Table 2.

Ongoing registered clinical trials of thrombolytics for the management of COVID-19

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]

rt-PA recombinant tissue-Plasminogen Activator, paO₂/FiO₂ arterial oxygen partial to fractional inspired oxygen, SOFA sequential organ failure assessment, ICU intensive care, MV mechanical ventilation, ADR adverse drug reaction, NEWS2 National Early Warning Score 2, NIAID National Institute of Allergy and Infectious Diseases, SaO₂ oxygen saturation, SOC Standard of Care, rNAPc2 recombinant nematode anticoagulant protein c2, CRP C-reactive protein, LDH lactate dehydrogenase, CPK creatine Phosphokinase