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ADjunctive coRticosteroid trEatment iN criticAlly ilL Patients With Septic Shock (ADRENAL)

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by The George Institute
Sponsor:
Collaborators:
National Health and Medical Research Council, Australia
Australian and New Zealand Intensive Care Society Clinical Trials Group
Information provided by (Responsible Party):
The George Institute
ClinicalTrials.gov Identifier:
NCT01448109
First received: October 5, 2011
Last updated: May 27, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Septic Shock
Drug: Hydrocortisone
Drug: Sterile air filled vial
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomised Blinded Placebo Controlled Trial of Hydrocortisone in Critically Ill Patients With Septic Shock

Resource links provided by NLM:


Further study details as provided by The George Institute:

Primary Outcome Measures:
  • All cause mortality at 90 days after randomisation [ Time Frame: 90 days after randomisation ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • All-cause mortality at 28 days and 6 months after randomisation [ Time Frame: 28 days and 6 months after randomisation ] [ Designated as safety issue: No ]
  • Time to resolution of shock [ Time Frame: MAP goal for >24 hours without vasopressors or inotropes. Up to 90 days after randomisation. ] [ Designated as safety issue: No ]
    Time to resolution of shock - defined as "the time taken to achieve a clinician prescribed mean arterial pressure (MAP) goal for >24 hours without vasopressors or inotropes.

  • Recurrence of shock [ Time Frame: Up to90 days after randomisation ] [ Designated as safety issue: No ]
    Recurrence of shock - defined as a new episode of shock after reversal of the initial episode.

  • Duration of ICU stay [ Time Frame: Up to 90 days after randomisation ] [ Designated as safety issue: No ]
  • Duration of hospital stay [ Time Frame: Up to 90 days after randomisation ] [ Designated as safety issue: No ]
  • Frequency and duration of mechanical ventilation [ Time Frame: Up to 90 days after randomisation ] [ Designated as safety issue: No ]
  • Duration of renal replacement therapy [ Time Frame: Up to 90 days after randomisation ] [ Designated as safety issue: No ]
  • Development of bacteraemia [ Time Frame: 2 and 14 days post randomisation ] [ Designated as safety issue: No ]
  • Bleeding requiring blood transfusions received in the ICU [ Time Frame: Up to 90 days after randomisation ] [ Designated as safety issue: No ]
  • Quality of Life assessment at 6 months. [ Time Frame: 6 months. ] [ Designated as safety issue: No ]

Estimated Enrollment: 3800
Study Start Date: June 2012
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Hydrocortisone 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.
Other Name: Solucortef
Placebo Comparator: Sterile air filled vial 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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Aged 18 years or older
  2. Documented site of infection, or strong suspicion of infection, with 2 of the 4 clinical signs of inflammation:

    • Core temperature > 38°C or < 35°C
    • Heart rate > 90 beats per minute
    • White cell count > 12 x 109/L or < 4 x 109/L or > 10% immature neutrophils
    • Respiratory rate > 20 breaths per minute, or PaCO2 < 32 mmHg, or mechanical ventilation.
  3. Being treated with mechanical ventilation at the time of randomisation
  4. Being treated with vasopressors or inotropes to maintain a systolic blood pressure > 90mmHg, or mean arterial blood pressure > 60mmHg, or a MAP target set by the treating clinician for maintaining perfusion
  5. Administration of vasopressors or inotropes for = 4 hours and present at time of randomisation.

Exclusion Criteria:

  1. Met all inclusion criteria more than 24 hours ago
  2. Clinician expects to prescribe systemic corticosteroids for an indication other than septic shock (not including nebulised or inhaled corticosteroid)
  3. Patients treated with etomidate
  4. Patients receiving treatment with Amphotericin B for systemic fungal infections at time of randomisation
  5. Patients with documented cerebral malaria at the time of randomisation
  6. Patients with documented strongyloides infection at the time of randomisation
  7. Death is deemed inevitable or imminent during this admission and either the attending physician, patient or surrogate legal decision maker is not committed to active treatment
  8. Death from underlying disease is likely within 90 days
  9. Patient has been previously enrolled in the ADRENAL study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01448109

Contacts
Contact: Dorrilyn Rajbhandari +61 410 442 828 drajbhandari@georgeinstitute.org.au

  Show 57 Study Locations
Sponsors and Collaborators
The George Institute
National Health and Medical Research Council, Australia
Australian and New Zealand Intensive Care Society Clinical Trials Group
Investigators
Study Chair: Balasubramanian Venkatesh The George Institute
  More Information

No publications provided

Responsible Party: The George Institute
ClinicalTrials.gov Identifier: NCT01448109     History of Changes
Other Study ID Numbers: GI-CCT372273
Study First Received: October 5, 2011
Last Updated: May 27, 2014
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by The George Institute:
Sepsis
Corticosteroid

Additional relevant MeSH terms:
Critical Illness
Shock
Shock, Septic
Disease Attributes
Infection
Inflammation
Pathologic Processes
Sepsis
Systemic Inflammatory Response Syndrome
Cortisol succinate
Hydrocortisone
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone acetate
Hydrocortisone-17-butyrate
Anti-Inflammatory Agents
Dermatologic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014