NCT01448109

ADjunctive coRticosteroid trEatment iN criticAlly ilL Patients With Septic Shock

A Randomised Blinded Placebo Controlled Trial of Hydrocortisone in Critically Ill Patients With Septic Shock

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 3,800 (actual)
• Sponsor: The George Institute · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

Primary Objective To evaluate the impact of intravenous hydrocortisone versus placebo on all cause mortality at 90 days in critically ill patients with septic shock. The hypothesis is that hydrocortisone, compared to placebo, reduces 90-day all-cause mortality in patients admitted to an ICU with septic shock. 'Shock' is defined as the need for vasopressors or inotropes to maintain a systolic blood pressure \> 90 millimetres of mercury (mmHg), or mean arterial blood pressure \> 60mmHg or a mean arterial pressure (MAP) target set by the treating clinician for maintaining perfusion. 'Septic shock' is shock that is secondary to sepsis Secondary Objectives To assess the impact of intravenous hydrocortisone versus placebo on the recovery from, and the complications of, septic shock and the development of treatment related adverse reactions. Study Design This study is a multi centre, randomised, blinded, placebo controlled trial comparing intravenous hydrocortisone with placebo in critically ill patients with septic shock. Randomisation will be achieved via a secure interactive web based system using permuted block minimisation. Randomisation will be stratified by participating site and by operative or non-operative admission to the ICU. The primary endpoint for this trial will be death from all causes at 90 days. Pre defined sub groups will include the following categories: * Operative (admitted to ICU from operating theatre or recovery room) versus non-operative admission. * Dose of adrenaline or noradrenaline at randomisation - ≤ 15 mcg / minute versus \> 15 mcg / minute. 3,800 patients will be enrolled in this study at approximately 50 - 60 study sites. Eligible patients will be randomised to receive either intravenous hydrocortisone 200mg or placebo per day for 7 days. For all patients, data will be collected at baseline and then daily whilst the patient is in the ICU. Patients will be followed up to day 14, regardless of where the patient resides in the hospital, to monitor the development of bacteraemia. Additional follow up will occur at 90 days and at 6 months post randomisation.

Conditions

• Septic Shock

Interventions

Type	Name	Description
DRUG	Hydrocortisone	Hydrocortisone 100mg vial (blinded) is reconstituted with 2ml of water for Injection, agitated for 20 seconds, rested for 3 minutes, contents of vial aspirated and added to 100ml bag of normal saline or 5% dextrose and given intravenously as a continuous infusion at rate of 200mg/per day for 7 days.
DRUG	Sterile air filled vial	the "sterile air filled vial" (blinded) is reconstituted with 2ml of water for Injection, agitated for 20 seconds, rested for 3 minutes, contents of vial aspirated and added to 100ml bag of normal saline or 5% dextrose and given intravenously as a continuous infusion. 2 sterile air filled vials per day for 7 days

Timeline

• Start date: 2012-06-13
• Primary completion: 2017-10-22
• Completion: 2017-11-20
• First posted: 2011-10-07
• Last updated: 2017-12-12

Locations

70 sites across 5 countries: Australia, Denmark, New Zealand, Saudi Arabia, United Kingdom