Staphylococcus Aureus Network Adaptive Platform Trial (SNAP)

March 21, 2024 updated by: University of Melbourne
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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

6000

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Australia
    • Australia Capital Territory
      • Garran, Australia Capital Territory, Australia, 2605
        • Not yet recruiting
        • Canberra Hospital
        • Principal Investigator:
          • Heather Wilson
    • New South Wales
      • Blacktown, New South Wales, Australia, 2148
        • Recruiting
        • Blacktown Hospital
        • Principal Investigator:
          • Ravindra Dotel
      • Camperdown, New South Wales, Australia, 2050
        • Recruiting
        • Royal Prince Alfred Hospital
        • Principal Investigator:
          • Sebastian VanHal
      • Concord, New South Wales, Australia, 2139
        • Recruiting
        • Concord Repatriation and General Hospital
        • Principal Investigator:
          • Genevieve McKew
        • Sub-Investigator:
          • Timothy Gray
      • Darlinghurst, New South Wales, Australia, 2010
        • Not yet recruiting
        • St Vincent's Hospital Sydney
        • Principal Investigator:
          • Gail Matthews
      • Kingswood, New South Wales, Australia, 2747
        • Recruiting
        • Nepean Hospital
        • Principal Investigator:
          • Archana Sud
      • Kogarah, New South Wales, Australia, 2217
        • Not yet recruiting
        • St George Hospital
        • Principal Investigator:
          • Richard Sullivan
      • Liverpool, New South Wales, Australia, 2170
        • Recruiting
        • Liverpool Hospital
        • Principal Investigator:
          • Hong Foo
      • New Lambton Heights, New South Wales, Australia, 2305
        • Recruiting
        • John Hunter Hospital
        • Principal Investigator:
          • Joshua Davies
      • Newcastle, New South Wales, Australia, 2305
        • Recruiting
        • John Hunter Children's Hospital
        • Principal Investigator:
          • Coen Butters
      • Randwick, New South Wales, Australia, 2031
        • Recruiting
        • Sydney Children's Hospital
        • Principal Investigator:
          • Brendan McMullan
      • Randwick, New South Wales, Australia, 2031
        • Not yet recruiting
        • Prince of Wales Hospital
        • Principal Investigator:
          • Jeffrey Post
      • Westmead, New South Wales, Australia, 2145
        • Recruiting
        • Westmead Hospital
        • Principal Investigator:
          • Matthew O'Sullivan
      • Westmead, New South Wales, Australia, 2145
        • Recruiting
        • The Children's Hospital at Westmead
        • Principal Investigator:
          • Philip Britton
      • Wollongong, New South Wales, Australia, 2500
        • Recruiting
        • Wollongong Hospital
        • Principal Investigator:
          • Niladri Ghosh
    • Northern Territory
      • Tiwi, Northern Territory, Australia, 0811
        • Not yet recruiting
        • Royal Darwin Hospital
        • Principal Investigator:
          • Jane Davies
        • Sub-Investigator:
          • Josh Francis
        • Sub-Investigator:
          • Kate Proudmore
    • Queensland
      • Birtinya, Queensland, Australia, 4575
        • Recruiting
        • Sunshine Coast University Hospital
        • Principal Investigator:
          • David Sowden
        • Sub-Investigator:
          • Shradha Subedi
      • Cairns, Queensland, Australia, 4870
        • Recruiting
        • Cairns Hospital
        • Principal Investigator:
          • Simon Smith
      • Herston, Queensland, Australia, 4029
        • Recruiting
        • Royal Brisbane and Women's Hospital
        • Principal Investigator:
          • David Paterson
      • Meadowbrook, Queensland, Australia, 4131
        • Not yet recruiting
        • Logan Hospital
        • Principal Investigator:
          • Vichitra Sukumaran
      • South Brisbane, Queensland, Australia, 4101
        • Recruiting
        • Queensland Children's Hospital
        • Principal Investigator:
          • Clare Nourse
      • Southport, Queensland, Australia, 4215
        • Recruiting
        • Gold Coast University Hospital
        • Principal Investigator:
          • Katherine Garnham
      • Woolloongabba, Queensland, Australia, 4102
        • Not yet recruiting
        • Princess Alexandra Hospital
        • Principal Investigator:
          • Andrew Henderson
    • South Australia
      • Adelaide, South Australia, Australia, 5112
        • Recruiting
        • Lyell McEwin Hospital
        • Principal Investigator:
          • Mark Boyd
      • Bedford Park, South Australia, Australia, 5042
        • Not yet recruiting
        • Flinders Medical Centre
        • Principal Investigator:
          • Nicholas Anagnostou
      • North Adelaide, South Australia, Australia, 5006
        • Not yet recruiting
        • Women's and Children's Hospital
        • Principal Investigator:
          • Nan Vasilunas
    • Tasmania
      • Hobart, Tasmania, Australia, 7000
        • Not yet recruiting
        • Royal Hobart Hospital
        • Principal Investigator:
