A Phase 3 interventional study of Apixaban and Rivaroxaban in Renal Insufficiency, sponsored by Centre Hospitalier Universitaire de Saint Etienne. Terminated at 31 sites in France. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-10-19.
Sponsored by Centre Hospitalier Universitaire de Saint Etienne · Phase 3, Interventional, and Treatment
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.
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. These patients represent more than 20% of the VTE population in clinical practice. 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 (\<10%) and patients with severe renal insufficiency not at all. So no dose reduction was considered.
The new DOAs have also been developed for stroke prevention in atrial fibrillation (SPAF). Patients including in AF trials are generally older and more prone to present renal impairment (>20%) than in VTE trials. So a reduced dose of DOAs was evaluated and shown to be at least as effective as, and safer than VKA in the subgroup of patients with moderate renal insufficiency (creatinine clearance between 30 to 50 ml/min).
Surprisingly, DOAs have been approved for VTE treatment and SPAF in moderate and severe renally impaired patients (creatinine clearance between 15 to 30 mL/min). Moreover, patients have to receive a reduced dose of DOAs for SPAF but a full dose of DOAs for VTE that could be associated with an increased bleeding risk, as suggested by some subgroup analyses. So, there, there is need to evaluate a reduced dose of DOAs for VTE treatment in patients with moderate and severe renal insufficiency (creatinine clearance between 15 to 50 mL/min).
Apixaban and rivaroxaban appear to be the best candidates since:
Finally 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.
1,995 studies on the registry are indexed under Renal Insufficiency; 173 are open to participants now.
This study's enrollment of 203 is above the median of 43 across 1,504 interventional studies indexed under Renal Insufficiency.
Browse Renal Insufficiency studies →Centre Hospitalier Universitaire de Saint Etienne is the lead sponsor of 578 studies on the registry; 128 are open to participants now.
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Exclusion Criteria:
The experimental group receiving DOA regimens: patients will be secondarily randomly assigned within DOAs group between: * Apixaban (Eliquis® tablet) 10 mg bid for 7 days then 2.5 mg bid for 3 months * Rivaroxaban (Xarelto® tablet) 15 mg bid for 21 days then 15 mg od for 3 months.
Drug: Apixaban · Drug: Rivaroxaban
The control group receiving the standard of care (SOC), i.e. heparins/VKA regimen. Patients will receive the current recommended therapy: subcutaneous or intravenous UFH/VKA in case of severe renal insufficiency and subcutaneous LMWH/VKA in case of moderate renal insufficiency for at least 5 days. VKA will begin concomitantly and continue for 3 months.
Drug: Heparin · Drug: VKA
Direct Oral Anticoagulant
Also known as: Eliquis®
Direct Oral Anticoagulant
Also known as: Xarelto®
Standard Of Care
Standard Of Care
Also known as: vitamin K antagonists
Non inferiority of reduced doses of DOAs
To demonstrate that reduced doses of DOAs (rivaroxaban or apixaban) are non-inferior to standard of care (heparins/VKA) on the net clinical benefit (recurrent VTE and major bleeding) in renally impaired patients suffering from an acute VTE.
Time frame: Month 3
Bleeding events
To demonstrate the non--inferiority of reduced dose of DOAs on the risk of major bleedings.
Time frame: Month 3
Venous Thromboembolism (VTE) events
To demonstrate the non--inferiority of reduced dose of DOAs on the risk of recurrent VTE.
Time frame: Month 3
Plan to share: No
This study is terminated, as verified in Oct 2022. You cannot join it, but the record below documents what was studied.
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Centre Hospitalier Universitaire de Saint Etienne