Trial NCT04327401
Publication Tomazini BM, JAMA, 2020 (published paper)
Dates: 17/04/2020 to 23/06/2020
Funding: Mixed (Coalition COVID-19 Brazil; Laboratorios Farmaceuticos)
Conflict of interest: Yes
| Methods | |
| RCT Blinding: Unblinded | |
| Location :
Multicenter / Brazil Follow-up duration (days): 28 | |
| Inclusion criteria | 1) Age >/=18 years old
2) Probable or confirmed infection by SARS-CoV2 3) Intubated and mechanically ventilated 4) Moderate or severe ARDS according to Berlin criteria3 (Partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO2:FiO2) ratio of 200 or less, with positive end expiratory pressure (PEEP) of at least 5 cm of water, bilateral opacities and respiratory failure not fully explained by heart failure or fluid overload) 5) Within 48 hours of meeting criteria for moderate or severe ARDS |
| Exclusion criteria | 1) Pregnancy or active lactation
2) Known history of dexamethasone allergy 3) Corticosteroids use in non hospitalized patients in the past 15 days 4) Indication for corticosteroids use for other clinical conditions (e.g refractory septic shock) 5) Patients who used corticosteroids during hospital stay for more than one day 6) Use of immunosuppressive drugs 7) Cytotoxic chemotherapy in the past 21 days 8) Neutropenia due to hematological or solid malignancies with bone marrow invasion 9) Patients expected to die in the next 24 hours 10) Consent refusal for participation |
| Interventions | |
| Treatment
Dexamethasone 20 mg IV once a day for 5 days, then 10 mg IV once a day for 5 days |
|
| Control
Standard care Definition of Standard care: Each study center was encouraged to follow the best practice guidelines and their institutional protocol for the care of critically ill patients with COVID-19. All clinical interventions, such as use of antibiotics, ventilatory strategy, laboratory testing, and hemodynamic management were left at the discretion of the ICU team for both groups. | |
| Participants | |
| Randomized 299 participants (n1=151 / n2= 148) | |
| Characteristics of participants N=299 Mean age : 61.4 187 males Severity : Mild: n=0 / Moderate: n=0/ Severe: n=0 Critical: n=299 | |
| Primary outcome | |
| In the register Ventilator-free days [ Time Frame: 28 days after randomization ] | |
| In the report Ventilator-free days during the first 28 days, defined as the number of days alive and free from mechanical ventilation for at least 48 consecutive hours. | |
| Documents avalaible |
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 and protocol were used in data extraction and risk of bias assessment. The study was terminated early. As a result, the target sample size (350) was not achieved.
Quote: "On June 25, 2020, the DSMC discussed the implications of the results of the dexamethasone group in the RECOVERY (Randomized Evaluation of COVID-19 Therapy) trial, stating that given the study results,15 it was no longer ethical to continue the trial, which led to the recommendation to stop the trial. This recommendation was accepted by the CoDEX Steering Committee on June 25, 2020" There is no change from the trial registration in the intervention and control treatments, as well as, primary and secondary outcomes. |