          • Peter Leung
      • Launceston, Tasmania, Australia, 7250
        • Recruiting
        • Launceston Hospital
        • Principal Investigator:
          • Ali Trad
    • Victoria
      • Ballarat, Victoria, Australia, 3350
        • Recruiting
        • Grampians Health
        • Principal Investigator:
          • Robert Commons
      • Bendigo, Victoria, Australia, 3550
        • Recruiting
        • Bendigo Health
        • Principal Investigator:
          • Andrew Mahony
      • Box Hill, Victoria, Australia, 3128
        • Recruiting
        • Box Hill Hospital
        • Principal Investigator:
          • LynLi Lim
        • Sub-Investigator:
          • Stephen Guy
      • Clayton, Victoria, Australia, 3168
        • Not yet recruiting
        • Monash Medical Centre
        • Principal Investigator:
          • Ben Rogers
        • Sub-Investigator:
          • Richard Doherty
      • Footscray, Victoria, Australia, 3011
        • Recruiting
        • Western Health- Footscray Hospital & Sunshine Hospital
        • Contact:
      • Frankston, Victoria, Australia, 3199
        • Not yet recruiting
        • Frankston Hospital
        • Principal Investigator:
          • Kasha Singh
      • Geelong, Victoria, Australia, 3220
        • Recruiting
        • Geelong Hospital
        • Principal Investigator:
          • Eugene Athan
      • Heidelberg, Victoria, Australia, 3084
        • Recruiting
        • Austin Hospital
        • Principal Investigator:
          • Natasha Holmes
      • Melbourne, Victoria, Australia, 3004
        • Recruiting
        • Alfred Hospital
        • Contact:
          • James McMahon
        • Principal Investigator:
          • James McMahon
      • Parkville, Victoria, Australia, 3050
        • Recruiting
        • Royal Melbourne Hospital
        • Principal Investigator:
          • Justin Denholm
      • Parkville, Victoria, Australia, 3052
        • Recruiting
        • Royal Children's Hospital Melbourne
        • Contact:
      • Shepparton, Victoria, Australia, 3630
        • Recruiting
        • Goulburn Valley Health
        • Contact:
      • Traralgon, Victoria, Australia, 3844
        • Not yet recruiting
        • La Trobe Regional Hospital
        • Principal Investigator:
          • Zaal Meher-Homji
    • Western Australia
      • Murdoch, Western Australia, Australia, 6150
        • Recruiting
        • Fiona Stanley Hospital
        • Principal Investigator:
          • Owen Robinson
      • Nedlands, Western Australia, Australia, 6009
        • Recruiting
        • Perth Children's Hospital
        • Principal Investigator:
          • Asha Bowen
        • Sub-Investigator:
          • Anita Campbell
      • Perth, Western Australia, Australia, 6000
        • Recruiting
        • Royal Perth Hospital
        • Principal Investigator:
          • Owen Robinson
  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T3M 1M4
        • Recruiting
        • South Health Campus
        • Principal Investigator:
          • Ranjani Somayaji
      • Calgary, Alberta, Canada, T1Y 6J4
        • Recruiting
        • Peter Lougheed Centre
        • Principal Investigator:
          • Ranjani Somayaji
      • Calgary, Alberta, Canada, T2N4Z6
        • Recruiting
        • University of Calgary - Foothills Medical Center
        • Principal Investigator:
          • Ranjani Somayaji
      • Calgary, Alberta, Canada, T2V 1P9
        • Recruiting
        • Rockyview Hospital
        • Principal Investigator:
          • Ranjani Somayaji
      • Edmonton, Alberta, Canada, T6G2B7
        • Recruiting
        • University of Alberta Hospital
        • Principal Investigator:
          • Stephanie Smith
    • British Columbia
      • Richmond, British Columbia, Canada, V6X1A2
        • Not yet recruiting
        • Richmond General Hospital
        • Principal Investigator:
          • Clement Kwok
      • Vancouver, British Columbia, Canada, V5Z1M9
        • Recruiting
        • Vancouver General Hospital
        • Principal Investigator:
          • Jennifer Grant
    • Manitoba
      • Winnipeg, Manitoba, Canada, R3A1R9
        • Not yet recruiting
        • Health Sciences Centre Winnipeg
        • Principal Investigator:
          • Terry Wuerz
    • Newfoundland and Labrador
      • Saint John's, Newfoundland and Labrador, Canada, A1B3V6
        • Recruiting
        • Eastern Health - Health Sciences Centre (Memorial University)
        • Principal Investigator:
          • Peter Daley
    • Ontario
      • East York, Ontario, Canada, M5G2C4
        • Not yet recruiting
        • University Health Network
        • Principal Investigator:
          • Bryan Coburn
      • East York, Ontario, Canada, M4C3E7
        • Recruiting
        • Toronto East Health Network
        • Principal Investigator:
          • Christopher Kandel
      • Hamilton, Ontario, Canada, L8P1A2
        • Recruiting
        • Hamilton Health Sciences Center
        • Principal Investigator:
          • Dominik Mertz
      • Kingston, Ontario, Canada, K7L2V7
        • Recruiting
        • Kingston Health Sciences Centre
        • Principal Investigator:
          • Anthony Bai
