Table 2 Ongoing registered clinical trials of thrombolytics for the management of COVID-19
From: Pharmacotherapy consideration of thrombolytic medications in COVID-19-associated ARDS
Thrombolytic | ID | Study type | Recruiting status | Numbers of patients | Population age (years) | Intervention group(s) | Primary outcomes | Secondary outcomes | References |
|---|---|---|---|---|---|---|---|---|---|
Alteplase | NCT04926428 | RCT | Completed | 15 | 18–80 | Alteplase | Changes in lung perfusion | Coagulation (changes in D-Dimer, standard coagulation test and fibrinogen), Oxygenation (changes in PaO2/FiO2) | [98] |
Nebulized Alteolase | NCT04356833 | RCT | Recruiting | 66 | 16–70 | Group 1: 10 mg rt-PA nebulized QID for 14 days, Group 2: 20 mg rt-PA in nebulized TDS for 14 days, Group 3:control | treatment efficacy, Change in PaO2/FiO2, Safety, fibrinogen levels | lung compliance, Clinical status, SOFA score, oxygen free days, ventilator-free days, ICU stay, incidence and duration of New oxygen via ventilation use, incidence and duration of MV, hospital mortality | [99] |
Alteplase | NCT04357730 | RCT | Not recruiting | 50 | 18–75 | Group 1: Alteplase 50 mg bolus (10 mg push, 40 mg over 2 h) Group 2: Alteplase 50 mg bolus plus drip (bolus of 10 mg push, 40 mg over 2 h), then a drip of 2 mg/h over 24 h (total 48 mg infusion) Group 3: control | PaO2/FiO2 improvement | PaO2/FiO2 ≥ 200 or 50% increase in PaO2/FiO2, NEWS2, NIAID ordinal scale, 48 h, 14 and 28 days in-hospital mortality, ICU-free days, coagulation-related event-free days, Ventilator-free days, Successful and weaning from paralysis extubation, Survival to discharge | [101] |
Alteplase | NCT04640194 | RCT | Recruiting | 270 | ≥ 18 years | Group 1: low dose of Alteplase plus SOC, Group 2: high dose of Alteplase plus SOC, Group 3: SOC | Time to clinical improvement or hospital discharge | All-cause mortality, ventilator-free days, Improvement of SOFA score, Number of major bleeding events, PaO2/FiO2 ratio | [108] |
Tenecteplase | NCT04505592 | RCT | Recruiting | 60 | 18–75 | Group 1: tenecteplase 0.25 mg/kg (maximum 25 mg), Group 2: tenecteplase 0.50 mg/kg (maximum 40 mg), Group 3: Control | Number of participants free of respiratory failure, Number of occurrences of bleeding | In-hospital deaths at 14 and 28 days, ventilator-free days, respiratory failure-free days, vasopressor-free days, Vasopressor doses at 24 and 72 h, PaO2/FiO2 ratio at 24 and 72 h, ICU-free days, Hospital length of stay, new-onset renal failure, need for renal replacement therapy | [102] |
Tenecteplase | NCT04558125 | RCT | Recruiting | 45 | 18–75 | Group 1: Tenecteplase infusion plus SOC, Group 2: Placebo infusion plus SOC | Percent improvement in shock index | Clinical status based upon 7-point scale | [103] |
rNAPc2 | NCT04655586 | RCT | Recruiting | 160 | 18–90 | Group 1: high dose of rNAPc2 (loading dose of 7.5 μg/kg SC on day 1 followed by 5 μg/kg SC on days 3 and 5), Group 2: low dose of rNAPc2 (loading dose of 5 μg/kg SC on day 1 followed by 3 μg/kg SC on days 3 and 5), Group 3: Heparin | Change in D-dimer level from Baseline to day 8, or day of discharge, Number of major or non-major clinically relevant bleeding events, Time to recovery within 30 days of randomization | Major or non-major clinically relevant bleeding events, bleeding events, Time to first occurrence of a composite of thrombotic events, all-cause mortality, change in tissue factor, interleukin-6 and high sensitivity C-reactive protein laboratory values | [97] |
Defibrotide | NCT04348383 | RCT | Recruiting | 150 | ≥ 18 years | Group 1: Defibrotide 25 mg/kg 24 h continuous infusion + SOC, Group 2: Placebo + SOC for 15 days | Clinical improvement on WHO scale | Mortality rate, serious adverse events, clinical improvement by NEWS2 scales, decrease of IL-6 levels, biologic response (lymphocytes count, D-dimer, CRP, LDH, CPK, Ferritin), radiological response | [104] |
Defibrotide | NCT04335201 | Clinical trial | Recruiting | 50 | ≥ 18 years | Defibrotide 25 mg/kg/day, infusion for 2 h, every 6 h (Defibrotide 6.25 mg/kg each dose) for 7 days | Attenuation of the progression of acute respiratory failure | Adverse events, duration of hospitalization, systemic inflammation, overall survival | [105] |
Defibrotide | NCT04530604 | Clinical trial | Active, not recruiting | 12 | 18–70 | Defibrotide 25 mg/kg/day every 6 h, each dose IV infused over 2 h for 7 days | Number of major hemorrhagic complications during 2 weeks | Overall survival, ventilator free survival, Number of ventilator-free days, improvement in oxygenation, change in the WHO ordinal scale | [106] |
Defibrotide | NCT04652115 | Clinical trial | Recruiting | 42 | 18–100 | Deibrotide IV infusion | The rate of adverse event of special interest (bleeding and hypotension) | – | [107] |