click on circles to display study description...

Ader (lopinavir/ritonavir), 2021 NCT04315948

lopinavir/ritonavir (n=-9) vs. standard of care (n=-9)

randomized controlled trial

Lopinavir-ritonavir
SoC plus lopinavir-ritonavir (400 mg lopinavir and 100 mg ritonavir orally twice a day for 14 days).

Standard of care

4 arms (1:1:1:1 ratio): SoC, lopinavir-ritonavir, lopinavir-ritonavir plus interferon, hydroxychloroquine. Supportive treatments: corticosteroids, anticoagulants or immunomodulatory agents were allowed, but not antivirals.

COVID 19 hospitalized

Open-label.

30 sites in France and 2 sites in Luxembourg.

Clinical status was measured on a 7-point ordinal scale: (1) not hospitalized, no limitation on activities; (2) not hospitalized, limitation on activities; (3) hospitalized, not requiring supplemental oxygen; (4) hospitalized, requiring supplemental oxygen; (5) hospitalized, on non-invasive ventilation or high-flow oxygen devices; (6) hospitalized, on invasive mechanical ventilation or ECMO; (7) death.

RECOVERY, 2020 NCT04381936

lopinavir/ritonavir (n=1616) vs. standard of care (n=3424)

randomized controlled trial

lopinavir-ritonavir
400 mg and 100 mg, respectively, by mouth for 10 days or until discharge, plus standard of care.

Standard of care
Standard of care alone.

Standard care in both groups.

COVID 19 hospitalized

Open-label

175 NHS hospitals in UK

SOLIDARITY (lopi/rito), 2020 NCT04315948

lopinavir/ritonavir (n=1399) vs. standard of care (n=1372)

randomized controlled trial

Lopinavir-ritonavir
Two tablets twice daily for 14 days. Each tablet contained 200mg Lopinavir (plus 50mg Ritonavir, to slow hepatic clearance of Lopinavir). Other formulations were not provided, so ventilated patients received no study Lopinavir while unable to swallow.

Standard of care.
Local standard of care alone.

COVID 19 hospitalized

age ≥18 years, hospitalized with a diagnosis of COVID-19, not known to have received any study drug, without anticipated transfer elsewhere within 72 hours, and, in the physician’s view, with no contra-indication to any study drug

Open-label

405 hospitals in 30 countries

Mortality during the original episode of hospitalization (follow-up ceased at discharge) not only in all patients but also in those with moderate COVID and in those with severe COVID (subsequently defined as ventilated when randomized).

Nojomi, 2020 IRCT20180725040596N2

lopinavir/ritonavir (n=50) vs. umifenovir (arbidol) (n=50)

randomized controlled trial

Lopinavir-ritonavir
Hydroxychloroquine (400 mg just on first day) followed by 400 mg Kaletra (Lopinavir-ritonavir) BD

Arbidol (umifenovir)
Hydroxychloroquine (400 mg BD on first day followed by 200 mg BD) followed by ARB (200 mg TDS) 7 to 14 days based on the severity of disease.

HCQ in both groups.

COVID 19 hospitalized

Open-label

single center, teaching hospital of Iran University of medical Sciences (IUMS), Tehran, Iran.

The criteria of improvement were relief of cough, dyspnea and fever.

ELACOI (lopinavir/ritonavir), 2020 NCT04252885

lopinavir/ritonavir (n=21) vs. standard of care (n=7)

randomized controlled trial

Lopinavir-ritonavir
Lopinavir (200mg) boosted by ritonavir (50mg) (oral, q12h, 500 mg each time for 7-14 days) monotherapy

Standard of care.
No antiviral medication. Supportive care and effective oxygen therapy if in need.

3 arms: lopinavir/ritonavir (n=21), arbidol=umifénovir (n=16) and standard of care (n=7).Standard of care in both groups.

COVID-19 mild to moderate

Open-label

China, single center

REMAP-CAP (lopinavir/ritonavir only), 2020 NCT02735707

lopinavir/ritonavir (n=268) vs. standard of care (n=377)

randomized controlled trial

Lopinavir/ritonavir
400 mg of lopinavir and 100 mg of ritonavir every 12h for 5 days minimum, up to a maximum of 14 days or until ICU discharge whichever occurred first. Patients with a gastric tube who were unable to swallow tablets, lopinavir-ritonavir (at the same dose) was administered as a 5-ml suspension every 12h or alternatively as two dissolved tablets or four crushed tablets (double dose).

Standard of care
No antiviral treatment.

COVID-19 severe or critically

≥18 years old, admitted with suspected or confrmed COVID-19, and were receiving respiratory or cardiovascular organ failure support in an intensive care unit (ICU). Organ support included the provision of invasive mechanical ventilation, noninvasive mechanical ventilation, high-fow nasal cannulae with a fow rate of at least 30 L per minute and a fractionalinspired oxygen concentration of 0.4 or higher, or the infusion of vasopressor or inotropes for shock.

Open-label.

99 sites across 8 countries.

In the register PE was: all-cause mortality (day 90); days alive and not receiving organ support in ICU (day 21).

Enrollment into the lopinavir-ritonavir arm was halted on November 19, 2020, after reaching the prespecifed futility threshold.

Cao, 2020 ChiCTR2000029308

lopinavir/ritonavir (n=99) vs. standard of care (n=100)

randomized controlled trial

Lopinavir–ritonavir
Lopinavir–ritonavir (400 mg and 100 mg, respectively) twice a day for 14 days, in addition to standard care.

Standard care
Standard care alone.

Both groups received standard care: supplemental oxygen,noninvasive and invasive ventilation, antibiotic agents, vasopressor support, renal-replacement therapy, and extracorporeal membrane oxygenation (ECMO).

COVID-19 severe or critically

Male and nonpregnant female patients 18 years of age or older were eligible if they had a diagnostic specimen that was positive on RT-PCR, had pneumonia confirmed by chest imaging, and had an oxygen saturation (Sao2) of 94% or less while they were breathing ambient air or a ratio of the partial pressure of oxygen (Pao2) to the fraction of inspired oxygen (Fio2)(Pao2:Fio2) at or below 300 mg Hg.

Open-label.

Single center, Jin Yin-Tan Hospital, Wuhan, Hubei Province, China.

The seven-category ordinal scale consisted of the following categories: 1, not hospitalized with resumption of normal activities; 2, not hospitalized,but unable to resume normal activities; 3, hospitalized, not requiring supplemental oxygen; 4,hospitalized, requiring supplemental oxygen; 5,hospitalized, requiring nasal high-flow oxygen therapy, noninvasive mechanical ventilation, or both; 6, hospitalized, requiring ECMO, invasive mechanical ventilation, or both; and 7, death.

Wuhan Infectious Diseases Hospital