      • Ottawa, Ontario, Canada, K1H8L6
        • Recruiting
        • Ottawa Hospital
        • Principal Investigator:
          • Derek MacFadden
      • Sault-Sainte-Marie, Ontario, Canada, P6B 0A8
        • Recruiting
        • Sault Area Hospital
        • Principal Investigator:
          • Lucas Castellani
      • St. Catharines, Ontario, Canada, L2S 0A9
        • Recruiting
        • Niagara Health - St. Catharines Site
        • Principal Investigator:
          • David McCullagh
      • Toronto, Ontario, Canada, M4N3M5
        • Recruiting
        • Sunnybrook Health Sciences Centre
        • Principal Investigator:
          • Nick Daneman
      • Toronto, Ontario, Canada, M1L 1W1
        • Not yet recruiting
        • Unity Health
        • Principal Investigator:
          • Matthew Muller
        • Principal Investigator:
          • Kevin Schwarz
      • Toronto, Ontario, Canada, M5G1X5
        • Recruiting
        • Sinai Heath System
        • Principal Investigator:
          • Jennie Johnstone
    • Quebec
      • Montréal, Quebec, Canada, H3T1E2
        • Not yet recruiting
        • Jewish General Hospital
        • Principal Investigator:
          • Leighanne Parkes
      • Montréal, Quebec, Canada, H4A3J1
        • Recruiting
        • McGill University Health Centre
        • Principal Investigator:
          • Matthew Cheng
      • Saint-Jérôme, Quebec, Canada, J7Z5T3
        • Recruiting
        • Hopital regional de saint jerome
        • Principal Investigator:
          • Sébastien Poulin
      • Sherbrooke, Quebec, Canada, J1H 5H3
        • Not yet recruiting
        • University of Sherbrooke Health Centre- USHC/CHUS
        • Principal Investigator:
          • Alex Carignan
  • Israel
      • Haifa, Israel, 310960
        • Recruiting
        • Rambam Health Care Campus
        • Principal Investigator:
          • Mical Paul
      • Petah tikva, Israel, 49100
        • Not yet recruiting
        • Beilinson Hospital
        • Principal Investigator:
          • Dafna Yahav
      • Petah tikva, Israel, 49100
        • Recruiting
        • Sheba Medical Centre
        • Principal Investigator:
          • Dafna Yahav
  • Netherlands
      • Nijmegen, Netherlands
        • Recruiting
        • Radboud University Medical Center
        • Principal Investigator:
          • Nynke Jager
      • Utrecht, Netherlands
        • Recruiting
        • University Medical Center Utrecht
        • Principal Investigator:
          • Marjolein Hensgens
  • New Zealand
      • Auckland, New Zealand, 1023
        • Recruiting
        • Starship Hospital
        • Principal Investigator:
          • Rachel Webb
      • Auckland, New Zealand, 2025
        • Recruiting
        • KidzFirst
        • Principal Investigator:
          • Rachel Webb
      • Hamilton, New Zealand, 3240
        • Recruiting
        • Waikato Hospital
        • Principal Investigator:
          • Paul Huggan
      • Tauranga, New Zealand, 3112
        • Recruiting
        • Tauranga Hospital
        • Principal Investigator:
          • Kate Grimwade
      • Whangarei, New Zealand, 0148
        • Not yet recruiting
        • Whangarei Hospital
        • Principal Investigator:
          • David Hammer
    • Auckland
      • Grafton, Auckland, New Zealand, 1023
        • Recruiting
        • Auckland City Hospital
        • Principal Investigator:
          • Mark Hobbs
      • Otahuhu, Auckland, New Zealand, 1640
        • Recruiting
        • Middlemore Hospital
        • Principal Investigator:
          • Genevieve Walls
        • Sub-Investigator:
          • Rachel Webb
        • Sub-Investigator:
          • Susan Morpeth
      • Takapuna, Auckland, New Zealand, 0620
        • Not yet recruiting
        • North Shore Hospital
        • Principal Investigator:
          • Nick Gow
    • Canterbury
      • Christchurch, Canterbury, New Zealand, 8011
        • Not yet recruiting
        • Christchurch Hospital
        • Principal Investigator:
          • Sarah Metcalf
    • Lower Hutt
      • Boulcott, Lower Hutt, New Zealand, 5010
        • Not yet recruiting
        • Hutt Valley Hospital
        • Principal Investigator:
          • Matthew Kelly
    • Nelson
      • Nelson South, Nelson, New Zealand, 7010
        • Not yet recruiting
        • Nelson Hospital
        • Principal Investigator:
          • Richard Everts
    • Otago
      • Dunedin, Otago, New Zealand, 9016
        • Not yet recruiting
        • Dunedin Hospital
        • Principal Investigator:
          • Brendan Arnold
    • Wellington
      • Newtown, Wellington, New Zealand, 6021
        • Recruiting
        • Wellington Hospital
        • Principal Investigator:
          • Max Bloomfield
  • Singapore
      • Singapore, Singapore, 308433
        • Recruiting
        • Tan Tock Seng Hospital
        • Principal Investigator:
          • David Lye
      • Singapore, Singapore, 119228
        • Not yet recruiting
        • National University Hospital
      • Singapore, Singapore, 168753
        • Not yet recruiting
        • Singapore General Hospital
        • Principal Investigator:
          • Shirin Kalimuddin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

