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.

     

Esophageal foreign body causing direct aortic injury.

Foreign bodies in the esophagus are uncommon causes of esophageal perforation. Many nonperforating cases are successfully managed by flexible gastroscopy. However, complicated foreign bodies such as those that result in esophageal perforation and vascular injury are best managed surgically. Gastroscopy remains the primary method of diagnosis. A case of a 59-year-old woman who developed retrosternal and intrascapular pain, odynophagia and hematemesis after eating fish is reported. Flexible gastroscopy showed arterial bleeding from the midthoracic esophagus. Computed tomography scan localized a 3 cm fish bone perforating the esophagus with surrounding hematoma. An aortogram did not reveal an actively bleeding aortoesophageal fistula. The fish bone was surgically removed and the patient recovered with no postoperative complications. This case illustrates the importance of early consideration for surgical intervention when confronted with a brisk arterial bleed from the esophagus with suggestive history of foreign body ingestion.     

Rhinitis Symptom Utility Index (RSUI) in Chinese Subjects: A Multiattribute Patient-preference Approach

Background: The Rhinitis Symptom Utility Index (RSUI), originally developed in the United States, consists of a patient-preference weighting scheme and a 10-item questionnaire measuring the severity and frequency of rhinitis related symptoms over a 14-day period. This study aimed to determine whether the Chinese RSUI could adopt the US-based multi-attribute utility function (MAUF) in scoring rhinitis symptoms. Methods: In a Hong Kong study, 116 Chinese adults with allergic rhinitis completed the RSUI questionnaire and 36-item Short-Form Health Survey (SF-36) after they had been seen by two otorhinolaryngologists for disease-severity ratings. Respondents then completed computer-administered direct preference measures, i.e., visual analogue scale (VAS) and standard gamble (SG) assessments. The VAS and SG data were used to estimate a MAUF for the Chinese-based RSUI. Results: The derived MAUF was somewhat different than the one developed for the US RSUI. Test–retest reliability for the Chinese RSUI was satisfactory (ICC = 0.71, p<0.001). Scores differentiated among cases with mild, moderate, and severe symptoms (p<0.001); and between those who did and did not require medications to control symptoms (p = 0.031). Findings were significantly correlated with SF-36 domain scores (r = 0.19 to 0.37; p=0.041 to <0.001). When the US-based scoring function was applied to the Chinese subjects, the resulting mean RSUI score was significantly lower (p<0.001). Comparisons between directly measured VAS and SG scores between the US and Chinese samples, demonstrated significant differences (all p<0.05), with the US subjects consistently rating rhinitis symptoms as worse than Chinese subjects. Conclusions: The Chinese RSUI has good measurement properties that reflect patient preferences from the Chinese. Results suggest that there are differences in preference rating between US and Chinese subjects and that use of the US-based preference function for the RSUI would bias the measurement of rhinitis symptom outcomes in Chinese subjects.