Staphylococcus Aureus Network Adaptive Platform Trial

Phase 4

Recruiting

Conditions: Staphylococcus Aureus Bacteremia

Interventions: Radiation: Whole body FDG PET/CT Imaging
Drug: Penicillin
Other: Effectiveness of early switch to oral antibiotics
Drug: Cefazolin
Drug: Clindamycin
Drug: Vancomycin

Registration Number: NCT05137119

Lead Sponsor: University of Melbourne

Brief Summary: The Staphylococcus aureus Network Adaptive Platform (SNAP) trial is an International Multi-Centered Randomised Adaptive Platform Clinical Trial to evaluate a range of interventions to reduce mortality for patients with Staphylococcus Aureus bacteraemia (SAB).

Detailed Description: Infection of the bloodstream with the bacterium Staphylococcus aureus (Staphylococcus aureus bacteraemia, SAB) is a serious infection that results in 15-30% of affected patients dying within three months of acquiring the infection. Treatment of this infection requires patients to be hospitalised, treated with prolonged antibiotics through an intravenous line, and carefully examined for the occurrence of complications associated with this condition. At present, there are many treatment options in current use, with no clear agreement as to which of these is best. The SNAP trial aims to identify which treatment options for SAB results in the fewest patients dying within the first 90 days after an infection.

In contrast to a conventional clinical trial, the SNAP trial will examine multiple different treatment options at once. Patients will be randomly assigned to different concurrent treatment options currently considered acceptable in routine medical care, but as the trial progresses, more patients will be assigned to treatments that appear to have better outcomes than those with worse outcomes. The trial will adapt to accumulating trial evidence, on a regular basis, by removing treatment options found to be inferior, incorporating new treatment options, and ensuring that all patients in the trial receive the best treatments once they have been identified. Over time, we hope to determine the best combination of treatment options for patients with SAB.

The SNAP Trial infrastructure will also support a number of sub-studies. A list of all active sub-studies can be found on the SNAP website: https://www.snaptrial.com.au/substudies.

Recruitment & Eligibility

Status: RECRUITING

Sex: All

Target Recruitment: 8000

Inclusion Criteria

Patients must fulfil all of the following criteria to be eligible to enter the SNAP trial:

Staphylococcus aureus complex grown from ≥1 blood culture
Admitted to a participating hospital at the time of eligibility assessment

PLATFORM

Exclusion Criteria

Potentially eligible participants meeting any of the following criteria at the time of eligibility assessment for platform entry will be excluded from the trial:

Time of anticipated platform entry is greater than 72 hours post collection of the index blood culture. Where the time of culture collection is not recorded, the time of laboratory registration of the sample will be used as an alternative
Polymicrobial bacteraemia, defined as more than one organism (at species level) in the index blood cultures OR in any subsequent blood culture reported between the collection of the index blood culture and platform eligibility assessment, excluding those organisms judged to be contaminants by either the microbiology laboratory or treating clinician.
Known previous participation in the randomised SNAP platform
Known positive blood culture for S. aureus (of the same silo: PSSA, MSSA or MRSA) between 72 hours and 180 days prior to the time of eligibility assessment
Treating team deems enrolment in the study is not in the best interest of the patient
Treating team believes that death is imminent and inevitable
Patient is for end-of-life care and antibiotic treatment is considered not appropriate
Patient <18 years of age and paediatric recruitment not approved at recruiting site
Patient has died since the collection of the index blood culture

To be included in any of the following DOMAINS the participant must met eligible for the PLATFORM (as listed above)

ADJUNCTIVE TREATMENT DOMAIN

Inclusion Criteria:

All participants that met the PLATFORM eligible are eligible to be included in this domain unless they meet any of the following exclusions listed.
Patients are eligible for this domain regardless of S. aureus susceptibility testing results to clindamycin.