PLATFORM Inclusion Criteria:

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

1. Staphylococcus aureus complex grown from ≥1 blood culture 2. 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:

  1. Time of anticipated platform entry is greater than 72 hours post collection of the index blood culture

    a) Where the time of culture collection is not recorded, the time of laboratory registration of the sample will be used as an alternative

  2. Polymicrobial bacteraemia, defined as more than one organism (at species level) in the index blood cultures, excluding those organisms judged to be contaminants by either the microbiology laboratory or treating clinician
  3. Patient currently being treated with a systemic antibacterial agent that cannot be ceased (unless antibiotic is listed in Table 1, which specifies allowed antibiotics with limited absorption from the gastrointestinal tract or negligible antimicrobial activity against S. aureus)
  4. Known previous participation in SNAP
  5. 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
  6. Treating team deems enrolment in the study is not in the best interest of the patient
  7. Treating team believes that death is imminent and inevitable
  8. Patient is for end-of-life care and antibiotic treatment is considered not appropriate
  9. Patient <18 years of age and paediatric recruitment not approved at recruiting site

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:

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

Exclusion criteria:

  1. 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) or severe diarrhoea from any cause
  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:

  1. For PSSA silo: Index blood culture is penicillin-susceptible
  2. For MSSA silo: Index blood culture isolate is methicillin-susceptible but penicillin resistant

Exclusion Criteria (PSSA & MSSA):

1. >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) 2. History of type I hypersensitivity reaction (i.e. anaphylaxis or angioedema) to any penicillin or cephalosporin 3. History of severe delayed reaction (e.g. allergic interstitial nephritis, cutaneous vasculitis, Stevens-Johnson, DRESS, etc.) to any penicillin or cephalosporin 4. 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.

    5. Treating team deems enrolment in this domain is not in the best interest of the patient 6. 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.

MRSA TREATMENT DOMAIN (backbone)

Inclusion Criteria:

1. MRSA confirmed microbiologically

Exclusion Criteria:

  1. Time to allocation reveal is >72 hours from time of index blood culture collection

  2. Severe allergy to any beta-lactam (including cefazolin)

    1. Immediate severe allergy: Anaphylaxis/angioedema
    2. 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.

  3. Non-severe rash to cefazolin

    a) 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.

