From: Repurposed pharmacological agents for the potential treatment of COVID-19: a literature review
Study | Study design (number of participants) | Study arms (number of participants) | Endpoints | Results |
---|---|---|---|---|
Recovery Trial [82] | Randomised, open-label, controlled trial (n = 6425) | 1. Dexamethasone 6 mg once daily for 10 days (n = 2104) 2. Standard of care (n = 4321) | Primary: 28-day all-cause mortality Secondary: Time until hospital discharge; receipt of invasive mechanical ventilation; death | Significantly lower 28-day mortality in the dexamethasone group than in standard of care (22.9% vs 25.7%). Greater benefit in patients receiving invasive mechanical ventilation at baseline Shorter duration of hospitalization in the dexamethasone group (median, 12 days vs 13 days) Lower progression in the dexamethasone group to invasive mechanical ventilation in patients not receiving invasive mechanical ventilation at baseline |
Tomazini et al. CoDEX trial [83] | Randomised, open-label, controlled trial (n = 299) | 1. Dexamethasone 20 mg daily for 5 days, followed by 10 mg daily for 5 days (n = 151) 2. Standard of care (n = 148) | Primary: Ventilator-free days during the first 28 days Secondary: All-cause mortality at 28 days, 15-day clinical status; ICU-free days during the first 28 days, mechanical ventilation duration at 28 days; SOFA scores at 48 h, 72 h, and 7 days | Significantly higher mean number of days alive and free from mechanical ventilation in the dexamethasone group (6.6 days vs 4.0 days) No statistically significant difference in all-cause 28-day mortality (56.3% in dexamethasone vs 61.5% in control), ICU-free days at day 18 (mean, 2.1 in dexamethasone vs 2.0 in control), and duration of mechanical ventilation (12.5 days in dexamethasone vs 13.9 days in control) Significantly lower SOFA score at day 7 in the dexamethasone group |
Dequin et al. [84] | Randomised, double-blind, placebo-controlled trial (n = 149) | 1. Low-dose hydrocortisone 200 mg daily for 7 days, then 100 mg daily for 4 days and 50 mg daily for 3 days (n = 76) 2. Placebo (n = 73) | Primary: Treatment failure at day 21 (death or persistent dependency on mechanical ventilation or high-flow oxygen therapy) Secondary: Use of tracheal intubation; use of prone position, ECMO or inhaled nitric oxide; PaO2:FIO2 ratio at days 1 to 7 and on days 14 and 21; proportion of patients with and number of episodes of nosocomial infections | No statistically significant benefit of low-dose hydrocortisone in critically ill COVID-19 patients with acute respiratory failure Treatment failure at day 21 was 42.1% in the hydrocortisone group vs 50.7% in the placebo group) Requirement of intubation was 50% in the hydrocortisone and 75% in the placebo group No significant difference in use of prone positioning between the groups (47.4% in hydrocortisone vs 53.4% in placebo group) No significant difference in PaO2:FIO2 ratio trend between the groups Occurrence of at least one nosocomial infection by day 28 was 37.3% in the hydrocortisone vs 41.1% in the placebo group |
REMAP-CAP trial [85] | Randomised, open-label, controlled trial (n = 384) | 1. Hydrocortisone 50 or 100 mg every 6 h for 7 days (n = 137) 2. Shock-dependent course of hydrocortisone 50 mg every 6 h (n = 146) 3. No hydrocortisone (n = 101) | Primary: Organ support–free days within 21 days Secondary: In-hospital mortality; ICU and hospital length of stay; respiratory support–free days, cardiovascular organ support–free days; progression to invasive mechanical ventilation, ECMO or death | Median organ-support free days was 0 in fixed-dose hydrocortisone, 0 in shock-dependent hydrocortisone, and 0 in the control group The probabilities of superiority were 93% and 80% in the fixed-dose hydrocortisone and in the shock-dependant hydrocortisone groups, respectively, in comparison to the no-hydrocortisone group In-hospital mortality was 30% in fixed-dose, 26% in shock-dependant, and 33% in no-hydrocortisone group |
Jeronimo et al. Metcovid [86] | Randomised, double-blind, phase IIb, placebo-controlled trial (n = 393) | 1. Methylprednisolone 0.5 mg/kg twice daily for 5 days (n = 194) 2. Placebo (n = 199) | Primary: 28-day mortality Secondary: Early mortality at days 7 and 14; need for intubation by day 7; proportion of patients with PaO2/FiO2 < 100 by day 7 | No significant difference in primary or secondary outcomes between the groups 28-day mortality was 37.1% in the methylprednisolone vs 38.2% in the placebo group |