Exclusion criteria:
Previous type 1 hypersensitivity reaction to lincosamides 2. Currently receiving clindamycin (lincomycin) or linezolid which cannot be ceased or substituted 3. Necrotising fasciitis 4. Current C. difficile associated diarrhoea (any severity) 5. Current severe diarrhoea from any cause (defined as Grade 3 or higher) 5. Known CDAD (C.Difficile Associated Diarrhoea) in the past 3 months, or CDAD relapse in the past 12 months 6. At the time of domain eligibility assessment, more than 4 hours has elapsed since platform entry 7. Treating clinician deems enrolment in this domain is not in the best interest of the patient

PSSA, MSSA TREATMENT DOMAIN (backbone)

Inclusion Criteria:

For PSSA silo: Index blood culture is penicillin-susceptible as per phenotypic disc testing with EUCAST (a P1 disc diffusion with a feathered zone >=26mm) OR CLSI (a P10 disc diffusion) defined criteria
For MSSA silo: Index blood culture isolate is methicillin-susceptible but penicillin resistant

Exclusion Criteria (PSSA & MSSA):

>72 hours have elapsed since the collection of the index blood culture (i.e. the time of collection of the first positive blood culture from the patient during this episode)
History of type I hypersensitivity reaction (i.e. anaphylaxis or angioedema) to any penicillin or cephalosporin
History of severe delayed reaction (e.g. allergic interstitial nephritis, cutaneous vasculitis, Stevens-Johnson, DRESS, etc.) to any penicillin or cephalosporin
PSSA silo: Non-severe rash to any penicillin (unless patient has been subsequently de-labelled; this criteria does not include criteria 2 and 3 above), or MSSA silo: Non-severe rash to cefazolin or any penicillin (unless patient has been subsequently de-labelled) (Nausea, diarrhoea, headache, and other non-specific symptoms are NOT allergies, they are drug intolerance, and they are not exclusion criteria. Similarly, a vague history of an allergy of unclear nature, or a family history of allergy are not exclusions.)
Treating team deems enrolment in this domain is not in the best interest of the patient
Currently receiving maintenance dialysis (haemodialysis or peritoneal dialysis) (Acute renal replacement therapy (including CRRT, haemodialysis or peritoneal dialysis) are not exclusions. Such patients are eligible as long as appropriate vascular access is available or can be arranged.)
Polymicrobial bacteraemia (defined as more than one organism [at species level] in blood cultures, excluding those organisms judged to be contaminants by either the microbiology laboratory or treating clinician) reported between collection of the index blood culture and backbone domain eligibility assessment
Patient currently being treated with a systemic antibacterial agent that cannot be ceased or substituted for interventions allocated within the platform (unless antibiotic is listed in Table 1 of the DSA, which specifies allowed antibiotics with limited absorption from the gastrointestinal tract or negligible antimicrobial activity against S. aureus)

MRSA TREATMENT DOMAIN (backbone)

Inclusion Criteria:

MRSA confirmed microbiologically

Exclusion Criteria:

Time to allocation reveal is >72 hours from time of index blood culture collection
Severe allergy to any beta-lactam (including cefazolin) Immediate severe allergy: Anaphylaxis/angioedema Severe delayed allergy: Severe cutaneous adverse reaction (SCAR; including Steven Johnson Syndrome, Toxic Epidermal Necrolysis, Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) and acute generalised exanthematous pustulosis (AGEP)), severe drug induced liver injury, proven allergic interstitial nephritis, immune-mediated haemolytic anaemia and other severe cytopenia.
Non-severe rash to cefazolin Nausea, diarrhoea, headache and other non-specific symptoms are NOT allergies, they are drug intolerance, and they are not exclusion criteria. Similarly, a vague history of an allergy of unclear nature, or a family history of allergy are not exclusions.)
Severe allergy or non-severe rash to both vancomycin AND daptomycin Vancomycin infusion reaction (formerly known as "red man syndrome") is due to direct histamine release and is not generally an allergy, and therefore is not considered an exclusion.
Treating team deems enrolment in the domain is not in the best interest of the patient 6. Polymicrobial bacteraemia (defined as more than one organism [at species level] in blood cultures, excluding those organisms judged to be contaminants by either the microbiology laboratory or treating clinician) reported between collection of the index blood culture and backbone domain eligibility assessment.
Patient currently being treated with a systemic antibacterial agent that cannot be ceased or substituted for interventions allocated within the platform (unless antibiotic is listed in Table 1 of the DSA, which specifies allowed antibiotics with limited absorption from the gastrointestinal tract or negligible antimicrobial activity against S. aureus)