  4. Severe allergy or non-severe rash to both vancomycin AND daptomycin

    a) 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.

  5. Treating team deems enrolment in the domain is not in the best interest of the patient

EARLY ORAL SWITCH DOMAIN

Inclusion Criteria:

Day 7 (+/- 2 days):

  1. 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
  2. Afebrile (<37.8°C) for the past 72 hours (at time of judging eligibility)
  3. 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)
  4. 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):

  1. 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)
  2. Afebrile (<37.8°C) for the past 72 hours (at time of judging eligibility)
  3. 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:

  1. Adherence to oral agents unlikely (as judged by site PI in consultation with the treating team)
  2. Unreliable gastrointestinal absorption (e.g. vomiting, diarrhoea, nil by mouth, anatomical reasons)
  3. There are no appropriate oral antibiotics due to contraindications, drug availability, or antibiotic resistance
  4. Ongoing IV therapy unsuitable e.g. no IV access
  5. Clinician deems not appropriate for early oral switch

  6. Patient no longer willing to participate in domain

    a) 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

  7. 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):

  1. Presence of prosthetic cardiac valve, pacemaker or other intracardiac implant
  2. Known presence of intravascular clot (excluding superficial peripheral IV line-related thrombophlebitis), graft or other intravascular prosthetic material
  3. Intravascular/intracardiac infections (e.g. endocarditis, mycotic aneurysm)
  4. Presence of other intracardiac abnormalities felt to put patient at increased risk of endocarditis (e.g., bicuspid aortic valve)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Methicillin-resistant staphylococcus aureus (MRSA) - Standard Therapy Arm (backbone therapy)

Vancomycin or Daptomycin - Standard Therapy Arm

Either intravenous vancomycin dosed as per Australian Therapeutic Guidelines: This includes a loading dose of 25 mg/kg (up to 3000mg) if considered appropriate by the treating clinician, initial maintenance dosing at 15-20 mg/kg q12h, with subsequent adjustment to maintain area under the concentration-time curve (AUC) of 400 to 600 mg.hr/L OR trough levels at 10-20 mg/L, and the initial level taken 48-72 hours after the initiation of the first dose. Daptomycin 8-10mg/kg per day intravenously. The choice of vancomycin or daptomycin will be at the clinician's discretion. Dosing will be based on renal function.
Experimental: Methicillin-resistant staphylococcus aureus (MRSA) - Standard + B-Lactam Arm (backbone therapy)

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.
Drug: Cefazolin
Cefazolin
Drug: Vancomycin
Vancomycin or Daptomycin
Other Names:
  • Daptomycin
No Intervention: Methicillin-susceptible staphylococcus aureus (MSSA) - Standard Therapy Arm (backbone therapy)

Flucloxacillin or cloxacillin - Standard Therapy Arm

Either intravenous flucloxacillin/cloxacillin 2g 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 renal impairment or critical illness the intravenous flucloxacillin administration dose will be adjusted.
Experimental: Methicillin-susceptible staphylococcus aureus (MSSA) - Interventional Arm (backbone therapy)

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.
Drug: Cefazolin
Cefazolin
No Intervention: Penicillin-susceptible staphylococcus aureus (PSSA) - Standard Therapy Arm (backbone therapy)

Flucloxacillin or cloxacillin - Standard Therapy Arm

Either intravenous flucloxacillin/cloxacillin 2g 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 renal impairment or critical illness the intravenous flucloxacillin administration dose will be adjusted.
Experimental: Penicillin-susceptible staphylococcus aureus (PSSA) - Interventional Arm (backbone therapy)

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.
Drug: Penicillin
benzylpenicillin
Other Names:
  • Benzylpenicillin
  • Penicillin G
No Intervention: No adjunctive treatment in combination with MRSA or MSSA or PSSA backbone therapy arm

No adjunctive therapy + backbone therapy arm for MRSA or MSSA or PSSA

Participants with either MRSA or MSSA or PSSA will have no adjunctive therapy in combination with their backbone therapy arm.
Experimental: Adjunctive treatment in combination with MRSA or MSSA or PSSA backbone therapy arm
Adjunctive therapy + backbone therapy arm for MRSA or MSSA or PSSA Intravenous clindamycin (or lincomycin) 600mg every 8 hours for 5 days. No dosage adjustment is needed to renal impairment.
Drug: Clindamycin
Clindamycin
Other Names:
  • Lincomycin
No Intervention: Continue intravenous antibiotic therapies (backbone +/- adjunctive therapy) - standard of care arm

Backbone therapy arm for MRSA or MSSA or PSSA +/- adjunctive therapy will continue on intravenous antibiotic treatment for the length of time as per usual standard of care.

