Marietta 2020.

Study name	Randomised controlled trial comparing high versus low LMWH dosages in hospitalised patients with severe COVID‐19 pneumonia and coagulopathy not requiring invasive mechanical ventilation
Starting date	1 June 2020
Contact information	Marco Marietta, MD Azienda Ospedaliero‐Universitaria di Modena, Italy 0594224640 ext +39 | marco.marietta@unimore.it
Methods	Multicentre, open‐label, investigator‐sponsored, 2‐arm, parallel‐assignment RCT
Participants	300 participants, 18‐80 years, female and male Inclusion criteria (all required) Positive SARS‐CoV‐2 diagnostic (on pharyngeal swab of deep airways material) Severe pneumonia defined by the presence of at least one of the following criteria: respiratory rate ≥ 25 breaths/min arterial oxygen saturation ≤ 93% at rest on ambient air PaO2/FiO2 ≤ 300 mmHg Coagulopathy, defined by the presence of at least one of the following criteria: D‐dimer > 4 times the ULN reference range sepsis‐induced coagulopathy score > 4 No need for invasive mechanical ventilation Exclusion criteria Invasive mechanical ventilation Thrombocytopenia (platelet count < 80.000 mm³) Coagulopathy: INR > 1.5, aPTT ratio > 1.4 Impaired renal function (eGFR calculated by CKD‐EPI creatinine equation < 30 mL/min) Known hypersensitivity to enoxaparin History of HIT Presence of active bleeding or a pathology susceptible of bleeding in presence of anticoagulation (e.g. recent haemorrhagic stroke, peptic ulcer, malignant cancer at high risk of haemorrhage, recent neurosurgery or ophthalmic surgery, vascular aneurysms, arteriovenous malformations) Concomitant anticoagulant treatment for other indications (e.g. atrial fibrillation, VTE, prosthetic heart valves) Concomitant double antiplatelet therapy Administration of therapeutic doses of LMWH, fondaparinux, or UFH for > 72 h before randomisation; prophylactic doses are allowed Pregnancy or breastfeeding or positive pregnancy test Presence of other severe diseases impairing life expectancy (e.g. patients are not expected to survive 28 days given their pre‐existing medical condition) Lack or withdrawal of informed consent
Interventions	Experimental: high‐dose LMWH: 70 IU/kg twice daily, other name: Inhixa Comparator: low‐dose LMWH: enoxaparin 4000 IU daily
Outcomes	Primary Clinical worsening, defined as the occurrence of at least 1 of the following events, whichever comes first: (time frame: through study completion, up to 30 days) Death Acute myocardial infarction Objectively confirmed, symptomatic arterial or VTE Need for either non‐invasive ‐ CPAP or NIV ‐ or invasive mechanical ventilation for participants, who are in standard oxygen therapy by delivery interfaces at randomisation Need for invasive mechanical ventilation for participants, who are in non‐invasive mechanical ventilation at randomisation Secondary Any of the following events occurring within the hospital stay (time frame: through study completion, up to 30 days) Death Acute myocardial infarction Objectively confirmed, symptomatic arterial or VTE Need for either non‐invasive ‐ CPAP or NIV ‐ or invasive mechanical ventilation for participants, who are in standard oxygen therapy by delivery interfaces at randomisation Need for invasive mechanical ventilation for participants, who are in non‐invasive mechanical ventilation at randomisation Improvement of laboratory parameters of disease severity, including: D‐dimer level, plasma fibrinogen levels, mean platelet volume, lymphocyte/neutrophil ratio, IL‐6 plasma levels Mortality at 30 days (time frame: 30 days). Information about participants' status will be sought in those who are discharged before 30 days on day 30 from randomisation
Notes	NCT04408235 | EudraCT 2020‐001972‐13 | No data provided