EARLY ORAL SWITCH DOMAIN

Inclusion Criteria:

Day 7 (+/- 2 days):

Clearance of SAB by platform Day 2: blood cultures negative for S. aureus from platform Day 2 onwards AND no known subsequent positive blood cultures
Afebrile (<37.8°C) for the past 72 hours (at time of judging eligibility)
Primary focus is either line related (either central or peripheral IV cannula) or skin and soft tissue, AND source control achieved (for 'line-related' this means line removed; for 'skin and soft tissue' means site PI considers source control to have been achieved and any abscess more than 2cm diameter has been drained)
No evidence of metastatic foci (on clinical or radiological examination, but radiological imaging is not required to exclude metastatic foci if not clinically indicated)

Day 14 (+/- 2 days):

Clearance of SAB by platform Day 5: blood cultures negative for S. aureus from platform Day 5 (+/-1 day) AND no known subsequent positive blood cultures. If the most recent blood culture from Day 2-4 is negative for S. aureus, blood cultures do not need to be repeated on Day 5 to fulfil eligibility criteria (Day 5 blood cultures will be assumed to be negative in this situation)
Afebrile (<37.8°C) for the past 72 hours (at time of judging eligibility)
Site Principal Investigator has determined that source control is adequate

Exclusion Criteria:

When judging eligibility at platform Day 7 (+/- 2 days) and at Day 14 (+/- 2 days), exclusion criteria are:

Adherence to oral agents unlikely (as judged by site PI in consultation with the treating team)
Unreliable gastrointestinal absorption (e.g. vomiting, diarrhoea, nil by mouth, anatomical reasons)
There are no appropriate oral antibiotics due to contraindications, drug availability, or antibiotic resistance
Ongoing IV therapy unsuitable e.g. no IV access
Clinician deems not appropriate for early oral switch
Patient no longer willing to participate in domain In the lead-up to judging eligibility, it may be helpful to discuss with the patient the potential for continued IV treatment versus oral switch, to allow hospital discharge planning
Clinical team deems that sufficient duration of antibiotic therapy has already been provided

Exclusions when judging eligibility for early oral switch at trial Day 7 (+/- 2 days):

Presence of prosthetic cardiac valve, pacemaker or other intracardiac implant
Presence of intravascular clot, graft, or other intravascular prosthetic material Intravascular clot excludes superficial peripheral IV line-related thrombophlebitis. Intravascular prosthetic material excludes coronary artery stents)
Intravascular/intracardiac infections (e.g. endocarditis, mycotic aneurysm)
Presence of other intracardiac abnormalities felt to put patient at increased risk of endocarditis (e.g., bicuspid aortic valve)

PET/CT DOMAIN

Inclusion Criteria:

PET/CT participating site
Patient is accessible for PET/CT - a patient is considered accessible if the site team are able to access the participant medical records, arrange for a PET/CT scan for the patient, and discuss this domain with the patient and their treating healthcare providers.

Exclusion Criteria:

Pregnant - patients of childbearing potential should be assessed for pregnancy status and a pregnancy test performed (if not performed within the past 10 days)
Currently breastfeeding
< 18 years of age
Patient has had PET/CT in the past 7 days
Patient needs PET/CT in the next 7 days (in the opinion of the clinical team, at the time of eligibility assessment)
Clinically unstable for PET/CT (as judged by the treating clinical team, taking into account need for organ support (including inotropes) and capacity to lie flat for the PET/CT)
Contraindication to PET/CT (e.g., claustrophobia, persistently elevated blood sugar levels [>12.5mmol/L] that cannot be corrected).
Patient no longer willing to participate in the domain - in the days leading up to judging eligibility, it may be helpful to discuss with the patient the potential for PET/CT vs no PET/CT to allow imaging planning
Clinician deems participation in this domain is not in the patient's best interests

