No abstract

No abstract

No abstract

ObjectivesTo characterise current COVID-19-related research activities.DesignCross-sectional analysis.SettingClinical trials registered with ClinicalTrials.gov testing interventions relevant to COVID-19.Data sourcesClinicalTrials.gov was searched for COVID-19 and related terms to identify trials registered between 1 December 2019 and 1 May 2020 that test interventions related to the COVID-19 pandemic.Main outcome measuresWe classified trials according to intervention type, and report key trial characteristics including recruitment status, location, funder type, target enrolment number, intervention model (single group, randomised or sequential assignment) and projected completion date.ResultsOf the 630 identified clinical trials related to COVID-19, 509 (81%) involved the study of drugs or biological agents. Of these trials of drugs and biologics, 305 (60%) use an open-label design, 43 (8%) are single blinded (participant only) and 161 (32%) are double blinded (participant and investigator). 94 (18%) of the drug/biological trials are non-randomised. Either hydroxychloroquine or chloroquine is administered as part of the study protocol in 152 (30%) of the drug/biological trials. The total planned enrolment for these hydroxychloroquine/chloroquine trials is over 200 000 participants, which represents 65% of the total planned enrolment for all registered trials of drugs or biologics. There are also at least 25 registered trials of azithromycin (n=53), convalescent plasma (n=38), lopinavir/ritonavir (n=30), stem cell treatments (n=29) and tocilizumab (n=25). 142 trials were registered in the first 3 months of 2020, and 488 trials were registered between 1 April and 1 May 2020.ConclusionsThese findings demonstrate a robust research response to the COVID-19 pandemic, though many of the currently planned and ongoing trials focus on a small number of potential therapies, and many also lack essential design features and power necessary to provide accurate treatment effect estimates.

Background: Resuscitation with crystalloid fluid is a cornerstone of pediatric septic shock treatment. However, the optimal type of crystalloid fluid is unknown. We aimed to determine the feasibility of conducting a pragmatic randomized trial to compare balanced (lactated Ringer's [LR]) with 0.9% normal saline (NS) fluid resuscitation in children with suspected septic shock.Methods: Open-label pragmatic randomized controlled trial at a single academic children's hospital from January to August 2018. Eligible patients were >6 months to <18 years old who were treated in the emergency department for suspected septic shock, operationalized as blood culture, parenteral antibiotics, and fluid resuscitation for abnormal perfusion. Screening, enrollment, and randomization were carried out by the clinical team as part of routine care. Patients were randomized to receive either LR or NS for up to 48 hours following randomization. Other than fluid type, all treatment decisions were at the clinical team's discretion. Feasibility outcomes included proportion of eligible patients enrolled, acceptability of enrollment via the U.S. federal exception from informed consent (EFIC) regulations, and adherence to randomized study fluid administration.Results: Of 59 eligible patients, 50 (85%) were enrolled and randomized. Twenty-four were randomized to LR and 26 to NS. Only one (2%) of 44 patients enrolled using EFIC withdrew before study completion. Total median (interquartile range [IQR]) crystalloid fluid volume received during the intervention window was 107 (60 to 155) mL/ kg and 98 (63 to 128) mL/kg in the LR and NS arms, respectively (p = 0.50). Patients randomized to LR received a median (IQR) of only 20% (13 to 32) of all study fluid as NS compared to 99% (64% to 100%) of study fluid as NS in the NS arm (absolute difference = 79%, 95% CI = 48% to 85%).C onclusions: A pragmatic study design proved feasible to study comparative effectiveness of LR versus NS fluid resuscitation for pediatric septic shock.From the