Trial NCT04321278
Publication Furtado RHM, Lancet, 2020 (published paper)
Dates: 28/03/2020 to 19/05/2020
Funding: Mixed (COALITION COVID-19 Brazil; EMS)
Conflict of interest: Yes
| Methods | |
| RCT Blinding: Unblinded | |
| Location :
Multicenter / Brazil Follow-up duration (days): 29 | |
| Inclusion criteria | Patients who were at least 18 years and were admitted to hospital with suspected or confirmed COVID-19 with fewer than 14 days since symptom onset. Additionally, patients needed to have at least one of the following severity criteria: use of oxygen supplementation of more than 4 L/min flow; use of high-flow nasal cannula; use of non-invasive positive-pressure ventilation; or use of mechanical ventilation. |
| Exclusion criteria | Refusal to provide consent for the study by the patient or their legal guardian; Hypersensitivity to any of the drugs used in the study (Azithromycin or Hydroxychloroquine); Having either more than 48 hours under prior use of the study medications (Azithromycin or Hydroxychloroquine); symptom onset greater than 14 days; long QT syndrome or severe ventricular arrhythmias; QTc> = 480ms; patients with do not resuscitate order or under exclusive palliative care; know history of liver disease or cirrhosis or abnormal liver enzyme tests above three times the upper limit values (alanine aminotransferase -ALT and aspartate aminotransferase - AST); known history of retinopathy or macular degeneration; known history of pancreatitis; concomitant use of medications that alter the absorption or excretion of azithromycin or hydroxychloroquine; use of medications known to prolong QTc interval; use of psychoactive drugs, and breastfeeding and/or pregnancy women. |
| Interventions | |
| Treatment
Azithromycin + Hydroxychloroquine Azithromycin: 500 mg orally, by nasogastric tube or IV once a day for 10 days. Hydroxychloroquine: 400 mg orally or by nasogastric tube twice a day for 10 days |
|
| Control
Hydroxychloroquine (400mg) Duration : 10 days | |
| Participants | |
| Randomized 447 participants (n1=237 / n2= 210) | |
| Characteristics of participants N=447 Mean age : NR 286 males Severity : Mild: n=0 / Moderate: n=*/ Severe: n=* Critical: n=225 | |
| Primary outcome | |
| In the register Evaluation of the clinical status [ Time Frame: 15 days after randomization ] | |
| In the report Clinical status, measured at 15 days using a six-level ordinal scale | |
| Documents available |
Protocol Yes. In English Statistical plan Yes Data-sharing stated NR |
| 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 and protocol were used in data extraction and risk of bias assessment. The study was terminated early due faster than anticipated enrolment. The study achieved the target sample size specified in the registry. There was no change from the trial registration in the intervention and control treatments nor the primary and secondary outcomes.
The extraction and assessment were in accordance with the original statistical analysis plan using the intention-to-treat population (retrieved from the Supplementary Appendix) vs. the modified intention-to-treat population reported in the paper. Quote: "As of May 13, 2020, the protocol was amended so that the main analysis would be done in a modified ITT (mITT) population that included only patients diagnosed with COVID-19 confirmed through molecular methods or serological testing. This decision was made by the executive committee before the first interim analysis from the data safety monitoring board while masked to study results. The reason for this decision was to include in the primary analysis only those patients more likely to benefit from the study intervention, (ie, those ones with confirmed SARS-CoV-2 infection)." |