Study & Design

Study Type: INTERVENTIONAL

Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
PET/CT scan at trial day 7 (+/- 2 days) if eligible	Whole body FDG PET/CT Imaging	Participant will receive a PET/CT scan at Day 5-12, in addition to their allocated treatment interventions. Participants eligibility is assessed at Day 7 (+/- 2 days) if eligible will be randomised. If eligibility is not met then participant is excluded from this domain.
Penicillin-susceptible staphylococcus aureus (PSSA) - Interventional Arm (backbone therapy)	Penicillin	Benzylpenicillin - Interventional Arm Intravenous benzylpenicillin 1.8g (3 million units) every 4 or 6 hours. The minimum protocol duration of allocated study treatment is 14 days for those not allocated to early oral switch, and 5 days for those allocated to early oral switch. For patients with critical illness the intravenous benzylpenicillin administration doses will be adjusted.
Switch to oral antibiotics at trial day 7 (+/- 2 days) or Day 14 (+/- 2 days) if eligible.	Effectiveness of early switch to oral antibiotics	Switch from intravenous backbone antibiotic for MRSA or MSSA or PSSA to oral antibiotics at the treating clinicians discretion on trial Day 7 (+/- 2 days) or trial Day 14 (+/- 2 days). Participants eligibility is assessed at Day 7 (+/- 2 days). If eligible will be randomised, if not eligible then eligibility will be assessed again at Day 14 (+/- 2 days). If eligibility is not met at day 14 then participant is excluded from this domain.
Methicillin-resistant staphylococcus aureus (MRSA) - Standard + B-Lactam Arm (backbone therapy)	Cefazolin	Vancomycin or Daptomycin (Standard Therapy) + Beta-Lactam (β-lactam) Arm In addition to standard treatment an intravenous β-lactam will be added for the first 7 calendar days following randomisation (day 1 being the day of randomisation - hence patients will receive 6-7 days of β-lactam). This β-lactam will be intravenous cefazolin 2g every 8 hours. For patients with renal impairment the intravenous cefazolin administration doses will be adjusted.
Methicillin-resistant staphylococcus aureus (MRSA) - Standard + B-Lactam Arm (backbone therapy)	Vancomycin	Vancomycin or Daptomycin (Standard Therapy) + Beta-Lactam (β-lactam) Arm In addition to standard treatment an intravenous β-lactam will be added for the first 7 calendar days following randomisation (day 1 being the day of randomisation - hence patients will receive 6-7 days of β-lactam). This β-lactam will be intravenous cefazolin 2g every 8 hours. For patients with renal impairment the intravenous cefazolin administration doses will be adjusted.
Methicillin-susceptible staphylococcus aureus (MSSA) - Interventional Arm (backbone therapy)	Cefazolin	Cefazolin - Interventional Arm Intravenous cefazolin 2g every 6 or 8 hours. The minimum protocol duration of allocated study treatment is 14 days for those not allocated to early oral switch, and 5 days for those allocated to early oral switch. For patients with renal impairment or critical illness the intravenous cefazolin administration dose will be adjusted.
Adjunctive treatment in combination with MRSA or MSSA or PSSA backbone therapy arm	Clindamycin	Adjunctive therapy + backbone therapy arm for MRSA or MSSA or PSSA Intravenous clindamycin (or lincomycin) 600mg every 8 hours from platform day 1 to day 5. No dosage adjustment is needed to renal impairment.

Primary Outcome Measures

Name	Time	Method
All-cause mortality at 90 days after platform entry	From randomisation (day 1) until day 90	The primary endpoint for all cells and domains will be all-cause mortality at 90 days after platform entry. The primary endpoint will be determined through a search of hospital databases for a record of a participant's death, or follow-up contact with the participant's community healthcare provider, or follow-up contact with the patient or their nominated carer, or linkage with death registries.

