Table 1.
Main characteristics of the overviewed studies and their findings.
| Studies, Year | Study Design | Main inclusion criteria | No of patients/Enrollment | Interventions/treatments | Findings |
|---|---|---|---|---|---|
| Cao, B. et al., 2020. Chinese Clinical Trial Register number, ChiCTR2000029308. |
Randomised, controlled, open-label trial | Hospitalised adult SARS-CoV-2 infected patients, and 94% SaO2 (ambient air) or a PaO2/Fio2 ratio < 300 mm Hg | 199 patients January 18, 2020–February 3, 2020. |
Patients randomly assigned (1:1) to receive either lopinavir-ritonavir (400 mg and 100 mg, respectively) b.id. for 14 days plus SOC or SOC alone. | Similar mortality rate observed in lopinavir – ritonavir group and SOC group (19.2% vs. 25.0%; difference, −5.8 percentage points; [95% CI, −17.3 to 5.7]). No benefit observed in Lopinavir–Ritonavir group vs SOC group. |
| Grein, J. et al., 2020. | Compassionate-use cohort. | Hospitalised adult SARS-CoV-2 infected patients and 94% SaO2 (ambient air) or receiving oxygen support | 53 patients January 25, 2020,- March 7, 2020 |
Patients received a 10-day course of Remdesivir (200 mg i.v. on day 1, and 100 mg daily for the remaining 9 days) | Clinical improvement observed in 36 of 53 patients (68%). |
| Beigel, J.H. et al., 2020. ClinicalTrials.gov Register number, NCT04280705. |
Double-blind, randomised, placebo-controlled trial | Hospitalised adult SARS-CoV-2 infected patients and ≤94% SaO2 | 1063 patients February 21, 2020–April 19, 2020 | Patients randomly assigned to receive either Remdesivir (200 mg on day 1, and 100 mg daily for up to 9 additional days) or placebo for up to 10 days | A 10-day course of Remdesivir was superior to placebo in number of days to recovery (median, 11 vs 15 days; recovery rate ratio, 1.32 [95% CI, 1.12 to 1.55]) and in recovery according to ordinal scale score at day 15 (OR, 1.50; 95% CI, 1.18 to 1.91). |
| Guaraldi, Gul et al., 2020. | Retrospective, observational cohort study | Adults (≥18 years) with severe COVID-19 pneumonia, admitted to tertiary care centres | 1351 patients February 21, 2020–April 30, 2020. |
All patients treated with SOC (ie, supplemental oxygen, hydroxychloroquine, azithromycin, antiretrovirals, and low molecular weight heparin), and a non-randomly patients' selected subset also received tocilizumab. | Reduced risk of invasive mechanical ventilation or death (AHR: 0·61, 95% [CI 0·40–0·92]; p = 0·020) observed in Tocilizumab group |
| Cantini, F. et al., 2020. | Observational, retrospective, longitudinal study | Hospitalised adults with COVID-19 moderate pneumonia | 191 patients February 20, 2020–May 5, 2020. | 113 patients treated for 2 weeks with Baricitinib 4 mg/day p.o. plus lopinavir/ritonavir tablets 250 mg/bid; Control-arm: 78 patients treated with hydroxychloroquine plus lopinavir/ritonavir. |
2-week case fatality rate was significantly lower in the Baricitinib-arm vs controls; ICU admission was requested in 0.88% (1/113) vs 17.9% (14/78) patients in baricitinib-arm vs control-arm; discharge rate was significantly higher in the Baricitinib-arm. |
| RECOVERY Collaborative Group, 2020. Clinicaltrial.gov Register number NCT04381936 |
- Randomised controlled, open-label trial | 1. Aged at least 18 years 2. Hospitalised 3. SARS-CoV-2 infection (suspected or confirmed) 4. No medical history that might, in the opinion of the attending clinician, put the patient at significant risk if he/she were to participate in the trial |
11,303 patients March 19, 2020–June 8, 2020 | Drug: Lopinavir-Ritonavir Drug: Corticosteroid Drug: Hydroxychloroquine Drug: Azithromycin Biological: Convalescent plasma Drug: Tocilizumab |
Among patients in ordinary care program, 28-day mortality was higher or intermediate in those needed ventilation or only oxygen, respectively. In dexamethasone group, mortality was 1/3 lower in ventilated patients and 1/5 lower in oxygen-treated subjects. Follow-up was completed for over 94% of the enrolled patients. |
| Tang, N. et al., 2020. | Retrospective, cohort study | Hospitalised adult patients with severe COVID-19 | 449 patients January 1, 2020–February 13, 2020 | All patients received antivirals and appropriate supportive therapies after admission. Ninety-nine (22.0%) patients received heparin treatment for up to 7 days. |
No difference in 28-day mortality in heparin users and nonusers (30.3% vs 29.7%, P = 0.910). The 28-day mortality of heparin users was lower than nonusers in patients with SIC score ≥4 (40.0% vs 64.2%, P = 0.029), or D-dimer >6-fold of upper limit of normal (32.8% vs 52.4%, P = 0.017). |
| Shen, Cao et al., 2020. | Case series | Adult COVID-19 patients and ARDS and the following criteria: severe pneumonia with rapid progression and continuously high viral load despite antiviral treatment; PaO2/FiO2 <300; and mechanical ventilation. | 5 patients January 20, 2020–March 25, 2020 |
