Medical Health Cluster

4 abril, 2022

Long‑term outcomes of dexamethasone 12 mg versus 6 mg in patients with COVID‑19 and severe hypoxaemia

Purpose:We assessed long‑term outcomes of dexamethasone 12 mg versus 6 mg given daily for up to 10 days in patients with coronavirus disease 2019 (COVID‑19) and severe hypoxaemia.Methods:We assessed 180‑day mortality and health‑related quality of life (HRQoL) using EuroQoL (EQ)‑5D‑5L index values and EQ visual analogue scale (VAS) in the international, stratified, blinded COVID STEROID 2 trial, which ran‑domised 1000 adults with confirmed COVID‑19 receiving at least 10 L/min of oxygen or mechanical ventilation in 26 hospitals in Europe and India. In the HRQoL analyses, higher values indicated better outcomes, and deceased patients were given a score of zero.Results:We obtained vital status at 180 days for 963 of 982 patients (98.1%) in the intention‑to‑treat population, EQ‑5D‑5L index value data for 922 (93.9%) and EQ VAS data for 924 (94.1%). At 180 days, 164 of 486 patients (33.7%) had died in the 12 mg group versus 184 of 477 (38.6%) in the 6 mg group [adjusted risk difference − 4.3%; 99% confidence interval (CI) − 11.7–3.0; relative risk 0.89; 0.72–1.09; P= 0.13]. The adjusted mean differences between the 12 mg and the 6 mg groups in EQ‑5D‑5L index values were 0.06 (99% CI − 0.01 to 0.12; P= 0.10) and in EQ VAS scores 4 (− 3 to 10; P= 0.22).

ntroduction Critical coronavirus disease 2019 (COVID-19) is characterised by severe pulmonary inflammation and high rates of death despite anti-inflammatory treatment [1]. Survivors from critical COVID-19 suffer from reduced healthrelated quality of life (HRQoL), including physical and mental problems, for months after hospital discharge [2]. Dexamethasone 6 mg daily for up to 10 days is recommended for patients with critical COVID-19 [3] based on the results of a meta-analysis of 7 randomised trials reporting reduced short-term mortality with the use of systemic corticosteroids [1]. Subsequently, the results of the COVID STEROID 2 trial suggested that dexamethasone 12 mg as compared with 6 mg may result in more days alive without life support at 28 days in patients with COVID-19 and severe hypoxaemia [adjusted mean difference 1.3 days (95% confidence interval 0.0–2.6)] [4]. In a pre-planned Bayesian analysis of the COVID STEROID 2 trial, the probability of benefit with 12 mg versus 6 mg was 94% for days alive without life support at 28 days and between 84 and 96% for all secondary outcomes assessed up to 90 days [5]. The effects of dexamethasone dosing on longer-term outcomes, including HRQoL, in patients with COVID19 and severe hypoxaemia are important for patients and should inform clinicians, guideline committee members and policymakers. Here we present the 180-day mortality and HRQoL results, which were pre-specified secondary outcome measures of the COVID STEROID 2 trial [6].

Methods Trial design The COVID STEROID 2 trial was an investigator-initiated, international, parallel-group, stratified, blinded randomised clinical trial. The trial protocol was approved by the relevant medicine agencies and ethics committees [4]. The trial protocol, statistical analysis plan and the primary report have all been published [4, 6] [also presented in Electronic Supplement Material (ESM 1)]. We prepared this report in accordance with the CONSORT checklist (ESM 2).

Trial sites and patients Patients were enrolled between August 27, 2020 and May 20, 2021 at 31 sites in 26 hospitals in Denmark, India, Sweden, and Switzerland. Eligible patients were 18 years or older, had confirmed SARS-CoV-2 infection and received (i) supplementary oxygen at a flow of at least 10 L/min independent of delivery system, (ii) non-invasive ventilation or continuous positive airway pressure for hypoxemia, or (iii) invasive mechanical ventilation. We mainly excluded patients for whom consent could not be obtained, who had received systemic corticosteroids for COVID-19 for 5 days or more or received systemic corticosteroids for other indications than COVID-19 in doses higher than 6 mg dexamethasone equivalents, and those with invasive fungal infection or active tuberculosis. The exclusion criteria and trial definitions are presented in the protocol (ESM 1) and in the primary publication [4, 6]. We obtained informed consent from the patients or their legal surrogates according to national regulations before enrolment. If consent was withdrawn or not granted, permission was sought from the patient or relatives to continue collection and use of trial data…

Créditos: Comité científico Covid

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