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

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ClinicalTrials.gov Identifier: NCT03159078
Recruitment Status : Recruiting
First Posted : May 18, 2017
Last Update Posted : February 8, 2019
Sponsor:
Information provided by (Responsible Party):
University of Puerto Rico

Tracking Information
First Submitted Date  ICMJE May 10, 2017
First Posted Date  ICMJE May 18, 2017
Last Update Posted Date February 8, 2019
Actual Study Start Date  ICMJE May 25, 2017
Estimated Primary Completion Date December 1, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 17, 2017)
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).
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03159078 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 17, 2017)
  • 30-day mortality [ Time Frame: 30 days ]
    Thirty-day (30-day) mortality will be measured from the day of hospital admission until discharge.
  • 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.
  • Length of stay at Hospital [ Time Frame: 30 days ]
    Will be measured from the day of hospital admission until discharge.
  • Length of stay at ICU. [ Time Frame: 30 days ]
    Will be measured from the day of ICU admission until transfer or discharge.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Polymyxin B Monotherapy vs Combination Therapy in Critically Ill Patients With Multi-drug Resistant Pathogens
Official Title  ICMJE 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
Brief Summary 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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
One arm with Polyxyxin B monotherapy and another arm with Polymyxin B plus carbapenem
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description:
Double blind, Double dummy
Primary Purpose: Treatment
Condition  ICMJE
  • Trauma
  • Resistant Infection
  • Critical Illness
Intervention  ICMJE Drug: Polymyxin B
Comparison of Poly B monotherapy vs Polymyxin B plus carbapenem in MDR infections
Other Name: Imipenem, (Primaxin)
Study Arms  ICMJE
  • Polymyxin B monotherapy
    Intravenous piggyback with Polymyxin B and control(Normal saline)
    Intervention: Drug: Polymyxin B
  • Experimental: Polymyxin B plus Carbapenem
    Intravenous piggyback with Polymyxin B plus Carbapenem
    Intervention: Drug: Polymyxin B
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 17, 2017)
40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 1, 2019
Estimated Primary Completion Date December 1, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Juan M Maldonado Lozada, Pharm D 7875570612 juan.maldonado12@upr.edu
Contact: Pablo Rodriguez, MD 787430-4415 pablororc@gmail.com
Listed Location Countries  ICMJE Puerto Rico
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03159078
Other Study ID Numbers  ICMJE B1210116
Has Data Monitoring Committee No
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University of Puerto Rico
Study Sponsor  ICMJE University of Puerto Rico
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Juan M Maldonado Lozada, PharmD School of Pharmacy, University of Puerto Rico
PRS Account University of Puerto Rico
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP