Background
Staphylococcus aureus toxins
Antibiotics which act as protein synthesis inhibitors
Clindamycin compared to β-lactam antibiotics for anti-toxin therapy
Objective
Hypothesis
Methods
Study setting
Inclusion criteria
Age group | Heart rate (beats/min) | Respiratory rate (breaths/min) | Leucocyte count × 103/mm3 | Systolic BP (mmHg) | |
---|---|---|---|---|---|
Tachycardia | Bradycardia | ||||
1 month–1 year | > 180 | < 90 | > 60 | > 17.5 or < 5 | < 100 |
2–5 years | > 140 | NA | > 40 | > 15.5 or < 6 | < 94 |
6–12 years | > 130 | NA | > 20 | > 13.5 or < 4.5 | < 105 |
13–15 years | > 90 | NA | > 20 | > 11 or < 4.5 | < 117 |
Exclusion criteria
Interventions
Control group
Combination therapy group
Criteria for discontinuing or modifying allocated interventions
Strategies to improve adherence to the protocol, and any procedures for monitoring adherence
Relevant concomitant care and interventions that are permitted or prohibited during the trial
Outcomes
Primary outcome
Secondary outcome measures
Participant timeline (Table 2)
Eligibility screening
Timepoint | Day 1 | Day 2 | Day 3 | Day 4 | Day 5 | Day 6 | Day 7 | Da y 10 | Day 14 | Day 15–89 | Day 90 |
---|---|---|---|---|---|---|---|---|---|---|---|
Enrolment | |||||||||||
Eligibility screen | X | ||||||||||
Informed consent | X | ||||||||||
Demographic details | X | ||||||||||
Clinical details | X | ||||||||||
Randomisation | X | ||||||||||
Interventions | |||||||||||
Standard therapy (flucloxacillin/cefazolin or vancomycin/daptomycin) | X | X | X | X | X | X | X | X | Xa | Xa | |
Clindamycin (if in combination group) | X | X | X | X | X | X | X | ||||
Assessments | |||||||||||
Blood cultures | X | Xb | Xb | ||||||||
FBC, EUC, LFTs, CRP | X | X | X | X | X | ||||||
Check SIRS score | X | X | X | X | X | X | X | X | X | ||
Check vital observations | X | X | X | X | X | ||||||
Clinical progress assessment | X | X | X | X | X | Weekly if inpatient | X | ||||
Vital status | X | X | X | X | X | X | |||||
Additional data | X |
Informed consent
Paediatric-specific consent issues
Randomisation and blinding
Days 2–90
Endpoint assessment
Discontinuation/withdrawal of participants from trial treatment
Sample size considerations
Data management
Data collection
Data entry and storage
Statistical methods
Pre-specified subgroup analyses
Data safety and monitoring board
Safety aspects of the trial
Adverse events and adverse reaction (solicited and unsolicited)
-
Grade 1: mild symptoms. Causes nil or minimal interference with usual social and functional activities. No intervention indicated.
-
Grade 2: moderate symptoms. Interferes with but does not limit usual social and functional activities. Intervention is indicated.
-
Grade 3: severe symptoms. Inability to perform usual social and functional activities. Intervention or hospitalisation is needed.
-
Grade 4: potentially life-threatening symptoms. Inability to perform basic self-care functions. Intervention is indicated to prevent permanent impairment, persistent disability, or death.
-
Grade 5: death related to adverse event.
Serious adverse events
-
◦ results in death;
-
◦ is life-threatening;
-
◦ results in hospitalisation (initial or prolongation);
-
◦ results in disability or permanent damage; or
-
◦ is a medically important event or reaction.