Secondary Outcome Measures

Name	Time	Method
All-cause mortality at 14, 28 and 42 days after platform entry	From randomisation (day 1) until day 14, 28, and 42	Determined through a search of hospital databases for a record of a participant's death, or follow-up contact with the participant's community healthcare provider, or follow-up contact with the patient or their nominated carer, or linkage with death registries.
Duration of survival censored at 90 days after platform entry	From randomisation (day 1) until day 90	Determined through a search of hospital databases for a record of a participant's death, or follow-up contact with the participant's community healthcare provider, or follow-up contact with the patient or their nominated carer, or linkage with death registries.
Number of antibiotic days (IV and/or oral/enteral)	From randomisation (day 1) until day 90	All days on which any antibiotic dose is received should be counted - i.e. we are counting the number of whole or part days on which any antibiotics are received (not the number of defined daily doses of antibiotics). Topical, inhaled or other routes of administration besides IV or oral/enteral should not be counted.
Length of stay of acute index inpatient hospitalisation for those surviving until discharge from acute inpatient facilities (excluding HITH/COPAT/OPAT/rehab).	From randomisation (day 1) until discharge from acute inpatient facilities, truncated at 90 days.	Acute index hospitalisation is defined as continuous hospital admission to one or more acute inpatient facilities for the index episode. This does not include HITH/OPAT/COPAT and stepdown inpatient rehabilitation/post-acute care. It does include admission to acute care hospitals immediately preceding and following those at the enrolling site.
Diagnosis of new foci between 14 and 90 days after platform entry.	From randomisation (day 1) until day 90	The presence of new foci will be determined by the site investigator and can incorporate clinical, radiological, microbiological and pathological findings.
Health economic costs as detailed in the cost utility analysis appendix.	From randomisation (day 1) until day 90	Including hospital length of stay, readmissions, and patient employment status.
Length of stay of total index hospitalisation for those surviving until hospital discharge (including HITH/COPAT/OPAT/rehab)	From randomisation (day 1) to discharge from total index hospitalisation, truncated at 90 days	Total index hospitalisation is defined as continuous hospital admission to one or more inpatient facilities for the index episode, including HITH/OPAT/COPAT and stepdown inpatient rehabilitation/post-acute care (if continuous with the initial inpatient admission). It includes admission to acute care hospitals immediately preceding and following those at the enrolling site.
Microbiological treatment failure defined as positive sterile site culture for S. aureus [of the same silo as the index isolate between 14 and 90 days after platform entry).	From randomisation (day 1) until day 90	A sterile site means any sites deep to the skin and skin structures, including deep visceral and musculoskeletal abscesses that have been obtained in a sterile manner.
C. difficile diarrhoea as determined by a clinical laboratory in the 90 days following platform entry for participants ≥2 years of age.	From randomisation (day 1) until day 90	This means a stool submitted to a clinical laboratory has tested positive for C. difficile toxin or toxin gene.
Proportion of participants who have returned to their usual level of function at day 90.	From randomisation (day 1) until day 90	Determined by whether the modified functional bloodstream infection score (FBIS) remained the same or improved between baseline and 90 days after platform entry.
Desirability of outcome ranking 1 (modified Antibiotic Resistance Leadership Group version)	From randomisation (day 1) until day 90	unable to insert modified ARLG table
Desirability of outcome ranking 2 (SNAP version)	From randomisation (day 1) until day 90	unable to insert SNAP DOOR table
Time to being discharged alive from the total index hospitalisation (including HITH/COPAT/OPAT/rehab) truncated at 90 days after platform entry	From randomisation (day 1) to discharge from total index hospitalisation, truncated at 90 days	and all deaths within 90 days will be considered '90 days'
Number of participants with Serious adverse reactions (SARs) in the 90 days following platform entry	From randomisation (day 1) until day 90	SARs defined only as events that are attributable to one or more study interventions
Days alive and free of antibiotics	From randomisation (day 1) until day 90	All antibiotics should be included, not only those intended for treatment of S. aureus bacteraemia. It also includes prophylactic dose antibiotics (e.g., prophylactic dose trimethoprim-sulfamethoxazole)

