ADjunctive coRticosteroid trEatment iN criticAlly ilL Patients With Septic Shock

NCT01448109 | Completed Phase 4 DMC

• 1 other identifier: GI-CCT372273
• Study Type: interventional
• Target: 3,800
• Locations: 5 countries
• Sites: 70

Brief 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.

Conditions

Septic Shock

Keywords

Sepsis; Corticosteroid

Outcome Measures

Primary Outcomes (1)

• All cause mortality at 90 days after randomisation

  90 days after randomisation

Secondary Outcomes (10)

• All-cause mortality at 28 days and 6 months after randomisation

  28 days and 6 months after randomisation

• Time to resolution of shock

  MAP goal for >24 hours without vasopressors or inotropes. Up to 90 days after randomisation.

• Recurrence of shock

  Up to90 days after randomisation

• Duration of ICU stay

  Up to 90 days after randomisation

• Duration of hospital stay

  Up to 90 days after randomisation

Study Arms (2)

Hydrocortisone

ACTIVE COMPARATOR

Drug: Hydrocortisone

Sterile air filled vial

PLACEBO COMPARATOR

Drug: Sterile air filled vial

Interventions

Hydrocortisone 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.

Also known as: Solu-Cortef

Hydrocortisone

Sterile air filled vial 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

Sterile air filled vial

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 years or older
• 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.
• Being treated with mechanical ventilation at the time of randomisation
• 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
• Administration of vasopressors or inotropes for = 4 hours and present at time of randomisation.

You may not qualify if:

• Clinician expects to prescribe systemic corticosteroids for an indication other than septic shock (not including nebulised or inhaled corticosteroid)
• Patients treated with etomidate
• Patients receiving treatment with Amphotericin B for systemic fungal infections at time of randomisation
• Patients with documented cerebral malaria at the time of randomisation
• Patients with documented strongyloides infection at the time of randomisation
• 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
• Death from underlying disease is likely within 90 days
• Patient has been previously enrolled in the ADRENAL study.

Sponsors & Collaborators

• The George Institute: lead
• National Health and Medical Research Council, Australia: collaborator
• Australian and New Zealand Intensive Care Society Clinical Trials Group: collaborator

Study Sites (70)

Blacktown Hospital

Blacktown, New South Wales, 2148, Australia

Location

Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

Location

St Vincent's Hospital

Darlinghurst, New South Wales, 2010, Australia

Location

Gosford Hospital

Gosford, New South Wales, 2250, Australia

Location

St George Hospital

Kogarah, New South Wales, 2217, Australia

Location

Liverpool Hospital

Liverpool, New South Wales, 1871, Australia

Location

John Hunter Hospital

Newcastle, New South Wales, 2305, Australia

Location

Nepean Hospital

Penrith, New South Wales, 2747, Australia

Location

Prince of Wales Hospital

Randwick, New South Wales, 2031, Australia

Location

Royal North Shore Hospital

St Leonards, New South Wales, 2065, Australia

Location

The George Institute for Global Health

Sydney, New South Wales, 2000, Australia

Location

Tamworth Rural Referral Hospital

Tamworth, New South Wales, 2340, Australia

Location

Tweed Heads District Hospital

Tweed Heads, New South Wales, 2485, Australia

Location

Calvary Mater Hospital (Newcastle)

Waratah, New South Wales, 2298, Australia

Location

Wollongong Hospital

Wollongong, New South Wales, 2521, Australia

Location

Royal Darwin Hospital

Darwin, Northern Territory, 0810, Australia

Location

Wesley Hospital

Auchenflower, Queensland, 4066, Australia

Location

Prince Charles Hospital

Brisbane, Queensland, 4032, Australia

Location

Mater Health Services

Brisbane, Queensland, 4101, Australia

Location

Gold Coast University Hospital

Gold Coast, Queensland, 4215, Australia

Location

Royal Brisbane and Women's Hospital

Herston, Queensland, 4029, Australia

Location

Ipswich Hospital

Ipswich, Queensland, 4307, Australia

Location

Logan Hospital

Logan City, Queensland, 4131, Australia

Location

Mackay Base Hospital

Mackay, Queensland, 4740, Australia

Location

Nambour Hospital

Nambour, Queensland, 4560, Australia

Location

Redcliffe Hospital

Redcliffe, Queensland, 4020, Australia

Location

Toowoomba Hospital

Toowoomba, Queensland, 4350, Australia

Location

Townsville Hospital

Townsville, Queensland, 4814, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Lyell McEwin Hospital

