Polymyxin B Monotherapy vs Combination Therapy in Critically Ill Patients With Multi-drug Resistant Pathogens (MUSEUM)

February 7, 2019 updated by: University of Puerto Rico

Polymyxin B Monotherapy Versus Polymyxin B-Carbapenem Combination Therapy in Critically Ill Patients With Multi-drug Resistant Gram-negative Infection: A Prospective, Parallel-Group, Double-Blind, Randomized Controlled Study

The purpose of this study is to assess the safety and efficacy of polymyxin B as monotherapy versus a combined polymyxin B-carbapenem therapy against multidrug-resistant (MDR) gram negative infections. The investigators intend to evaluate if this synergistic drug regimen correlates with improved outcomes against gram-negative infections in critically ill patients including: better clinical resolution, reduced length of stay at hospital, reduced length of stay at the intensive care unit, and less recurrence of infection.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

The "MUSEUM" trial is a single-center, prospective, parallel-group, double-blind, randomized, controlled study design. The trial will be conducted at the Intensive Care Unit of the Puerto Rico Trauma Hospital located in San Juan, Puerto Rico. Patients with clinical and microbiological evidence of an Multi-drug resistant infection related to Hospital-acquired pneumonia (HAP), Ventilator-associated pneumonia (VAP), Complicated Urinary tract infection (cUTI) or Bloodstream infection (BSI) will be considered candidates for the study. The pathogen should be resistant to all antibiotics except to polymyxin B. With a predicted survival rate of 67% (hazard ratio of 0.33), a significance of α = 0.05, power of 80%, and assuming a dropout rate of 15%, the estimated sample size is n = 40 patients (20 per group). In terms of safety, the most clinically relevant adverse effects are nephrotoxicity and neurotoxicity, which will be evaluated and adjudicated. The recurrence of infection will be defined as a new superinfection by the same or other species than the initial infection that is multidrug-resistant. Length of stay at the Hospital will be measured from the day of admission until the day of discharge. Length of stay in the ICU will be measured from the day of admission until the day of discharge from the unit. To our knowledge, this will be the first prospective, double blind, randomized, controlled clinical trial in representation of the critically ill trauma patients infected with Multi-drug resistant pathogens.

Study Type

Interventional

Enrollment (Anticipated)

40

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

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

21 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 21 years or older admitted to the Intensive Care Unit of the Puerto Rico Trauma Hospital ° Consent form signed,
  • Clinical and microbiological evidence of a MDR infection related to HAP, VAP, cUTI or BSI.
  • The pathogen should be resistant to almost all antibiotics, AND/OR intermediate resistant to some of the antibiotics, AND/OR susceptible only to a class of antibiotic (i.e. aminoglycosides which are NOT recommended as monotherapy), AND/OR the clinician decision is to start the patient on polymyxin B due to severity of the infection.
  • Patient with a diagnosis of MDR infection, who have not received antibiotics at all; OR if received would be < 72 hours with polymyxin B or imipenem at/or after the diagnosis of MDR AND/OR at the time of randomization
  • Have a life expectancy of > 24 hours according to the attending physician's criteria.

Exclusion Criteria:

  • Pregnant woman
  • Prisoners
  • Severe hepatic failure (defined by serum conjugated bilirubin > 3 mg/dL)
  • End-stage renal disease requiring hemodialysis
  • Hypersensitivity to any study drug
  • Septic shock at the moment of randomization
  • Died within 48 hours of starting the 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
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
OTHER: Polymyxin B monotherapy
Intravenous piggyback with Polymyxin B and control(Normal saline)
Drug: Polymyxin B
Comparison of Poly B monotherapy vs Polymyxin B plus carbapenem in MDR infections
Other Names:
  • Imipenem, (Primaxin)
EXPERIMENTAL: Polymyxin B plus Carbapenem
Intravenous piggyback with Polymyxin B plus Carbapenem
Drug: Polymyxin B
Comparison of Poly B monotherapy vs Polymyxin B plus carbapenem in MDR infections
Other Names:
  • Imipenem, (Primaxin)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Resolution of the evidence of clinical infection
Time Frame: 7-14 days, according to site of infection
Resolution of infection will be subjective to clinical criteria of the physician, AND patient has to be afebrile (temperature < 38°C), or normothermic (temperature 36-37.5°C), AND have white blood cell count within normal limits (> 4,000 and < 10,000 cells/mm3).
7-14 days, according to site of infection

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
30-day mortality
Time Frame: 30 days
Thirty-day (30-day) mortality will be measured from the day of hospital admission until discharge.
30 days
Recurrence of infection
Time Frame: 30 days
The recurrence of infection will be defined as a new superinfection by the same or other species than the initial infection that is multidrug-resistant.
30 days
Length of stay at Hospital
Time Frame: 30 days
Will be measured from the day of hospital admission until discharge.
30 days
Length of stay at ICU.
Time Frame: 30 days
Will be measured from the day of ICU admission until transfer or discharge.
30 days

Collaborators and Investigators

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

Sponsor

University of Puerto Rico

Investigators

  • Principal Investigator: Juan M Maldonado Lozada, PharmD, School of Pharmacy, University of Puerto Rico

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 (ACTUAL)

May 25, 2017

Primary Completion (ANTICIPATED)

December 1, 2019

Study Completion (ANTICIPATED)

December 1, 2019

Study Registration Dates

First Submitted

May 10, 2017

First Submitted That Met QC Criteria

May 17, 2017

First Posted (ACTUAL)

May 18, 2017

Study Record Updates

Last Update Posted (ACTUAL)

February 8, 2019

Last Update Submitted That Met QC Criteria

February 7, 2019

Last Verified

February 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • B1210116

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

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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