Clinical trial NCT02660346: IL-10 Stratifying Tool for Towards Antibiotic Selection for MRSaB
Official title: A Multi-center Prospective Randomized Open Label Study of Utilizing Interleukin 10 (IL-10) Levels as a Guide for Antibiotic Selection for Methicillin Resistant Staphylococcus Aureus Bacteremia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Bacteremia
Keywords: IL-10
MRSA
Bacteremia
Lead sponsor: Sharp HealthCare
Sponsor class: OTHER
First posted: 2016-01-21
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Patients with MRSaB have high therapeutic failure rates and mortality rates. Recent studies have shown that an elevated IL-10 level is an independent risk factor of mortality. It may also serve as biomarker for very early risk stratification. The aim of this study is to compare the outcomes for patients with elevated IL-10 levels (≥8 pg/ml) when treated with standard antibiotic therapy (daptomycin or vancomycin) versus early aggressive therapy (daptomycin with ceftaroline) for the treatment of MRSaB.

Detailed description: Patients with MRSaB have primary therapeutic failure rates of 40-50% and high mortality rate of 10-50% when treated with the recommended standard antimicrobial therapy. (Sharp) local data for MRSaB for 2014 shows an all-cause mortality rate of 29%. Recent studies have been published that utilize the predictive biomarker, IL-10, aiding the understanding for the wide variability in mortality. Further studies are needed to elucidate the clinical relevance of utilizing IL-10 levels to optimize MRSaB management and whether or not patient outcomes are enhanced.

Under current standard treatment strategies, vancomycin 15 mg/kg IVPB every 12 hrs following a 30 mg/kg IVPB loading dose is the first line of antibiotic therapy initiated with known or suspected MRSaB. Only when patients have showed an unsatisfactory clinical response such as prolonged bacteremia and/or continued clinical signs of uncontrolled infection are more potent/aggressive and more expensive antibiotic choices considered in most cases. Even the time for consideration of such a switch is a matter of controversy, with current MRSA treatment guidelines recommending a switch after 7-days of failure.

Several recent studies have shown that an elevated IL-10 level is an independent risk factor of mortality. In animal models, it has been shown that the bacterial cell wall of Staphylococcus aureus stimulates the production of IL-10. A small study by Rose et al. showed that this observation is consistent in humans. In another study, the authors concluded that elevated IL-10 at the time of presentation is a predictive value of mortality in patients with MRSaB4. In addition, the authors concluded that IL-10 may serve as a biomarker for very early risk stratification, with selection of standard therapy for low-risk patients and more potent, expensive, and cumbersome antibiotic therapies reserved for the high-risk patients. Furthermore, it is postulated that treating high risk patients with aggressive/intensified therapy earlier may improve economic and microbiological outcomes, such as a decreased length of treatment, decreased time in the Intensive Care Unit, decreased length of stay in the hospital, and decreased duration of bacteremia.

The aim in this study is to compare the outcomes for patients with elevated IL-10 levels (≥ 8 pg/mL) when treated with standard antibiotic therapy versus early aggressive therapy for the treatment of MRSaB. Aggressive therapy is defined in study to be daptomycin (6-8mg/kg/day) with ceftaroline (600 mg q8hr).

Eligibility criteria: Inclusion Criteria:

* Adult (≥ 18 years of age) men or women.
* Diagnosis of MRSaB
* Has not been treated with antibiotics for MRSaB within 7 days of admission
* Has been on standard antibiotics for \< 72hrs prior to randomization
* In the opinion of the investigator, the subject must require and be a suitable candidate for IV antibiotic therapy.

Exclusion Criteria:

* Medical history of hypersensitivity or allergic reaction to vancomycin, or vancomycin derivatives, daptomycin or ceftaroline
* Severe allergy to cephalosporins, i.e. Type 1 reaction, especially IgE mediated anaphylaxis
* Comfort care patients
* Death within 72hrs of the start of antibiotic therapy
* Polymicrobial bacteremia: Staphylococcus aureus and another gram positive, gram negative or anaerobic pathogen
* Burns covering ≥ 10% of body.
* Pt currently enrolled in an investigational study

Primary outcomes:
measure: Time to bacteremia clearance
timeFrame: 1-4 weeks
Secondary outcomes:
measure: Comparison of IL-10 levels between standard and aggressive therapy treatments
timeFrame: About 2 months from blood draw to the batch results
Other outcomes:
Locations:
city: La Mesa
country: United States
facility: Sharp Grossmont Hospital
state: California
city: San Diego
country: United States
facility: Sharp Memorial Hospital
state: California
Study officials:
affiliation: Sharp HealthCare
name: DeAnn Cary, PhD
role: STUDY_DIRECTOR
References:
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