E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Confirmed diagnosis of SARS-CoV-2 with symptomatic COVID-19 infection |
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E.1.1.1 | Medical condition in easily understood language |
COVID-19 infection with symptoms and a positive test |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To demonstrate the superiority of prophylactic enoxaparin compared to the current standard of care (no enoxaparin) in reducing hospital admission and/or death within 21 days of randomisation in symptomatic individuals with COVID-19 in a community setting |
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E.2.2 | Secondary objectives of the trial |
• Evaluate the bleeding risk of prophylactic enoxaparin in symptomatic individuals with COVID-19 in a community setting compared to the current standard of care (no enoxaparin), within 21 days of randomisation. • Assess whether prophylactic enoxaparin reduces the number of individuals admitted to hospital requiring supplemental oxygen within 21 days of randomisation. • Assess whether prophylactic enoxaparin reduces the incidence of venous thromboembolism (deep vein thrombosis and/or pulmonary embolism) or ischemic stroke within 21 days of randomisation
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Signed Informed consent • Confirmed COVID-19 (i.e. symptoms + positive test for SARS-CoV-2) • Male or female, age ≥ 55 years • At least two of the following additional risk factors: o Age ≥ 70 years o Body mass index > 25 kg/m2 o Chronic obstructive pulmonary disease (COPD)* o Diabetes* o Cardiovascular disease* o Corticosteroid use *Defined as any disease requiring medical intervention or treatment.
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E.4 | Principal exclusion criteria |
• Contraindications to unfractionated heparin or LMWH • Recent (<48 hours) or planned spinal or epidural anesthesia or puncture, PCI or thrombolytic therapy within the preceding 24 hours • Increased risk for bleeding complications • Pregnant women • Severe renal impairment (GFR < 30 mL/min) • Receiving any antiplatelet therapy (with the exception of low dose (≤100mg) aspirin) or anticoagulant therapy (e.g. VKA, DOAC) • Patients participating in an interventional study that is outside the purview of TRI sponsored studies.
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E.5 End points |
E.5.1 | Primary end point(s) |
The composite of hospitalization or all-cause death within 21 days after randomization. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Death (at 21, 50 and 90 days) • All-cause • Cardiovascular • Non-Cardiovascular • Specific causes • Fatal bleed • Hospital admission (at 21, 50 and 90 days) o Pneumonia o Acute Respiratory distress syndrome o Acute medical care or admission to intensive care unit (ICU) o Mechanical ventilation/ Extracorporeal membrane oxygenation (ECMO) o Non-invasive ventilation/high flow oxygen o Hospitalized on supplemental oxygen o Hospitalized not requiring supplemental oxygen o Hospitalized not requiring ongoing medical care • Bleeding (as defined by ISTH criteria [12, 13]) (at 21 and 50 days) o Frequency o Location o Treatment (transfusion and units of blood products transfused) o Severity (classified as major, clinically relevant non-major and minor • Diagnosis of VTE: Deep Vein Thrombosis (DVT) or Pulmonary Embolism (PE) (at 21, 50 and 90 days)
• Diagnosis of Ischemic stroke (at 21, 50, and 90 days)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Death (at 21, 50 and 90 days) Bleeding (as defined by ISTH criteria [12, 13]) (at 21 and 50 days) Diagnosis of VTE: Deep Vein Thrombosis (DVT) or Pulmonary Embolism (PE) (at 21, 50 and 90 days) Diagnosis of Ischemic stroke (at 21, 50, and 90 days) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Standard of care treatment (No Enoxaparin) |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Belgium |
Brazil |
European Union |
India |
Russian Federation |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 6 |