Trial NCT04381936
Publication Horby P, Lancet, 2020 (published paper)
Dates: 2020-03-19 to 2020-06-29
Funding: Mixed (NIHR Oxford Biomedical Research Centre; Wellcome Trust; Bill and Melinda Gates Foundation; Health Data Research UK; UK Department for International Development; NIHR Health Protection Unit in Emerging and Zoonotic Infect)
Conflict of interest: No
| Methods | |
| RCT Blinding: Unblinded | |
| Location :
Multicenter / UK Follow-up duration (days): 28 | |
| Inclusion criteria | Patients admitted to hospital were eligible for the study if they had clinically suspected or laboratory confirmed SARS-CoV-2 infection and no medical history that might, in the opinion of the attending clinician, put the patient at substantial risk if they were to participate in the trial. Initially, recruitment was limited to patients who were aged at least 18 years, but from May 9, 2020, this age limit was removed. |
| Exclusion criteria | Report:
Patients with severe hepatic insufficiency or who were using medicinal products that are highly dependent on cytochrome P450 3A4 for clearance and for whom elevated plasma concentrations would be associated with serious or life-threatening events (in line with the summary of product characteristics). Registry: If the attending clinician believes that there is a specific contra-indication to one of the active drug treatment arms or that the patient should definitely be receiving one of the active drug treatment arms then that arm will not be available for randomisation for that patient. For patients who lack capacity, an advanced directive or behaviour that clearly indicates that they would not wish to participate in the trial would be considered sufficient reason to exclude them from the trial. |
| Interventions | |
| Treatment
Lopinavir-Ritonavir lopinavir 400 mg plus ritonavir 100 mg orally every 12 hours for 10 days |
|
| Control
Standard care Definition of Standard care: All patients will receive usual care for the participating hospital... It is expected that usual standard of care alone will evolve. | |
| Participants | |
| Randomized 5040 participants (n1=1616 / n2= 3424) | |
| Characteristics of participants N=5040 Mean age : 66.3 3077 males Severity : Mild: n=1321 / Moderate: n=*/ Severe: n=* Critical: n=204 | |
| Primary outcome | |
| In the register All-cause mortality [Time Frame: Within 28 days after randomisation] | |
| In the report 28-day all-cause mortality | |
| Documents available |
Protocol Yes. In English Statistical plan Yes Data-sharing stated Yes |
| Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review |
Some concerns |
| General comment | In addition to all available versions of the published article, the study registry, statistical analysis plan, supplementary appendix and protocol were used in data extraction and risk of bias assessment. This trial is part of a large ongoing study with comparisons of multiple treatments for COVID-19 with standard care. As of October 2020 the trial continues to study the effects of azithromycin, tocilizumab, convalescent plasma, and REGN-CoV2. Recruitment to the lopinavir–ritonavir arm was terminated because the independent data monitoring committee, chief investigators and steering committee concluded that the data showed no beneficial effect of lopinavir–ritonavir in patients admitted to hospital with COVID-19. There were no substantive changes in treatments or outcomes between the published article and study registries, the trial protocol and statistical analysis plan. |