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

NCT ID: NCT03159078

Last Updated: 2019-02-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-05-25

Study Completion Date

2019-12-01

Brief Summary

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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

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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.

Conditions

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Trauma Resistant Infection Critical Illness

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

One arm with Polyxyxin B monotherapy and another arm with Polymyxin B plus carbapenem
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators
Double blind, Double dummy

Study Groups

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Polymyxin B monotherapy

Intravenous piggyback with Polymyxin B and control(Normal saline)

Group Type OTHER

Polymyxin B

Intervention Type DRUG

Comparison of Poly B monotherapy vs Polymyxin B plus carbapenem in MDR infections

Polymyxin B plus Carbapenem

Intravenous piggyback with Polymyxin B plus Carbapenem

Group Type EXPERIMENTAL

Polymyxin B

Intervention Type DRUG

Comparison of Poly B monotherapy vs Polymyxin B plus carbapenem in MDR infections

Interventions

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Polymyxin B

Comparison of Poly B monotherapy vs Polymyxin B plus carbapenem in MDR infections

Intervention Type DRUG

Other Intervention Names

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Imipenem, (Primaxin)

Eligibility Criteria

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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
Minimum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Puerto Rico

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Juan M Maldonado Lozada, PharmD

Role: PRINCIPAL_INVESTIGATOR

School of Pharmacy, University of Puerto Rico

Locations

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Trauma Hospital

San Juan, , Puerto Rico

Site Status RECRUITING

Countries

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Puerto Rico

Central Contacts

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Juan M Maldonado Lozada, Pharm D

Role: CONTACT

7875570612

Pablo Rodriguez, MD

Role: CONTACT

787430-4415

Facility Contacts

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Juan M Maldonado, Pharm D

Role: primary

787-557-0612

Pablo Rodriguez, MD

Role: backup

787-4304415

References

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Related Links

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https://clinicaltrials.gov/ct2/show/record/nct01597973?term=nct01597973&rank=1

Trial for the Treatment of Extensively Drug-Resistant Gram-negative Bacilli

https://clinicaltrials.gov/ct2/show/record/nct01732250?term=nct01732250&rank=1

Multicenter Open-label Randomized Controlled Trial (RCT) to Compare Colistin Alone Versus Colistin Plus Meropenem

https://www.merck.com/product/usa/pi_circulars/p/primaxin/primaxin_iv_pi.pdf

Primaxin I.V. (Imipenem and Cilastatin for IV Injection).

Other Identifiers

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B1210116

Identifier Type: -

Identifier Source: org_study_id

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