IL-10 Stratifying Tool for Towards Antibiotic Selection for MRSaB

January 30, 2018 updated by: Matthew Geriak, Sharp HealthCare

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Actual)

40

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 Locations

  • United States
    • California
      • La Mesa, California, United States, 91942
        • Sharp Grossmont Hospital
      • San Diego, California, United States, 92123
        • Sharp Memorial Hospital

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

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: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Group A - Daptomycin or Vancomycin
Standard of Therapy of physician's choice, usually daptomycin 6-8 mg/kg IVPB daily or vancomycin IVPB adjusted dose per site protocol with a goal vancomycin trough level: 15-20 mcg/mL.
Drug: Daptomycin
Control Arm Treatment if used as monotherapy. Study Arm Treatment if used in combination with ceftaroline.
Other Names:
  • Cubicin
Drug: Vancomycin
Control Arm Treatment
Other Names:
  • Vancocin HCL
Experimental: Group B - Daptomycin with Ceftaroline
Daptomycin (6-8 mg/kg/day IVPB daily) with Ceftaroline (600 mg IVPB q8hr) to start within 72hrs of hospital admission. Daptomycin will be renally adjusted per package insert. Ceftaroline will be renally adjusted per institutional renal dosing recommendations for Q8h.
Drug: Daptomycin
Control Arm Treatment if used as monotherapy. Study Arm Treatment if used in combination with ceftaroline.
Other Names:
  • Cubicin
Drug: Ceftaroline
Study Arm Treatment
Other Names:
  • Teflaro

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to bacteremia clearance
Time Frame: 1-4 weeks
To determine whether or not early aggressive antibiotic therapy are correlated to shorter time to bacteremia clearance compared to standard therapy
1-4 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Comparison of IL-10 levels between standard and aggressive therapy treatments
Time Frame: About 2 months from blood draw to the batch results
To determine whether or not patients who have high IL-10 levels treated with aggressive antibiotic therapy have better outcomes compared with standard therapy.
About 2 months from blood draw to the batch results

Collaborators and Investigators

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

Sponsor

Sharp HealthCare

Investigators

  • Study Director: DeAnn Cary, PhD, Sharp HealthCare

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

Helpful Links

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

November 1, 2015

Primary Completion (Actual)

September 15, 2017

Study Completion (Actual)

January 30, 2018

Study Registration Dates

First Submitted

October 21, 2015

First Submitted That Met QC Criteria

January 20, 2016

First Posted (Estimate)

January 21, 2016

Study Record Updates

Last Update Posted (Actual)

February 1, 2018

Last Update Submitted That Met QC Criteria

January 30, 2018

Last Verified

January 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IL-10 MRSaB

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

We do not plan on sharing any IPD with other researchers until the study is complete.

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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