Trial Locations

Locations (149): Cairns Hospital
🇦🇺
Cairns, Queensland, Australia
Hôpital Régional de Saint Jérôme
🇨🇦
Saint-Jérôme, Quebec, Canada
Jeroen Bosch Hospital
🇳🇱
's-Hertogenbosch, Netherlands
Middlemore Hospital
🇳🇿
Otahuhu, Auckland, New Zealand
Christchurch Hospital
🇳🇿
Christchurch, Canterbury, New Zealand
Charlotte Maxeke Johannesburg Academic Hospital
🇿🇦
Johannesburg, South Africa
Royal Devon University Healthcare
🇬🇧
Devon, United Kingdom
NHS Grampian
🇬🇧
Aberdeen, United Kingdom
Greater Glasgow and Clyde
🇬🇧
Glasgow, United Kingdom
Lothian Western General
🇬🇧
Edinburgh, United Kingdom
NHS Golden Jubilee
🇬🇧
Glasgow, United Kingdom
Leeds Teaching Hospitals
🇬🇧
Leeds, United Kingdom
Hull University Teaching Hospitals
🇬🇧
Hull, United Kingdom
Great Ormond Street
🇬🇧
London, United Kingdom
University College London Hospitals
🇬🇧
London, United Kingdom
Kings College Hospital
🇬🇧
London, United Kingdom
University Hospital Southampton
🇬🇧
Southampton, United Kingdom
St. Boniface Hospital
🇨🇦
Winnipeg, Manitoba, Canada
Perth Children's Hospital
🇦🇺
Nedlands, Western Australia, Australia
Health Sciences Centre Winnipeg
🇨🇦
Winnipeg, Manitoba, Canada
Royal Perth Hospital
🇦🇺
Perth, Western Australia, Australia
Armadale Hospital
🇦🇺
Perth, Western Australia, Australia
NHS Tayside
🇬🇧
Dundee, United Kingdom
Box Hill Hospital
🇦🇺
Box Hill, Victoria, Australia
Western Health - Footscray, Joan Kirner & Sunshine Hospitals
🇦🇺
Footscray, Victoria, Australia
South Health Campus
🇨🇦
Calgary, Alberta, Canada
University of Alberta Hospital
🇨🇦
Edmonton, Alberta, Canada
Grampians Health
🇦🇺
Ballarat, Victoria, Australia
Frankston Hospital
🇦🇺
Frankston, Victoria, Australia
La Trobe Regional Hospital
🇦🇺
Traralgon, Victoria, Australia
Bendigo Health
🇦🇺
Bendigo, Victoria, Australia
Royal Children's Hospital Melbourne
🇦🇺
Parkville, Victoria, Australia
Richmond Hospital
🇨🇦
Richmond, British Columbia, Canada
Fraser Health Authority - Surrey Memorial Hospital
🇨🇦
Surrey, British Columbia, Canada
CISSS - Hôpital Cité-de-la-Santé Hospital
🇨🇦
Laval, Quebec, Canada
Antonius Ziekenhuis
🇳🇱
Nieuwegein, Netherlands
Foothills Medical Center
🇨🇦
Calgary, Alberta, Canada
Barwon Health - University Hospital Geelong
🇦🇺
Geelong, Victoria, Australia
Royal Melbourne Hospital
🇦🇺
Parkville, Victoria, Australia
UMC Groningen
🇳🇱
Groningen, Netherlands
Eastern Health - Health Sciences Centre (Memorial University)
🇨🇦
Saint John's, Newfoundland and Labrador, Canada
Vancouver General Hospital
🇨🇦
Vancouver, British Columbia, Canada
Eastern Regional Health Authority - St. Clare's Mercy Hospital
🇨🇦
Saint John's, Newfoundland and Labrador, Canada
Sheba Medical Centre
🇮🇱
Ramat Gan, Israel
Radboud University Medical Center
🇳🇱
Nijmegen, Netherlands
Ikazia Ziekenhuis
🇳🇱
Rotterdam, Netherlands
Tan Tock Seng Hospital
🇸🇬
Singapore, Singapore
Royal Prince Alfred Hospital
🇦🇺
Camperdown, New South Wales, Australia
Fiona Stanley Hospital
🇦🇺
Murdoch, Western Australia, Australia
Kingston Health Sciences Centre - Kingston General Hospital
🇨🇦
Kingston, Ontario, Canada
