Critical Illness and Mechanical Ventilation Clinical Trial
— SPICE III RCTOfficial title:
Early Goal-Directed Sedation Compared With Standard Care in Mechanically Ventilated Critically Ill Patients: a Prospective Multicentre Randomised Controlled Trial
| Verified date | April 2019 |
| Source | Australian and New Zealand Intensive Care Research Centre |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
The Use of sedative drugs in intensive care is widespread. A cohort study conducted in
Australia and New Zealand in 2010 revealed a high prevalence of deep sedation within the
first 48 hours of mechanical ventilation which was independently linked to prolonged
ventilation, hospital and 180 days mortality. Clinical practice is moving towards the use of
lighter levels of sedation. Recent RCTs in Europe (JAMA 2012) and previous RCTs (JAMA 2009)
supports growing evidence that dexmedetomidine facilitates rousable sedation, shortens
ventilation time and attenuates delirium when compared to midazolam and propofol.
The investigators confirmed in a pilot study the feasibility, efficacy and safety of a
process of care known as Early Goal Directed Sedation (EGDS) that delivers:
1. Early randomization after intubation or arrival in the ICU (intubated).
2. Early Adequate analgesia after randomization.
3. Goal directed sedation titrated to achieve light sedation.
4. Dexmedetomidine based algorithm as the primary sedative agent with avoidance of
benzodiazepines.
The aim of this study is to assess the effectiveness of Early Goal Directed Sedation when
compared to standard care sedation in critically ill patients.
The study hypothesis is that Early Goal-Directed Sedation (EGDS), compared to standard care
sedation, reduces 90-day all-cause mortality in critically ill patients who require
mechanical ventilation.
| Status | Completed |
| Enrollment | 4000 |
| Est. completion date | December 2018 |
| Est. primary completion date | August 2018 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility |
Inclusion Criteria: - Patient has been intubated and is receiving mechanical ventilation - The treating clinician expects that the patient will remain intubated until the day after tomorrow (unlikely to be extubated the following day). - The patient requires immediate ongoing sedative medication for comfort, safety, and to facilitate the delivery of life support measures. Exclusion Criteria: - Age less than 18 years - Patient is pregnant and/or lactating - Has been intubated (excluding time spent intubated within an operating theatre or transport) for greater than 12 hours in an intensive care unit. - Proven or suspected acute primary brain lesion such as traumatic brain injury, intracranial haemorrhage, stroke, or hypoxic brain injury. - Proven or suspected spinal cord injury or other pathology that may result in permanent or prolonged weakness. - Admission as a consequence of a suspected or proven drug overdose or burns. - Administration of ongoing neuromuscular blockade. - A mean arterial blood (MAP) pressure that is less than 50 mmHg despite adequate resuscitation and vasopressor therapy at time of randomisation - Heart rate less than 55 beats per minute unless the patient is being treated with a beta-blocker or a high grade atrio-ventricular block in the absence of a functioning pacemaker. - Known sensitivity to any of the study medications or the constituents of propofol (egg, soya or peanut protein) - Acute fulminant hepatic failure - Patient has been receiving full time residential nursing care. - Death is deemed to be imminent or inevitable during this admission and either the attending physician, patient or substitute decision maker is not committed to active treatment. - Patient has an underlying disease that makes survival to 90 days unlikely - Patient has been previously enrolled in the SPICE study. |
| Country | Name | City | State |
|---|---|---|---|
| Australia | Albury Hospital | Albury | New South Wales |
| Australia | Bendigo Hospital | Bendigo | Victoria |
| Australia | Blacktown Hospital | Blacktown | New South Wales |
| Australia | Sunshine Coast Hospital (Nambour Hospital) | Buderim | Queensland |
| Australia | Dandenong Hospital | Dandenong | Victoria |
| Australia | St Vincent's Hospital Sydney | Darlinghurst | New South Wales |
| Australia | Lyell McEwan Hospital | Elizabeth Vale | South Australia |
| Australia | Northern Hospital | Epping | Victoria |
| Australia | Geelong Hospital | Geelong | Victoria |
| Australia | Gosford Hospital | Gosford | New South Wales |
| Australia | Austin Hospital | Heidelberg | Victoria |
| Australia | Royal Brisbane and Women's hospital | Herston | Queensland |
| Australia | Royal Hobart Hospital | Hobart | Tasmania |
| Australia | Hornsby Ku-ring-gai Hospital | Hornsby | New South Wales |
| Australia | Launceston General Hospital | Launceston | Tasmania |
| Australia | Monash Medical Centre | Melbourne | Victoria |
| Australia | Royal Melbourne Hospital | Melbourne | Victoria |
| Australia | Nepean Hospital | Penrith | New South Wales |
| Australia | St John Of God, Subiaco | Perth | Western Australia |
| Australia | Redcliffe Hospital | Redcliffe | Queensland |
| Australia | Central Gippsland Health Service | Sale | Victoria |
| Australia | Gold Coast Hospital & Health Service | Southport | Queensland |
