NCT04520620

Concentration-effect Relationship of Enoxaparin for Thromboembolic Prevention

Evaluation of the Concentration-effect Relationship of Enoxaparin for Thromboembolic Prevention in COVID-19 Intensive Unit Care Patients.

• Status: Withdrawn
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Centre Hospitalier Universitaire de Saint Etienne · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Patients with COVID-19 have special demographic characteristics including thromboembolic risk factors . The pharmacokinetics of enoxaparin administered subcutaneously in the intensive care unit patient are not described. Finally, given the lack of knowledge on the pharmacokinetic/pharmacodynamic properties of enoxaparin in intensive care unit patients infected with SARS-CoV-2, we propose to conduct a prospective multicenter cohort study to collect the biological data necessary for its study.

Detailed description

D-dimers greater than 1 μg/mL are a prognostic factor for 28-day mortality (odds ratio=18, 2-128). The use of preventive doses of enoxaparin (4,000 to 6,000 anti-Xa per day) or unfractionated heparin (10,000 to 15,000 IU per day) has been associated with a reduction in mortality of approximately one-third in patients with D-dimer levels greater than 3 μg/mL or those with sepsis-induced coagulopathy (SIC (sepsis-induced coagulopathy) score \> 4) For the intensive care unit patient, the preventive enoxaparin dosages were increased to 4,000 anti-Xa IU twice daily and to 6,000 anti-Xa IU twice daily if the patient weighs more than 120 kg. Curative treatment is even proposed in cases of marked inflammatory syndrome and/or hypercoagulability (e.g. fibrinogen \> 8 g/L or D-Dimer \> 3 μg/mL or 3000 ng/mL) even without symptomatic thrombosis. Given the lack of data on the use of these high "prophylactic" doses of enoxaparin, it is proposed that anti-Xa activity be monitored after the 3rd injection, and then regularly in the event of renal failure (because LMWHs are renally eliminated), to look for overdosage exposing a higher risk of bleeding. It is also proposed to regularly monitor (at least every 48 hours) the hemostasis of patients in search of multivisceral failure, or of coagulopathy of consumption which will require a re-evaluation of the heparin therapy dosage, these events being associated with an increased risk of haemorrhage.

Conditions

• Sars-CoV2

Interventions

Type	Name	Description
DRUG	Lovenox 40 MG in 0.4 mL Prefilled Syringe	Patients with a high thrombotic risk: In patients with a BMI included between \< 30 kg/m² and \> 30 kg/m² without added thrombotic risk factor: * Enoxaparin 40 milligrams, (4,000 IU) twice daily subcutaneously (SC) for the entire duration of the intensive care hospitalization * if weight \> 120 kg, enoxaparin 60 milligrams (6000 IU) twice daily subcutaneously for the entire duration of the intensive care hospitalization Patients with a very high thrombotic risk: In patients with a BMI \> 30 kg/m2 with added thrombotic risk factor (active cancer, recent personal history of thromboembolic event), or if iterative or unusual catheter thromboses, or if marked inflammatory syndrome and/or hypercoagulability (e.g. fibrinogen \> 8 g/L or D-Dimer \> 3 μg/ml or 3000 ng/ml) \* Enoxaparin sodium curative at a dose of 100 IU/kg/12h subcutaneously (SC) not to exceed a dose of 100 mg/12 hours
DEVICE	Ultrasound of the lower limbs	A 4-point compression ultrasound will be performed. In case of suspicion, an angiologist will perform to check the absence of legs thrombosis.

Timeline

• Start date: 2020-05-02
• Primary completion: 2020-07-10
• Completion: 2020-07-10
• First posted: 2020-08-20
• Last updated: 2020-08-20

Locations

4 sites across 1 country: France