Clinical trial NCT04520620: Concentration-effect Relationship of Enoxaparin for Thromboembolic Prevention
Official title: Evaluation of the Concentration-effect Relationship of Enoxaparin for Thromboembolic Prevention in COVID-19 Intensive Unit Care Patients.
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Sars-CoV2
Keywords: enoxaparin
intensive care unit
pharmacokinetics
SARS-Co-V-2
Lovenox
Lead sponsor: Centre Hospitalier Universitaire de Saint Etienne
Sponsor class: OTHER
Collaborators: name: CHU Saint-Etienne - Laboratoire de Pharmacologie - Toxicologie - Gaz du sang
First posted: 2020-08-20
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: Inclusion Criteria:

* Aged \> 18 ans
* SARS-CoV-2 infected intensive care unit patients
* Diagnosis of SARS-CoV-2 respiratory infection was made with a nasopharyngeal swab or a deep respiratory specimen.
* Patient receiving enoxaparin treatment as part of care or as part of a clinical trial for the prevention or treatment of thromboembolic venous disease.
* Patient affiliated or entitled to a social security scheme

Exclusion Criteria:

* Creatinine clearance according to Cockcroft and Gault \<30ml/min.
* Hypersensitivity to enoxaparin sodium, heparin or its derivatives, including other low molecular weight heparins (LMWHs)
* History of immune-mediated heparin-induced thrombocytopenia (HIT) in the last 100 days or in the presence of circulating antibodies
* Active clinically significant bleeding or a condition associated with a high risk of bleeding, such as a recent hemorrhagic stroke, gastrointestinal ulcer, the presence of a malignant tumour at high risk of bleeding, recent brain, spinal or ophthalmologic surgery, known or suspected esophageal varices, arteriovenous malformations, vascular aneurysm or major intrarachidian or intracerebral vascular abnormalities.
* Spinal, epidural or locoregional anaesthesia or anaesthesia when enoxaparin sodium is used for curative treatment within the previous 24 hours

Primary outcomes:
measure: Measure of anti-Xa activity
timeFrame: Up to 1 month
Secondary outcomes:
measure: Analysis of hemorrhagic risk
timeFrame: Up to 1 month
measure: Venous thromboembolic events
timeFrame: Up to 1 month
measure: Analysis individual patient characteristics by the biomarker of Kidney function
timeFrame: Up to 1 month
measure: Analysis individual patient characteristics by the biomarker of inflammation
timeFrame: Up to 1 month
measure: Analysis individual patient characteristics by the biomarker of coagulation
timeFrame: Up to 1 month
measure: Demographic characteristics
timeFrame: Up to 1 month
Other outcomes:
Locations:
city: Montélimar
country: France
facility: Groupement Hospitalier des portes de Province
city: Roanne
country: France
facility: Centre Hospitalier de Roanne
city: Saint-Étienne
country: France
facility: CHU de Saint-Etienne
city: Saint-Étienne
country: France
facility: Clinique Mutualiste
Study officials:
affiliation: CHU SAINT-ETIENNE
name: Paul ZUFFEREY, MD
role: PRINCIPAL_INVESTIGATOR
References: