NCT04367831.

Study name	Intermediate or prophylactic‐dose anticoagulation for venous or arterial thromboembolism in severe COVID‐19: a cluster based randomized selection trial (IMPROVE‐COVID)
Starting date	2 May 2020
Contact information	Sahil A. Parikh Columbia University, New York, New York, USA 212‐305‐7060 | sap2196@cumc.columbia.edu
Methods	Prospective, single‐centre, single‐blinded (outcomes assessor), 2‐armed, parallel‐assignment, cluster‐RCT
Participants	100 participants, ≥ 18 years, female and male Inclusion criteria Confirmed diagnosis of COVID‐19 by RT‐PCR New admission to eligible ICUs within 5 days. Transfer from non‐participating to participating ICU is eligible if otherwise meets eligibility criteria. Patients transferred between participating ICUs will maintain initial treatment assignment. Patients not on therapeutic anticoagulation and who were already admitted to participating ICU within 5 days of trial initiation are additionally eligible. Exclusion criteria Weight < 50 kg Contraindication to anticoagulation in the opinion of the treating clinician including overt bleeding platelet count < 50,000; BARC major bleeding in the past 30 days; GI bleeding within 3 months; history of intracranial haemorrhage; ischemics stroke within the past 2 weeks; craniotomy/major neurosurgery within the past 30 days; cardiothoracic surgery within the past 30 days; intra‐abdominal surgery within 30 days prior to enrolment; head or spinal trauma in the last months; history of uncorrected cerebral aneurysm or arteriovenous malformation (AVM); intracranial malignancy; presence of an epidural or spinal catheter; recent major surgery within the last 14 days; decrease in haemoglobin > 3 g/dL over the last 24 h; allergic reaction to anticoagulants (e.g. HIT) as documented in the electronic health records; ECMO support or other mechanical circulatory support Severe chronic liver dysfunction (history of portosystemic hypertension (HTN), oesophageal varices, or ≥ Child‐Pugh class C or similar; Model For End‐Stage Liver Disease (MELD) scores), abnormality in liver function tests (AST, ALT, bilirubin) 5 times > ULN A history of congenital bleeding diatheses or anatomical anomaly that predisposes to haemorrhage (e.g. haemophilia, hereditary hemorrhagic telangiectasia) Treating physician preference for therapeutic anticoagulation Enrolment in other concurrent studies related to anticoagulant or antiplatelet therapy Existing treatment with therapeutic anticoagulation during the previous 7 days of hospitalisation prior to ICU admission (e.g. for VTE, atrial fibrillation, mechanical valve, etc). Do‐not‐resuscitate (DNR)/do‐not‐intubate (DNI) or comfort measures only (CMO) orders prior to randomisation
Interventions	Experimental: intermediate‐dose anticoagulation UFH infusion at 10 units/kg/h with goal anti‐Xa 0.1 ‐0.3U/mL If estimated GFR ≥ 30 mL/min: enoxaparin 1 mg/kg SC daily Comparator: enoxaparin prophylactic dose following local guideline If estimated GFR ≥ 30 mL/min (stable kidney function): BMI < 40 kg/m²: enoxaparin 40 mg SC daily BMI 40‐50 kg/m²: enoxaparin 40 mg SC every 12 h BMI > 50 kg/m²: enoxaparin 60 mg SC every 12 h UFH at 5000‐7500 units SC every 8 h
Outcomes	Primary Total number of participants with clinically relevant venous or arterial thrombotic events in ICU (time frame: discharge from ICU or 30 days). Composite of being alive and without clinically‐relevant venous or arterial thrombotic events at discharge from ICU (without transfer to another ICU or palliative care unit/hospice) or at 30 days (if ICU duration lasted 30 days or longer) Secondary Total number of participants with in‐hospital clinically relevant venous or arterial thrombotic events (time frame: discharge from hospital or 30 days). Composite of being alive and without clinically‐relevant venous or arterial thrombotic events at discharge from ICU (without transfer to another ICU or palliative care unit/hospice) or at 30 days (if ICU duration lasted 30 days or longer) ICU length of stay (time frame: discharge from ICU or 30 days). Length of stay measured in days Total number of participants with the need for renal replacement therapy in the ICU (time frame: discharge from hospital or 30 days). The impact of intermediate‐dose anti‐coagulation compared with prophylactic anti‐coagulation on rates of AKI and renal recovery in the ICU will be measured with the total number of participants who need renal replacement therapy in the ICU Total number of participants with major bleeding in the ICU (time frame: discharge from hospital or 30 days). Major bleeding will be assessed by BARC criteria, also explored by ISTH and Thrombolysis in Myocardial Infarction (TIMI) criteria Hospital length of stay (time frame: discharge from hospital or 30 days). Length of stay measured in days
Notes	NCT04367831 | No data provided