Combination Antibiotic Therapy for Methicillin Resistant Staphylococcus Aureus Infection

Phase 3TerminatedNCT02365493

Menzies School of Health Research358 enrolled

Overview

The aim of this clinical trial is to determine whether a novel combination antibiotic treatment (vancomycin/daptomycin + beta-lactam) is superior to the standard antibiotic treatment (vancomycin/daptomycin) for hospitalised adults with Methicillin Resistant Staphylococcus aureus bacteraemia. The hypothesis is that the addition of beta-lactam antibiotics (these are antibiotics from the penicillin family) to the standard therapy will lead to more efficient bacterial killing and hence lead to faster clearance of bacteria from the blood stream and other areas of infection, thereby reducing the risk of the spread of infection and death. The study design is an investigator-initiated, multi-centre, open-label, randomised controlled trial. This will include 440 participants diagnosed with Methicillin Resistant Staphylococcus aureus bacteraemia recruited over a period of 4 years (July 2015 - June 2019) from within Infectious Diseases inpatient units across 21 hospital sites including 18 from within Australia and 3 located in Singapore. Participation will be voluntary and subject to informed consent. The participants will be randomised 1:1 to either the standard therapy group or combination therapy group. The combination therapy will include a treatment of intravenous beta-lactam for the first 7 days of treatment, in addition to the standard treatment (either vancomycin or daptomycin). The primary outcome measure will be complication-free survival 90 days post randomisation.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

358

Conditions

Methicillin-Resistant Staphylococcus Aureus

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Age \>= 18 years. 2. ≥1 set of blood cultures positive for MRSA 3. Able to be randomized within 72 hours of blood cultures being collected. 4. Likely to remain as inpatient for 7 days following randomization Exclusion Criteria: 1. Previous type 1 hypersensitivity reaction to ß-lactams 2. Polymicrobial bacteraemia (not counting contaminants) 3. Previous participation in the trial 4. Known pregnancy 5. Current β-lactam antibiotic therapy which cannot be ceased or substituted 6. Participant's primary clinician unwilling to enrol patient 7. Moribund (expected to die in next 48 hours with or without treatment) 8. Treatment limitations which preclude the use of antibiotics Note that we are NOT planning to exclude participants with renal failure.

Locations (30)

Blacktown Hospital

Blacktown, New South Wales, Australia

Royal Prince Alfred Hospital

Camperdown, New South Wales, Australia

Concord Repatriation General Hospital

Concord, New South Wales, Australia

St Vincent's Hospital

Darlinghurst, New South Wales, Australia

Nepean Hospital

Kingswood, New South Wales, Australia

Outcomes

Primary Outcomes

Complication-free 90 day survival

Composite outcome at 90 days - any of: 1. All-cause mortality 2. Persistent bacteraemia at day 5 or beyond 3. Microbiological relapse - positive blood culture for MRSA at least 72 hours after a preceding negative culture 4. Microbiological treatment failure. Positive sterile site culture for MRSA at least 14 days after randomisation.