contraindicating anticoagulant treatment; a systolic blood pressure of more than 180 mm Hg or a diastolic blood pressure of more than 110 mm Hg

• Anticoagulation for more than 72 hours prior to randomization

• Chronic liver disease or chronic hepatitis

• Patient at high risk of bleeding

• Creatinine clearance <15 ml/min or end stage renal disease or indication for extra-renal dialysis

• Need for concomitant anti-platelet therapy other than aspirin 75-325 mg per day. However concomitant treatment with aspirin is discouraged in this population at bleeding risk.

• Concomitant use of a strong inhibitor of cytochrome P-450 3A4 (CYP3A4) (e.g., a protease inhibitor for human immunodeficiency virus infection or azole-antimycotics agents ketoconazole, itraconazole, voriconazole, posaconazole) or a CYP3A4 inducer (e.g., rifampin, carbamazepine, or phenytoin),

• Active pregnancy or expected pregnancy or no effective contraception

• Any contraindication listed in the local labeling of UFH, LMWH or VKA or oral anticoagulant.

• Cancer-associated VTE requiring long-term treatment with LMWH

• Life expectancy of less than 3 months.