ANZICS CTG Endorsed Study
Adjunctive glucocorticoid therapy in patients with septic shock
Septic shock is the result of an infection, which triggers an inflammatory response that causes a decrease in blood pressure and subsequently one or more organ failures. About a quarter of the people who suffer septic shock that is not rapidly reversed, will die. Whether steroids are useful or not in the treatment of septic shock has been studied for more than 50 years. Previous research has suggested that the use of low dose steroid may have short term benefits in improving the circulation. However, there is no agreement amongst doctors around the world about whether treatment with or without low dose steroids improves the overall recovery and survival in patients with septic shock.
Study Population and Methods
The purpose of this study is to find out whether adult patients admitted to the Intensive Care Unit with septic shock who are given hydrocortisone200mg compared to placebo daily for 7 days continuous intravenous infusion while in intensive care, will have an improved rate of survival 90 days later. The study included 3800 adult intensive care patients who had septic shock. The primary outcome being all cause mortality at 90 days after randomisation. Secondary endpoints included shock resolution, length of ICU and hospital stay, new episodes of bacteraemia/fungaemia, organ failure, 28 day mortality and Quality Adjusted Life Years (QALY).
Study Recruitment of the 3800th patient was completed on 21st April 2017. There was a total of 69 sites, with 45 sites in Australia, 8 sites in New Zealand, 3 sites in Kingdom of Saudi Arabia, 12 sites in United Kingdom and 1 site in Denmark. The study was presented on 19 January 2018 at the Critical Care Review meeting in Belfast, Ireland and was streamed live on YouTube. The main paper was published and released at the same time by the New England Journal of Medicine.
A Health Economic Analysis will be completed including the quality of life information.
Among the patients with septic shock undergoing mechanical ventilation, a continuous infusion of hydrocortisone did not result in lower 90-day mortality than placebo. This effect did not differ in any of the six pre-specified subgroups. It was observed that there was a more rapid resolution of shock and a lower incidence of blood transfusions among patients who received hydrocortisone than among those who received placebo. Patients who had been assigned to receive hydrocortisone had a shorter time to ICU discharge and earlier cessation of the initial episode of mechanical ventilation. A number of sub-studies will be published in 2019.
Bala Venkatesh (Chair), Yaseen Arabi, Rinaldo Bellomo, Jeremy Cohen, Maryam Correa, Simon Finfer, Parisa Glass, Meg Harward, Chris Joyce, Colin McArthur, John Myburgh, Anders Perner, Dorrilyn Rajbhandari (Project Manager), Andrew Rhodes, and Steve Webb.
The George Institute for Global Health
Balasubramanian Venkatesh, Simon Finfer, Jeremy Cohen, Dorrilyn Rajbhandari, Yaseen Arabi, Rinaldo Bellomo, Laurent Billot, Maryam Correa, Parisa Glass, Meg Harward, Christopher Joyce, Qiang Li, Colin McArthur, Anders Perner, Andrew Rhodes, Kelly Thompson, Steve Webb and John Myburgh for the ADRENAL Trial Investigators of the Australian-New Zealand Intensive Care society Clinical Trials Group. Adjunctive Glucocorticoid Therapy in Patients with Septic Shock. N Engl J Med 2018 Mar 19;378(9):797-808. Epub 2018 Jan 19