A placebo-controlled double blind trial of hydroxychloroquine in mild-to-moderate COVID-19

BackgroundThe efficacy of hydroxychloroquine in coronavirus disease 2019 (COVID-19) remains controversial. MethodsWe conducted a multicentre randomized double-blind placebo-controlled trial evaluating hydroxychloroquine in COVID-19 patients with at least one of the following risk factors for worsening: age [≥]75 years, age between 60 and 74 years, and presence of at least one comorbidity, or need for supplemental oxygen ([≤]3 L/min). Eligible patients were randomized in a 1:1 ratio to receive either 800mg hydroxychloroquine on Day 0 followed by 400mg per day for 8 days or a placebo. The primary endpoint was a composite of death or tracheal intubation within 14 days following randomization. Secondary endpoints included mortality and clinical evolution at Day 14 and 28, viral shedding at Day 5 and 10. ResultsThe trial was stopped after 250 patients were included due to a slowdown of the pandemic in France. The intention-to-treat population comprised 123 and 124 patients in the placebo and hydroxychloroquine groups, respectively. The median age was 77 years and 151 patients required oxygen therapy. The primary endpoint occurred in nine patients in the hydroxychloroquine group and eight patients in the placebo group (relative risk 1.12; 95% confidence interval 0.45- 2.80; P=0.82). No difference was observed between the two groups in any of the secondary endpoints. ConclusionIn this trial involving mainly older patients with mild-to-moderate COVID-19, patients treated with hydroxychloroquine did not experience better clinical or virological outcomes than those receiving the placebo.

Reliability and limits of transport-ventilators to safely ventilate severe patients in special surge situations.

BackgroundSeveral Intensive Care Units (ICU) have been overwhelmed by the surge of COVID-19 patients thus necessitating to extend ventilation capacity outside the ICU where air and oxygen pressure are not always available. Transport ventilators requiring only O2 source may be used to deliver volume-controlled ventilation. ObjectiveTo evaluate the performances of four transport ventilators compared to an ICU ventilator simulating severe respiratory conditions. Materials and methodsTwo pneumatic transport ventilators, (Oxylog 3000, Draeger; Osiris 3, Air Liquide Medical Systems) and two turbine transport ventilators (Elisee 350, ResMed; Monnal T60, Air Liquide Medical Systems) were compared to an ICU ventilator (Engstrom Carestation - GE Healthcare) using a Michigan training test lung. We tested each ventilator with different set volumes Vtset (350, 450, 550 ml) and different compliances (20 or 50 ml/cmH2O) and a resistance of 15 cmH2 0/L/sec based on values recently described in COVID-19 Acute Respiratory Distress Syndrome. Volume error was measured, as well as the trigger time delay during assist-control ventilation simulating spontaneous breathing activity with a P0.1 of 4 cmH20. ResultsGrouping all conditions, the volume error was 2.9 {+/-} 2.2 % for Engstrom Carestation; 3.6 {+/-} 3.9 % for Osiris 3; 2.5 {+/-} 2.1 % for Oxylog 3000; 5.4 {+/-} 2.7 % for Monnal T60 and 8.8 {+/-} 4.8 % for Elisee 350. Grouping all conditions, trigger delay was 42 {+/-} 4 ms, 65 {+/-} 5 ms, 151 {+/-} 14 ms, 51 {+/-} 6 and 64 {+/-} 5 ms for Engstrom Carestation, Osiris 3, Oxylog 3000, Monnal T60 and Elisee 350, respectively. ConclusionsIn special surge situations such as COVID-19 pandemic, most transport ventilators may be used to safely deliver volume-controlled ventilation in locations where only oxygen pressure supply is available with acceptable volume accuracy. Performances regarding triggering function are generally acceptable but vary across ventilators.