CASSETTE - Clindamycin Adjunctive therapy for Severe Staphylococcus aurEus Treatment Evaluation – An investigator-initiated, multi-centre, parallel group, open labelled pilot randomised controlled trial
CASSETTE – Clindamycin Adjunctive therapy for Severe Staphylococcus aureus Treatment Evaluation. A multi-centre, pilot RCT to determine if 7 days of clindamycin in combination with standard therapy will lead to a faster resolution of systemic inflammation than standard therapy alone in adults and children with severe S. aureus infection
Menzies School of Health Research
60 participants
Jul 10, 2018
Interventional
Conditions
Summary
The primary objective of this pilot study is to determine if 7 days of clindamycin in combination with standard therapy will lead to a faster resolution of systemic inflammation than standard therapy alone in adults and children with severe methicillin-susceptible S. aureus (MSSA) infection. We hypothesise that the addition of lincosamides (clindamycin) to standard therapy will lead to more rapid resolution of local and systemic inflammation due to blockade of exotoxin production by Staphylococcus aureus(SA). The results of this pilot study will be used to determine the feasibility and refine study design of a definitive randomised controlled trial assessing the effects of adjunctive lincosamide on patient-centred outcomes in children and adults with severe MSSA infection.
Eligibility
Inclusion Criteria9
- Age – both children and adults will be eligible. Infants must have a corrected age of greater than or equal to 28 days.
- S. aureus cultured from at least one clinically relevant specimen (Including an isolation in a polymicrobial culture when the other isolates are determined by the PI to be non-significant)
- Able to be randomised within 72 hours of index culture
- Likely to remain as inpatient for at least 7 days following randomisation (or is accessible for follow up by the site Principal Investigator. eg Hospital in the home (HITH)
- Index culture drawn no later than 48 hours after hospital admission
- Severe disease – at least one of
- 1 Septic shock (including Staphylococcal toxic shock syndrome)
- 2 Necrotising lung/pleural space infection
- 3 Complicated skin/soft tissue/osteoarticular infection which is multifocal and non-contiguous [e.g. pyomyositis, non-contiguous multifocal pyogenic skin infection (abscess/carbuncle)]
Exclusion Criteria10
- Previous severe allergic reaction to both flucloxacillin and cefazolin (for MSSA), or to both vancomycin and daptomycin (for MRSA), or to lincosamides
- Previous participation in the trial
- Known pregnancy
- Currently receiving a lincosamide or other potentially anti-toxin antibiotic which cannot be ceased or substituted
- Participant’s primary clinician unwilling to enrol patient
- Moribund (expected to die in next 24 hours with or without treatment)
- Treatment limitations which preclude the use of antibiotics
- Significant immunosuppression (Prednisolone >0.5mg per kg per day for greater than or equal to 14 days in the last 30 days, other immunosuppressive medication, known human immunodeficiency virus (HIV) with CD4 count<200 cells/microlitre, congenital immunodeficiency)
- Necrotising fasciitis
- Current clostridium difficile associated diarrhoea or severe diarrhoea from any cause
Interested in this trial?
Get notified about updates and connect with the research team.
Interventions
Arm1: Interventional Group (Combination therapy group) - will receive standard therapy as per control group in Arm 2. In addition, they will also receive open label clindamycin (10mg/kg/dose up to 600mg 4 times per day intravenously in both adult and children) for 7 days (day 1 being the day of randomisation – hence the actual duration of clindamycin use will range from 6 to 7 days, depending on the time of day that the patient is randomized). The intravenous route for clindamycin is recommended but not mandated for the entire duration of therapy (7days). If switch to oral therapy is thought to be necessary and appropriate by the site PI, transition to oral clindamycin 450mg 3 times per day for adults or 10mg/kg/dose orally 3 times per day (max 450mg) for children is recommended. Each dose of medication will be recorded in the case report form and analysised for adherence to at least 75%of the dosage over the 7 days. This will form part of the study analysis.
Locations(11)
View Full Details on ANZCTR
For the most up-to-date information, visit the official listing.
ACTRN12617001416381