Low-dose hydrocortisone in patients with COVID-19 and severe hypoxia (COVID STEROID) trial—Protocol and statistical analysis plan

Introduction

Severe acute respiratory syndrome coronavirus-2 has caused a pandemic of coronavirus disease (COVID-19) with many patients developing hypoxic respiratory failure. Corticosteroids reduce the time on mechanical ventilation, length of stay in the intensive care unit and potentially also mortality in similar patient populations. However, corticosteroids have undesirable effects, including longer time to viral clearance. Clinical equipoise on the use of corticosteroids for COVID-19 exists.

Methods

The COVID STEROID trial is an international, randomised, stratified, blinded clinical trial. We will allocate 1000 adult patients with COVID-19 receiving ≥10 L/min of oxygen or on mechanical ventilation to intravenous hydrocortisone 200 mg daily vs placebo (0.9% saline) for 7 days. The primary outcome is days alive without life support (ie mechanical ventilation, circulatory support, and renal replacement therapy) at day 28. Secondary outcomes are serious adverse reactions at day 14; days alive without life support at day 90; days alive and out of hospital at day 90; all-cause mortality at day 28, day 90, and 1 year; and health-related quality of life at 1 year. We will conduct the statistical analyses according to this protocol, including interim analyses for every 250 patients followed for 28 days. The primary outcome will be compared using the Kryger Jensen and Lange test in the intention to treat population and reported as differences in means and medians with 95% confidence intervals.

Discussion

The COVID STEROID trial will provide important evidence to guide the use of corticosteroids in COVID-19 and severe hypoxia.

     

The Repository of Antemortem Injury Response (REPAIR): an online database for skeletal injuries of known ages

An accurate assessment of time since fracture is an essential component of abuse and death investigations; however, little evidence-based research exists on dating fractures, especially those of the cranial vault. This is primarily due to difficulties in procuring human fracture specimens of known posttraumatic survival times. The aim of this article is to introduce a new database through which limitations imposed by sample procurement may be mitigated. The Repository of Antemortem Injury Response (REPAIR) is a digitally accessible database of cranial vault fractures of known ages with extensive contextual information and visual documentation in the form of photography, radiography, and histological photomicrographs. This repository is a multifunctional tool that serves as a case submission portal for cranial fractures of known posttraumatic survival time, a sample database for research on fracture healing and rates of repair, a resource for comparative assessments of cranial fractures in forensic casework, and an educational tool for healing fracture histomorphology.