Concentration-effect Relationship of Enoxaparin for Thromboembolic Prevention (COV-ENOX)
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|ClinicalTrials.gov Identifier: NCT04520620|
Recruitment Status : Withdrawn (End of the COVID 19 epidemic in the region and decision to participate in a national study on the same subject (COVI-DOSE).)
First Posted : August 20, 2020
Last Update Posted : August 20, 2020
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.
|Condition or disease||Intervention/treatment||Phase|
|Sars-CoV2||Drug: Lovenox 40 MG in 0.4 mL Prefilled Syringe Device: Ultrasound of the lower limbs||Phase 4|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||0 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Evaluation of the Concentration-effect Relationship of Enoxaparin for Thromboembolic Prevention in COVID-19 Intensive Unit Care Patients.|
|Actual Study Start Date :||May 2, 2020|
|Actual Primary Completion Date :||July 10, 2020|
|Actual Study Completion Date :||July 10, 2020|
Experimental: enoxaparin treatment
Patients infected by SARS-CoV-2 in intensive care unit with enoxaparin treatment will be included.
They will have enoxaparin pharmacokinetic and ultrasound of the lower limbs at 7, 14 and 21 days after inclusion.
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:
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
Other Name: enoxaparin
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.
- Measure of anti-Xa activity [ Time Frame: Up to 1 month ]Measure of anti-Xa activity by chromogenic method.
- Analysis of hemorrhagic risk [ Time Frame: Up to 1 month ]
Hemorrhagic risk is composite of :
- Major haemorrhage as defined by the International Society on Thrombosis and Haemostasis (ISTH) definition
- clinically significant haemorrhage
- Venous thromboembolic events [ Time Frame: Up to 1 month ]
Venous thromboembolic events is composite of:
- symptomatic or symptomatic proximal deep vein thrombosis
- asymptomatic or symptomatic pulmonary embolism
- Analysis individual patient characteristics by the biomarker of Kidney function [ Time Frame: Up to 1 month ]Rate of creatinine.
- Analysis individual patient characteristics by the biomarker of inflammation [ Time Frame: Up to 1 month ]Biomarker of inflammation is composite of C-reactive protein (CRP) and inflammatory cytokines.
- Analysis individual patient characteristics by the biomarker of coagulation [ Time Frame: Up to 1 month ]Biomarker of coagulation is composite of fibrinogen and D-Dimers.
- Demographic characteristics [ Time Frame: Up to 1 month ]Analysis of weight, age, sex, height, presence of a high thrombotic risk factor (history of venous thrombotics, active cancer, invasive mechanical ventilation).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04520620
|Groupement Hospitalier des portes de Province|
|Centre Hospitalier de Roanne|
|CHU de Saint-Etienne|
|Principal Investigator:||Paul ZUFFEREY, MD||CHU SAINT-ETIENNE|