University of Sherbrooke Health Centre - Hospital Fleurimont
🇨🇦
Sherbrooke, Quebec, Canada
Sinai Heath System - Mount Sinai Hospital
🇨🇦
Toronto, Ontario, Canada
Unity Health Toronto - St Joseph's Health Centre
🇨🇦
Toronto, Ontario, Canada
University of Sherbrooke Health Centre - Hotel Dieu
🇨🇦
Sherbrooke, Quebec, Canada
University Health Network - Toronto Western Hospital
🇨🇦
Toronto, Ontario, Canada
Blacktown Hospital
🇦🇺
Blacktown, New South Wales, Australia
Canberra Hospital
🇦🇺
Garran, Australia Capital Territory, Australia
Concord Repatriation and General Hospital
🇦🇺
Concord, New South Wales, Australia
Nepean Hospital
🇦🇺
Kingswood, New South Wales, Australia
Liverpool Hospital
🇦🇺
Liverpool, New South Wales, Australia
John Hunter Children's Hospital
🇦🇺
Newcastle, New South Wales, Australia
John Hunter Hospital
🇦🇺
New Lambton Heights, New South Wales, Australia
Westmead Hospital
🇦🇺
Westmead, New South Wales, Australia
The Children's Hospital at Westmead
🇦🇺
Westmead, New South Wales, Australia
Sydney Children's Hospital
🇦🇺
Randwick, New South Wales, Australia
Sunshine Coast University Hospital
🇦🇺
Birtinya, Queensland, Australia
Royal Brisbane and Women's Hospital
🇦🇺
Herston, Queensland, Australia
Ipswich Hospital
🇦🇺
Ipswich, Queensland, Australia
Logan Hospital
🇦🇺
Meadowbrook, Queensland, Australia
Redcliffe Hospital
🇦🇺
Redcliffe, Queensland, Australia
Gold Coast University Hospital
🇦🇺
Southport, Queensland, Australia
Queensland Children's Hospital
🇦🇺
South Brisbane, Queensland, Australia
Women and Children's Hospital
🇦🇺
North Adelaide, South Australia, Australia
Royal Hobart Hospital
🇦🇺
Hobart, Tasmania, Australia
Launceston Hospital
🇦🇺
Launceston, Tasmania, Australia
Grace Hospital
🇨🇦
Winnipeg, Manitoba, Canada
Monash Children's Hospital
🇦🇺
Clayton, Victoria, Australia
Monash Health - Monash Medical Centre & Jesse McPherson Private Hospital
🇦🇺
Clayton, Victoria, Australia
Austin Hospital
🇦🇺
Heidelberg, Victoria, Australia
Alfred Hospital
🇦🇺
Melbourne, Victoria, Australia
Goulburn Valley Health
🇦🇺
Shepparton, Victoria, Australia
Peter Lougheed Centre
🇨🇦
Calgary, Alberta, Canada
Rockyview Hospital
🇨🇦
Calgary, Alberta, Canada
Toronto East Health Network - Michael Garron Hospital
🇨🇦
East York, Ontario, Canada
Hamilton Health Sciences - Hamilton General Hospital
🇨🇦
Hamilton, Ontario, Canada
London Health Sciences Centre - University Hospital, LHSC
🇨🇦
London, Ontario, Canada
University Health Network - Toronto General Hospital
🇨🇦
East York, Ontario, Canada
Hamilton Health Sciences - Juravinski Hospital
🇨🇦
Hamilton, Ontario, Canada
Niagara Health - Niagara Falls Site
🇨🇦
Niagara Falls, Ontario, Canada
The Ottawa Hospital - Civic Campus
🇨🇦
Ottawa, Ontario, Canada
Sault Area Hospital
🇨🇦
Sault-Sainte-Marie, Ontario, Canada
The Ottawa Hospital - General Campus
🇨🇦
Ottawa, Ontario, Canada
Niagara Health - St. Catharines Site
🇨🇦
St. Catharines, Ontario, Canada
Unity Health - St Michael's Hospital
🇨🇦
Toronto, Ontario, Canada
Sunnybrook Health Sciences Centre
🇨🇦
Toronto, Ontario, Canada
McGill University Health Centre - Montral General Hospital
🇨🇦