Patients received convalescent plasma (between 10 and 22 days after admission) with a SARS-CoV-2-specific antibody (IgG) binding titer > 1:1000 and a neutralization titer > 40 obtained from 5 recovered COVID-19 patients | Improvement in clinical status |
| Goldman, J.D. et al., 2020 Clinicaltrial.gov Register number NCT04292899 |
Randomised, open-label trial | Hospitalised patients (age>12 years) SARS-CoV-2 infection confirmed by PCR within 4 days before randomization No mechanically ventilated |
397 patients | Patients randomly assigned (1:1) to receive Remdesivir i.v. for either 5 days or 10 days (200 mg on day 1 and 100 mg daily on subsequent days). | By day 14, a clinical improvement >2 points on the ordinal scale occurred in 64% of patients in 5-day group and in 54% in 10-day group. After adjustment for baseline clinical status, similar clinical status at day 14 was found in 10-day group and 5-day group (P = 0.14). |
| Adaptive Randomised trial for therapy of COrona virus disease 2019 at home with oral antivirals (ARCO-Home study), 2020 Eu CT number: 2020-001528-32 |
Multi-arm parallel randomised controlled clinical trial - (five-arms). | Adult (age ≥18 years) with confirmed SARS-CoV-2 infection, symptomatic for < 5 days before starting therapy and without criteria for immediate hospitalisation. | Expected sample size: 175–435 within two months of the start of the project (April 20, 2020). | Control arm. No specific antiviral treatment. Arm-1. One tablet of Darunavir (800 mg) + Cobicistat (150 mg) for 14 days. Arm-2. Two tablets of Hydroxychloroquine (each tablet = 200 mg) b.i.d. on day 1 and one tablet b.i.d. on day 2 to day 10. Arm-3. Two tablets of Lopinavir/Ritonavir b.i.d. for 14 days. Each tablet contains 200 mg of Lopinavir and 50 mg of Ritonavir. Arm-4. Nine tablets of favipiravir (each tablet = 200 mg) b.i.d. on day 1 and 4 tablets b.i.d. on day 2 to day 10. |
Ongoing No results available |
| A randomised, double-blind, placebo-controlled, multicenter study to evaluate the safety and efficacy of tocilizumab in patients with severe covid-19 pneumonia, 2020 Eu CT number: 2020-001154-22 |
Randomised, double-blind, placebo-controlled | Adult hospitalised patients with severe COVID-19 pneumonia | 330 patients (Date of Approval: March 30, 2020) | Patients randomly assigned (2:1) to receive blinded treatment of either Tocilizumab (one or two doses of tocilizumab i.v., at a dose of 8 mg/kg to a maximum of 800 mg per dose) or a matching placebo (one or two doses), respectively. | Ongoing No results available |
| Efficacy and Safety of Emapalumab and Anakinra in Reducing Hyperinflammation and Respiratory Distress in Patients With COVID-19 Infection, 2020 Clinicaltrial.gov Register number NCT04324021 |
Open label, controlled, parallel group, 3-arm | Hospitalised SARS-CoV-2 infected patients (age > 30 to < 80 years), diagnosis as per hospital routine | 54 patients (Date of Approval: April 20, 2020) |
Active arm: Emapalumab (infusion every 3rd day for a total 5 infusions, at day 1: 6 mg/kg and at the other days: 3 mg/kg) Active arm: Anakinra (400 mg/day in total, divided into 4 doses given every 6 h for 15 days)No Intervention: SOC according to local practice |
No results available |
| BARICIVID-19 STUDY: MultiCentre, randomised, Phase IIa clinical trial evaluating efficacy and tolerability of Baricitinib as add-on treatment of patients with COVID-19 compared to standard therapy, 2020 Eu CT number: 2020-001955-42 |
Multicenter randomised controlled PoC (phase IIa) clinical trial | Adult hospitalised patients COVID-19 pneumonia | 126 patients (Date of Approval: April 22, 2020) |
All patients were treated with SOC. 63 patients received baricitinib 4 mg p.o., 1 tablet daily for 14 days. Patients with eGFR >30 and < 60 mL/min and those with age >75 years was treated with ½ tablet daily (2 mg) for 14 days. The control group (63 patients) was treated with SOC |
No results available |
| U. S. National Library of Medicine. ClinicalTrial.gov, 2020 b. Convalescent Plasma vs. Standard Plasma for COVID-19, 2020 Clinicaltrial.gov Register number NCT04344535 |
Randomised, Parallel Assignment | Adults hospitalised with COVID-19 infection | 500 patients (Date of Approval: August 4, 2020) |
Active arm: Convalescent Plasma 450–550 mL of plasma containing anti-SARS-CoV-2 antibody titer ideally > 1:320 (minimum titer per FDA Guidelines for convalescent plasma).Control arm: Standard Donor Plasma 450–550 mL of plasma with low titer to anti-SARS-CoV-2 antibodies |
No results available |
Abbreviations: SaO2: oxygen saturation; PaO2/Fio2 ratio: partial oxygen pressure (PaO2)/inspired oxygen fraction (FiO2); b.i.d.: bis in die; SOC: standard of care; i.v.: intravenous; CI: confidence interval; OR: Odds ratio; ARDS: acute respiratory distress syndrome; PCR: polymerase-chain-reaction; AHR: adjusted hazard ratio; p.o.: per os.