Participants eligibility is assessed at Day 7 (+/- 2 days) if eligible will be randomised if not eligible then eligibility will be assess again at Day 14(+/- 2 days). If eligibility is not met at day 14 then participant is excluded from this domain.
Experimental: Switch to oral antibiotics at trial day 7 (+/- 2 days) or Day 14 (+/- 2 days) if eligible.

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.
Other: Effectiveness of early switch to oral antibiotics
This involves testing a strategy rather than individual antibiotic agents

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
All-cause mortality at 90 days after platform entry
Time Frame: 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.
From randomisation (day 1) until day 90

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
All-cause mortality at 14, 28 and 42 days after platform entry
Time Frame: 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.
From randomisation (day 1) until day 14, 28, and 42
Duration of survival censored at 90 days after platform entry
Time Frame: 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.
From randomisation (day 1) until day 90
Length of stay of acute index inpatient hospitalisation for those surviving until hospital discharge (excluding HITH/COPAT/OPAT/rehab) truncated at 90 days after platform entry.
Time Frame: From randomisation (day 1) until day 90
Acute index hospitalisation is defined as a continuous admission to an inpatient healthcare facility where the patient was recruited.
From randomisation (day 1) until day 90
Length of stay of total index hospitalisation for those surviving until hospital discharge (including HITH/COPAT/OPAT/rehab) truncated at 90 days after platform entry.
Time Frame: From randomisation (day 1) until day 90
Total index hospitalisation is defined as a continuous admission to any healthcare facility, including rehabilitation hospitals, and hospital-in-the-home or outpatient parenteral antimicrobial therapy services.
From randomisation (day 1) until day 90
Time to being discharged alive from the total index hospitalisation (including HITH/COPAT/OPAT/rehab) truncated at 90 days after platform entry
Time Frame: From randomisation (day 1) until day 90
and all deaths within 90 days will be considered '90 days'
From randomisation (day 1) until day 90
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).
Time Frame: 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.
From randomisation (day 1) until day 90
Diagnosis of new foci between 14 and 90 days after platform entry.
Time Frame: 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.
From randomisation (day 1) until day 90
C. difficile diarrhoea as determined by a clinical laboratory in the 90 days following platform entry for participants ≥2 years of age.
Time Frame: 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.
From randomisation (day 1) until day 90
Number of participants with Serious adverse reactions (SARs) in the 90 days following platform entry
Time Frame: From randomisation (day 1) until day 90
SARs defined only as events that are attributable to one or more study interventions
From randomisation (day 1) until day 90
Health economic costs as detailed in the cost utility analysis appendix.
Time Frame: From randomisation (day 1) until day 90
Including hospital length of stay, readmissions, and patient employment status.
From randomisation (day 1) until day 90
Proportion of participants who have returned to their usual level of function at day 90.
Time Frame: 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.
From randomisation (day 1) until day 90
Desirability of outcome ranking 1 (modified Antibiotic Resistance Leadership Group version)
Time Frame: From randomisation (day 1) until day 90
unable to insert modified ARLG table
From randomisation (day 1) until day 90
Desirability of outcome ranking 2 (SNAP version)
Time Frame: From randomisation (day 1) until day 90
unable to insert SNAP DOOR table
From randomisation (day 1) until day 90

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Melbourne

Collaborators

Radboud University Medical Center
Sunnybrook Health Sciences Centre
UMC Utrecht
Tan Tock Seng Hospital
McGill University Health Centre/Research Institute of the McGill University Health Centre
Menzies School of Health Research
Berry Consultants
The University of Queensland
Telethon Kids Institute
Queensland University of Technology
The Peter Doherty Institute for Infection and Immunity
Aotearoa Clinical Trials

Investigators

  • Study Chair: A/Prof Steven Tong, University of Melbourne
  • Study Chair: Prof Joshua Davies, Menzies School of Research

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 16, 2022

Primary Completion (Estimated)

December 1, 2025

Study Completion (Estimated)

December 1, 2025

Study Registration Dates

First Submitted

April 25, 2021

First Submitted That Met QC Criteria

November 23, 2021

First Posted (Actual)

November 30, 2021

Study Record Updates

Last Update Posted (Actual)

March 25, 2024

Last Update Submitted That Met QC Criteria

March 21, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CT19029

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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