Montréal, Quebec, Canada
Jewish General Hospital
🇨🇦
Montréal, Quebec, Canada
Beilinson Hospital
🇮🇱
Petah tikva, Israel
McGill University Health Centre - Royal Victoria Hospital
🇨🇦
Montréal, Quebec, Canada
McGill University Health Centre - Montreal Children's Hospital
🇨🇦
Montréal, Quebec, Canada
Rambam Health Care Campus
🇮🇱
Haifa, Israel
Schneider Hospital
🇮🇱
Petah tikva, Israel
Auckland City Hospital
🇳🇿
Grafton, Auckland, New Zealand
North Shore Hospital
🇳🇿
Takapuna, Auckland, New Zealand
Starship Hospital
🇳🇿
Auckland, New Zealand
Hutt Valley Hospital
🇳🇿
Boulcott, Lower Hutt, New Zealand
Helen Joseph Hospital
🇿🇦
Johannesburg, South Africa
Singapore General Hospital
🇸🇬
Singapore, Singapore
Wellington Hospital
🇳🇿
Newtown, Wellington, New Zealand
Whangarei Hospital
🇳🇿
Whangarei, New Zealand
Tauranga Hospital
🇳🇿
Tauranga, New Zealand
KidzFirst
🇳🇿
Auckland, New Zealand
National University Hospital
🇸🇬
Singapore, Singapore
Waikato Hospital
🇳🇿
Hamilton, New Zealand
Brighton and Sussex University Hospitals
🇬🇧
Brighton, United Kingdom
University Hospitals Birmingham
🇬🇧
Birmingham, United Kingdom
North Bristol
🇬🇧
Bristol, United Kingdom
University Hospitals Bristol and Weston
🇬🇧
Bristol, United Kingdom
Cardiff and Vale University
🇬🇧
Cardiff, United Kingdom
Cambridge University Hospitals
🇬🇧
Cambridge, United Kingdom
Royal Cornwall Hospitals
🇬🇧
Cornwall, United Kingdom
Liverpool University Hospital
🇬🇧
Liverpool, United Kingdom
Guys and St Thomas'
🇬🇧
London, United Kingdom
Manchester University Hospitals
🇬🇧
Manchester, United Kingdom
Barts Health
🇬🇧
London, United Kingdom
Imperial College Healthcare
🇬🇧
London, United Kingdom
Royal Free London
🇬🇧
London, United Kingdom
Whittington Health
🇬🇧
London, United Kingdom
Newcastle Upon Tyne Hospitals
🇬🇧
Newcastle Upon Tyne, United Kingdom
South Tees Hospitals
🇬🇧
South Tees, United Kingdom
Oxford University Hospitals
🇬🇧
Oxford, United Kingdom
Nottingham University Hospitals
🇬🇧
Nottingham, United Kingdom
Swansea Bay University Health Board
🇬🇧
Swansea, United Kingdom
NHS Forth Valley
🇬🇧
Stirling, United Kingdom
Sheffield Teaching Hospitals
🇬🇧
Sheffield, United Kingdom
University Hospitals of North Midlands
🇬🇧
Stoke, United Kingdom
Women's and Children's Hospital
🇦🇺
North Adelaide, South Australia, Australia
Lyell McEwin Hospital
🇦🇺
Adelaide, South Australia, Australia
St Vincent's Hospital Sydney
🇦🇺
Darlinghurst, New South Wales, Australia
Princess Alexandra Hospital
🇦🇺
Woolloongabba, Queensland, Australia
Wollongong Hospital
🇦🇺
Wollongong, New South Wales, Australia
Robina Hospital
🇦🇺
Robina, Queensland, Australia
Flinders Medical Centre
🇦🇺
Bedford Park, South Australia, Australia
Rahima Moosa Mother and Child Hospital
🇿🇦
Johannesburg, South Africa
St George Hospital
🇦🇺
Kogarah, New South Wales, Australia
Orange Health Service
🇦🇺
Orange, New South Wales, Australia
Prince of Wales Hospital
🇦🇺
Randwick, New South Wales, Australia
Royal Darwin Hospital
🇦🇺
Tiwi, Northern Territory, Australia
University Medical Center Utrecht
🇳🇱
Utrecht, Netherlands

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