NCT01448109: ADRENAL

ADjunctive coRticosteroid trEatment iN criticAlly ilL Patients With Septic Shock

Completed Phase 4 Last updated 12 December 2017

What this trial tests

Phase 4 trial testing Hydrocortisone in Septic Shock in 3,800 participants. Completed in 20 November 2017.

Timeline

13 June 2012

Primary endpoint
22 October 2017

20 November 2017

Quick facts

Lead sponsor	The George Institute
Phase	Phase 4
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	3,800
Start date	13 June 2012
Primary completion	22 October 2017
Estimated completion	20 November 2017
Sites	70 locations across Denmark, New Zealand, Saudi Arabia, United Kingdom, Australia

Drugs / interventions tested

• Hydrocortisone (hydrocortisone) — full drug profile →
• Sterile air filled vial — full drug profile →

Conditions studied

• Septic Shock — all drugs for Septic Shock →

Sponsor

The George Institute

Who can join

18 and older, any sex, with Septic Shock. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

The purpose of this study is to find out whether adult patients admitted to the Intensive Care Unit with septic shock who are given hydrocortisone compared to placebo (a dummy solution), will have an improved rate of survival 90 days later.

Septic shock is the result of an infection, which triggers a complex response by the body (the inflammatory response) that causes a decrease in blood pressure and subsequently one or more organ systems to fail when blood supply to these organs is reduced. This may result in poor recovery and death. About a quarter of the people who suffer septic shock that is not rapidly reversed, will die.

When patients are admitted to Intensive Care with sepsis and/or septic shock they receive a number of therapies. These include fluids given through a drip, antibiotics, drugs to boost your blood pressure and other organ systems.

In addition to these therapies, steroids (hydrocortisone) are sometimes administered. Whether steroids are useful or not in the treatment of severe infections has been studied for more than 50 years. Previous research has suggested that the use of low dose steroid may have shortterm 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. This study would allow doctors to make informed decisions about whether the addition of low dose steroid therapy is better for patients with septic shock in intensive care.

The study will include 3800 intensive care patients who have septic shock. Each enrolled patient will be randomised to receive either Hydrocortisone 200mg or placebo daily for 7 days as a continuous intravenous infusion while in intensive care. The patient will be followed for 90 days. If the patient is discharged prior to 90 days a telephone call will be made for the followup information. At six months the patient will be contacted again for completion of a quality of life questionnaire.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Adjunctive Glucocorticoid Therapy in Patients with Septic Shock.
   Venkatesh B, Finfer S, Cohen J, Rajbhandari D, et al · · 2018 · cited 681× · PMID 29347874 · DOI 10.1056/nejmoa1705835
2. Effectiveness of Fludrocortisone Plus Hydrocortisone versus Hydrocortisone Alone in Septic Shock: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.
   Teja B, Berube M, Pereira TV, Law AC, et al · · 2024 · cited 30× · PMID 38271488 · DOI 10.1164/rccm.202310-1785oc
3. Emerging therapeutic targets of sepsis-associated acute kidney injury.
   Swaminathan S, Rosner MH, Okusa MD. · · 2015 · cited 29× · PMID 25795498 · DOI 10.1016/j.semnephrol.2015.01.005
4. Update in sepsis guidelines: what is really new?
   Plevin R, Callcut R. · · 2017 · cited 22× · PMID 29766091 · DOI 10.1136/tsaco-2017-000088
5. In Search of a Cure for Sepsis: Taming the Monster in Critical Care Medicine.
   Okeke EB, Uzonna JE. · · 2016 · cited 19× · PMID 26771196 · DOI 10.1159/000442469
6. Corticosteroid treatment for community-acquired pneumonia--the STEP trial: study protocol for a randomized controlled trial.
   Blum CA, Nigro N, Winzeler B, Suter-Widmer I, et al · · 2014 · cited 17× · PMID 24974155 · DOI 10.1186/1745-6215-15-257
7. Core elements of general supportive care for patients with sepsis and septic shock in resource-limited settings.
   Mer M, Schultz MJ, Adhikari NK, European Society of Intensive Care Medicine (ESICM) Global Intensive Care Working Group and the Mahidol–Oxford Research Unit (MORU), et al · · 2017 · cited 12× · PMID 28620804 · DOI 10.1007/s00134-017-4831-z
8. Steroids are part of rescue therapy in ARDS patients with refractory hypoxemia: no.
   Thompson BT, Ranieri VM. · · 2016 · cited 12× · PMID 26883256 · DOI 10.1007/s00134-016-4255-1