Elizabeth Vale, South Australia, 5112, Australia

Location

The Queen Elizabeth Hospital

Woodville South, South Australia, 5011, Australia

Location

Royal Hobart Hospital

Hobart, Tasmania, 7000, Australia

Location

Bendigo Hospital

Bendigo, Victoria, 3550, Australia

Location

Monash Medical Centre

Clayton, Victoria, 3168, Australia

Location

Northern Hospital

Epping, Victoria, 3076, Australia

Location

St Vincent's Hospital (Melbourne)

Fitzroy, Victoria, 3065, Australia

Location

Footscray Hospital

Footscray, Victoria, 3011, Australia

Location

Geelong Hospital (Barwon Health)

Geelong, Victoria, 3220, Australia

Location

Austin Hospital

Heidelberg, Victoria, 3084, Australia

Location

Royal Melbourne Hospital

Parkville, Victoria, 3050, Australia

Location

Sunshine Hospital

St Albans, Victoria, 3021, Australia

Location

Fremantle Hospital

Fremantle, Western Australia, 6959, Australia

Location

Fiona Stanley Hospital

Murdoch, Western Australia, 6150, Australia

Location

Royal Perth Hospital

Perth, Western Australia, 6000, Australia

Location

St John of God Hospital-Murdoch

Perth, Western Australia, 6150, Australia

Location

Rigshospitalet

Copenhagen, 2100, Denmark

Location

North Shore Hospital

North Shore, Auckland, 0622, New Zealand

Location

Waikato Hospital

Hamilton, NZ, 3240, New Zealand

Location

Auckland City Hospital (CVICU)

Auckland, 1142, New Zealand

Location

Auckland City Hospital (DCCM)

Auckland, 1142, New Zealand

Location

Middlemore Hospital

Auckland, 1640, New Zealand

Location

Christchurch Hospital

Christchurch, 8011, New Zealand

Location

Tauranga Hospital

Tauranga, 3110, New Zealand

Location

Wellington Hospital

Wellington, 6011, New Zealand

Location

King Abdulaziz Medical City

Riyadh, 11426, Saudi Arabia

Location

King Khalid University Hospital, King Saud University

Riyadh, 11472, Saudi Arabia

Location

King Fahad Medical City

Riyadh, 11525, Saudi Arabia

Location

Bristol Royal Infirmary

Bristol, England, BS2 8HW, United Kingdom

Location

Ashford & St.Peter's NHS Foundation Trust

Chertsey, England, KT16 0PZ, United Kingdom

Location

Queen Alexandra Hospital (Portsmouth)

Cosham, England, PO63LY, United Kingdom

Location

Queen Elizabeth Hospital Birmingham

Edgbaston, England, B15 2TH, United Kingdom

Location

Royal Surrey County Hospital

Guildford, England, GU2 7XX, United Kingdom

Location

Lewisham Healthcare NHS Trust

London, England, SE 13 6LH, United Kingdom

Location

Guy's and St Thomas' HNS Foundation Trust

London, England, SE1 9RT, United Kingdom

Location

King's College Hospital NHS Foundation Trust

London, England, SE5 9RS, United Kingdom

Location

St Georges Healthcare NHS Trust

London, England, SW17 0QH, United Kingdom

Location

Freeman Hospital

Newcastle upon Tyne, England, NE7 7DN, United Kingdom

Location

University Hospital Southampton

Southampton, England, S016 6YD, United Kingdom

Location

Royal Gwent Hospital

Newport, Wales, NP20 2UB, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 38239409 DERIVED

• 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.

  PMID: 37853343 DERIVED

• 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.

  PMID: 29347874 DERIVED

MeSH Terms

Conditions

Shock, Septic; Sepsis

Interventions

Hydrocortisone; hydrocortisone hemisuccinate

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids

Study Officials

• Balasubramanian Venkatesh

  The George Institute

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2011
• First Posted: October 7, 2011
• Study Start: June 13, 2012
• Primary Completion: October 22, 2017
• Study Completion: November 20, 2017
• Last Updated: December 12, 2017

Record last verified: 2017-09

Locations

NZ (8); SA (3); DK (1); GB (12); AU (46)