| Australia | Royal North Shore Hospital | St. Leonards | New South Wales |
| Australia | Prince of Wales Hospital | Sydney | New South Wales |
| Australia | Royal Darwin Hospital | Tiwi | Northern Territory |
| Australia | Toowoomba Hospital | Toowoomba | Queensland |
| Australia | Knox Private Hospital | Wantirna | Victoria |
| Australia | Westmead Hospital | Westmead | New South Wales |
| Australia | Princess Alexandra Hospital | Woolloongabba | Queensland |
| Ireland | St James's University Hospital | Dublin | Dublin 8 |
| Ireland | St Vincent's University Hospital | Dublin | Dublin 4 |
| Italy | Ospedale San Raffaele | Milan | |
| Malaysia | Penang General Hospital | George Town | Pulau Pinang |
| Malaysia | Raja Perempuan Zainab II Hospital | Kota Bharu | Kelantan |
| Malaysia | Universiti Sains Malaysia Hospital | Kota Bharu | Kelantan |
| Malaysia | Queen Elizabeth Hospital | Kota Kinabalu | Sabah |
| Malaysia | Institut Jantung Negara | Kuala Lumpur | |
| Malaysia | Kuala Lumpar General Hospital | Kuala Lumpur | |
| Malaysia | University Malaya Medical Center | Kuala Lumpur | |
| Malaysia | Sarawak General Hospital | Kuching | Sarawak |
| Malaysia | Melaka General Hospital | Melaka | |
| New Zealand | Christchurch Hospital | Addington | Christchurch |
| New Zealand | Auckland City hospital | Auckland | |
| New Zealand | Dunedin Hospital | Dunedin | |
| New Zealand | Auckland City Hospital CVICU | Grafton | Auckland |
| New Zealand | Wellington Hospital | Newtown | Wellington |
| New Zealand | Middlemore Hospital | Otahuhu | Auckland |
| New Zealand | Rotorua Hospital | Rotorua | |
| New Zealand | North Shore Hospital | Takapuna | North Shore City |
| Saudi Arabia | King Abdulaziz Medical City | Riyadh | |
| Saudi Arabia | King Saud Medical City | Riyadh | |
| Saudi Arabia | Prince Sultan Military Medical City | Riyadh | |
| Switzerland | Inselspital University Hospital Bern | Bern | |
| United Kingdom | Queen Elizabeth Hospital, Birmingham | Birmingham | |
| United Kingdom | Royal Bournemouth Hospital | Bournemouth | |
| United Kingdom | University Hospitals Bristol | Bristol | |
| United Kingdom | Kings College Hospital | Brixton | London |
| United Kingdom | University Hospital of Wales | Cardiff | |
| United Kingdom | University Hospital of Coventry and Warwick | Coventry | |
| United Kingdom | Derriford Hospital | Crownhill | Plymouth |
| United Kingdom | Dorset County Hospital | Dorchester | |
| United Kingdom | Royal Infirmary of Edinburgh | Edinburgh | |
| United Kingdom | Western General Hospital | Edinburgh | |
| United Kingdom | University Hospital of North Tees | Hardwick | Stockton-on-Tees |
| United Kingdom | Freeman Hospital | High Heaton | Newcastle Upon Tyne |
| United Kingdom | Queen Elizabeth Hospital King's Lynn | King's Lynn | Norfolk |
| United Kingdom | Royal Liverpool University Hospital | Liverpool | |
| United Kingdom | St George's Hospital | London | |
| United Kingdom | St Thomas Hospital | London | |
| United Kingdom | University College Hospital | London | |
| United Kingdom | Altnagelvin Hospital | Londonderry | |
| United Kingdom | Royal Victoria Infirmary | Newcastle Upon Tyne | |
| United Kingdom | Princess Royal University Hospital | Orpington | |
| United Kingdom | Royal Berkshire Hospital | Reading |
| Lead Sponsor | Collaborator |
|---|---|
| Australian and New Zealand Intensive Care Research Centre | National Health and Medical Research Council, Australia |
Australia, Ireland, Italy, Malaysia, New Zealand, Saudi Arabia, Switzerland, United Kingdom,
Shehabi Y, Bellomo R, Reade MC, Bailey M, Bass F, Howe B, McArthur C, Seppelt IM, Webb S, Weisbrodt L; Sedation Practice in Intensive Care Evaluation (SPICE) Study Investigators; ANZICS Clinical Trials Group. Early intensive care sedation predicts long-term mortality in ventilated critically ill patients. Am J Respir Crit Care Med. 2012 Oct 15;186(8):724-31. doi: 10.1164/rccm.201203-0522OC. Epub 2012 Aug 2. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Mortality | Day 90 post randomisation | ||
| Secondary | Ventilation free days | at 28 days following randomisation | ||
| Secondary | Proportion of RASS measurements in target range | up to day 28 | ||
| Secondary | Incidence and duration of delirium measured by delirium free days | up to 28 days | ||
| Secondary | Length of ICU stay | up to 180 days | ||
| Secondary | Proportion of patients who receive a tracheostomy Proportion of patients who require: re-intubation, physical restraints,or unplanned extubation, | up to day 28 | ||
| Secondary | Cumulative dose of midazolam, propofol, dexmedetomidine, fentanyl, and morphine | up to 28 days | ||
| Secondary | Duration of treatment with midazolam, propofol, dexmedetomidine, fentanyl, and morphine | up to 28 days | ||
| Secondary | Mortality at hospital discharge | at hospital discharge up to 180 days | ||
| Secondary | Length of hospital stay | up to 180 days | ||
| Secondary | Readmission to ICU | at 90 days | ||
| Secondary | EQ-5D questionnaire | at 180 days | ||
| Secondary | Cognitive function | at 180 days | ||
| Secondary | Mortality at ICU discharge | up to 180 days | ||
| Secondary | Full time institutional dependency at 180 days | up to 180 days | ||
| Secondary | Discharge destination | up to 180 days |