Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
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

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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.

Condition or disease Intervention/treatment Phase
Trauma Resistant Infection Critical Illness Drug: Polymyxin B Phase 3

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 Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
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
Official Title: 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
Actual Study Start Date : May 25, 2017
Estimated Primary Completion Date : December 1, 2019
Estimated Study Completion Date : December 1, 2019

Resource links provided by the National Library of Medicine


Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
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 Name: 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 Name: Imipenem, (Primaxin)


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. 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).


Secondary Outcome Measures :
  1. 30-day mortality [ Time Frame: 30 days ]
    Thirty-day (30-day) mortality will be measured from the day of hospital admission until discharge.

  2. 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.

  3. Length of stay at Hospital [ Time Frame: 30 days ]
    Will be measured from the day of hospital admission until discharge.

  4. Length of stay at ICU. [ Time Frame: 30 days ]
    Will be measured from the day of ICU admission until transfer or discharge.


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   21 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03159078


Contacts
Layout table for location contacts
Contact: Juan M Maldonado Lozada, Pharm D 7875570612 juan.maldonado12@upr.edu
Contact: Pablo Rodriguez, MD 787430-4415 pablororc@gmail.com

Locations
Layout table for location information
Puerto Rico
Trauma Hospital Recruiting
San Juan, Puerto Rico, 00922-2129
Contact: Juan M Maldonado, Pharm D    787-557-0612    juan.maldonado12@upr.edu   
Contact: Pablo Rodriguez, MD    787-4304415    pablororc@gmail.com   
Sponsors and Collaborators
University of Puerto Rico
Investigators
Layout table for investigator information
Principal Investigator: Juan M Maldonado Lozada, PharmD School of Pharmacy, University of Puerto Rico
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:
Type of Healthcare-Associated Infections  This link exits the ClinicalTrials.gov site Gram-negative Bacteria Infections in Healthcare Settings  This link exits the ClinicalTrials.gov site Trial for the Treatment of Extensively Drug-Resistant Gram-negative Bacilli  This link exits the ClinicalTrials.gov site Multicenter Open-label Randomized Controlled Trial (RCT) to Compare Colistin Alone Versus Colistin Plus Meropenem  This link exits the ClinicalTrials.gov site Primaxin I.V. (Imipenem and Cilastatin for IV Injection).  This link exits the ClinicalTrials.gov site Antibiotic resistance threats in the United States  This link exits the ClinicalTrials.gov site Performance standards for antimicrobial susceptibility testing: twenty-six informational supplement.  This link exits the ClinicalTrials.gov site

Publications of Results:

Layout table for additonal information
Responsible Party: University of Puerto Rico
ClinicalTrials.gov Identifier: NCT03159078     History of Changes
Other Study ID Numbers: B1210116
First Posted: May 18, 2017    Key Record Dates
Last Update Posted: February 8, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
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
Keywords provided by University of Puerto Rico:
Acinetobacter
Polymyxins
Imipenem
Pseudomona
Klebsiella
Additional relevant MeSH terms:
Layout table for MeSH terms
Infection
Critical Illness
Disease Attributes
Pathologic Processes
Imipenem
 Polymyxins
Polymyxin B
Anti-Bacterial Agents
Anti-Infective Agents