ADjunctive coRticosteroid trEatment iN criticAlly ilL Patients With Septic Shock

NCT ID: NCT01448109

Last Updated: 2017-12-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

3800 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-06-13

Study Completion Date

2017-11-20

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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

See the medical conditions and disease areas that this research is targeting or investigating.

Septic Shock

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Hydrocortisone

Group Type ACTIVE_COMPARATOR

Hydrocortisone

Intervention Type DRUG

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.

Sterile air filled vial

Group Type PLACEBO_COMPARATOR

Sterile air filled vial

Intervention Type DRUG

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

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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.

Intervention Type 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

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Solu-Cortef

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

National Health and Medical Research Council, Australia

OTHER

Sponsor Role collaborator

Australian and New Zealand Intensive Care Society Clinical Trials Group

NETWORK

Sponsor Role collaborator

The George Institute

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Balasubramanian Venkatesh

Role: STUDY_CHAIR

The George Institute

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Blacktown Hospital

Blacktown, New South Wales, Australia

Site Status

Royal Prince Alfred Hospital

Camperdown, New South Wales, Australia

Site Status

St Vincent's Hospital

Darlinghurst, New South Wales, Australia

Site Status

Gosford Hospital

Gosford, New South Wales, Australia

Site Status

St George Hospital

Kogarah, New South Wales, Australia

Site Status

Liverpool Hospital

Liverpool, New South Wales, Australia

Site Status

John Hunter Hospital

Newcastle, New South Wales, Australia

Site Status

Nepean Hospital

Penrith, New South Wales, Australia

Site Status

Prince of Wales Hospital

Randwick, New South Wales, Australia

Site Status

Royal North Shore Hospital

St Leonards, New South Wales, Australia

Site Status

The George Institute for Global Health

Sydney, New South Wales, Australia

Site Status

Tamworth Rural Referral Hospital

Tamworth, New South Wales, Australia

Site Status

Tweed Heads District Hospital

Tweed Heads, New South Wales, Australia

Site Status

Calvary Mater Hospital (Newcastle)

Waratah, New South Wales, Australia

Site Status

Wollongong Hospital

Wollongong, New South Wales, Australia

Site Status

Royal Darwin Hospital

Darwin, Northern Territory, Australia

Site Status

Wesley Hospital

Auchenflower, Queensland, Australia

Site Status

Prince Charles Hospital

Brisbane, Queensland, Australia

Site Status

Mater Health Services

Brisbane, Queensland, Australia

Site Status

Gold Coast University Hospital

Gold Coast, Queensland, Australia

Site Status

Royal Brisbane and Women's Hospital

Herston, Queensland, Australia

Site Status

Ipswich Hospital

Ipswich, Queensland, Australia

Site Status

Logan Hospital

Logan City, Queensland, Australia

Site Status

Mackay Base Hospital

Mackay, Queensland, Australia

Site Status

Nambour Hospital

Nambour, Queensland, Australia

Site Status

Redcliffe Hospital

Redcliffe, Queensland, Australia

Site Status

Toowoomba Hospital

Toowoomba, Queensland, Australia

Site Status

Townsville Hospital

Townsville, Queensland, Australia

Site Status

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Site Status

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Site Status

Lyell McEwin Hospital

Elizabeth Vale, South Australia, Australia

Site Status

The Queen Elizabeth Hospital

Woodville South, South Australia, Australia

Site Status

Royal Hobart Hospital

Hobart, Tasmania, Australia

Site Status

Bendigo Hospital

Bendigo, Victoria, Australia

Site Status

Monash Medical Centre

Clayton, Victoria, Australia

Site Status

Northern Hospital

Epping, Victoria, Australia

Site Status

St Vincent's Hospital (Melbourne)

Fitzroy, Victoria, Australia

Site Status

Footscray Hospital

Footscray, Victoria, Australia

Site Status

Geelong Hospital (Barwon Health)

Geelong, Victoria, Australia

Site Status

Austin Hospital

Heidelberg, Victoria, Australia

Site Status

Royal Melbourne Hospital

Parkville, Victoria, Australia

Site Status

Sunshine Hospital

St Albans, Victoria, Australia

Site Status

Fremantle Hospital

Fremantle, Western Australia, Australia

Site Status

Fiona Stanley Hospital

Murdoch, Western Australia, Australia

Site Status

Royal Perth Hospital

Perth, Western Australia, Australia

Site Status

St John of God Hospital-Murdoch

Perth, Western Australia, Australia

Site Status

Rigshospitalet

Copenhagen, , Denmark

Site Status

North Shore Hospital

North Shore, Auckland, New Zealand

Site Status

Waikato Hospital

Hamilton, NZ, New Zealand

Site Status

Auckland City Hospital (CVICU)

Auckland, , New Zealand

Site Status

Auckland City Hospital (DCCM)

Auckland, , New Zealand

Site Status

Middlemore Hospital

Auckland, , New Zealand

Site Status

Christchurch Hospital

Christchurch, , New Zealand

Site Status

Tauranga Hospital

Tauranga, , New Zealand

Site Status

Wellington Hospital

Wellington, , New Zealand

Site Status

King Abdulaziz Medical City

Riyadh, , Saudi Arabia

Site Status

King Khalid University Hospital, King Saud University

Riyadh, , Saudi Arabia

Site Status

King Fahad Medical City

Riyadh, , Saudi Arabia

Site Status

Bristol Royal Infirmary

Bristol, England, United Kingdom

Site Status

Ashford & St.Peter's NHS Foundation Trust

Chertsey, England, United Kingdom

Site Status

Queen Alexandra Hospital (Portsmouth)

Cosham, England, United Kingdom

Site Status

Queen Elizabeth Hospital Birmingham

Edgbaston, England, United Kingdom

Site Status

Royal Surrey County Hospital

Guildford, England, United Kingdom

Site Status

Lewisham Healthcare NHS Trust

London, England, United Kingdom

Site Status

Guy's and St Thomas' HNS Foundation Trust

London, England, United Kingdom

Site Status

King's College Hospital NHS Foundation Trust

London, England, United Kingdom

Site Status

St Georges Healthcare NHS Trust

London, England, United Kingdom

Site Status

Freeman Hospital

Newcastle upon Tyne, England, United Kingdom

Site Status

University Hospital Southampton

Southampton, England, United Kingdom

Site Status

Royal Gwent Hospital

Newport, Wales, United Kingdom

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Australia Denmark New Zealand Saudi Arabia United Kingdom

References

Explore related publications, articles, or registry entries linked to this study.

Daubney ER, D'Urso S, Cuellar-Partida G, Rajbhandari D, Peach E, de Guzman E, McArthur C, Rhodes A, Meyer J, Finfer S, Myburgh J, Cohen J, Schirra HJ, Venkatesh B, Evans DM. A Genome-Wide Association Study of Serum Metabolite Profiles in Septic Shock Patients. Crit Care Explor. 2024 Jan 17;6(1):e1030. doi: 10.1097/CCE.0000000000001030. eCollection 2024 Jan.

Reference Type DERIVED
PMID: 38239409 (View on PubMed)

Li W, Cornelius V, Finfer S, Venkatesh B, Billot L. Adaptive designs in critical care trials: a simulation study. BMC Med Res Methodol. 2023 Oct 18;23(1):236. doi: 10.1186/s12874-023-02049-6.

Reference Type DERIVED
PMID: 37853343 (View on PubMed)

Venkatesh B, Finfer S, Cohen J, Rajbhandari D, Arabi Y, Bellomo R, Billot L, Correa M, Glass P, Harward M, Joyce C, Li Q, McArthur C, Perner A, Rhodes A, Thompson K, Webb S, Myburgh J; ADRENAL Trial Investigators and the Australian-New Zealand Intensive Care Society Clinical Trials Group. Adjunctive Glucocorticoid Therapy in Patients with Septic Shock. N Engl J Med. 2018 Mar 1;378(9):797-808. doi: 10.1056/NEJMoa1705835. Epub 2018 Jan 19.

Reference Type DERIVED
PMID: 29347874 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

GI-CCT372273

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Septic Shock em Steroids
NCT01047670 UNKNOWN PHASE2/PHASE3
Adrenal Insufficiency in Septic Shock
NCT00842933 TERMINATED PHASE4
Triple Therapy in Septic Shock Patients
NCT04508946 COMPLETED PHASE3