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

NCT03159078 | Unknown Phase 3 FDA Drug

• 1 other identifier: B1210116
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Trauma; Resistant Infection; Critical Illness

Keywords

Acinetobacter; Polymyxins; Imipenem; Pseudomona; Klebsiella

Outcome Measures

Primary Outcomes (1)

• Resolution of the evidence of clinical 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 Outcomes (4)

• 30-day mortality

  30 days

• Recurrence of infection

  30 days

• Length of stay at Hospital

  30 days

• Length of stay at ICU.

  30 days

Study Arms (2)

Polymyxin B monotherapy

OTHER

Intravenous piggyback with Polymyxin B and control(Normal saline)

Drug: Polymyxin B

Polymyxin B plus Carbapenem

EXPERIMENTAL

Intravenous piggyback with Polymyxin B plus Carbapenem

Drug: Polymyxin B

Interventions

Polymyxin B DRUG

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

Also known as: Imipenem, (Primaxin)

Polymyxin B monotherapy; Polymyxin B plus Carbapenem

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Puerto Rico: lead

Study Sites (1)

Trauma Hospital

San Juan, 00922-2129, Puerto Rico

RECRUITING

Related Publications (21)

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• Tumbarello M, Viale P, Viscoli C, Trecarichi EM, Tumietto F, Marchese A, Spanu T, Ambretti S, Ginocchio F, Cristini F, Losito AR, Tedeschi S, Cauda R, Bassetti M. Predictors of mortality in bloodstream infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae: importance of combination therapy. Clin Infect Dis. 2012 Oct;55(7):943-50. doi: 10.1093/cid/cis588. Epub 2012 Jul 2.

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Related Links

• Trial for the Treatment of Extensively Drug-Resistant Gram-negative Bacilli
• Multicenter Open-label Randomized Controlled Trial (RCT) to Compare Colistin Alone Versus Colistin Plus Meropenem
• Primaxin I.V. (Imipenem and Cilastatin for IV Injection).

MeSH Terms

Conditions

Wounds and Injuries; Critical Illness; Pseudomonas Infections; Klebsiella Infections

Interventions

Polymyxin B; Imipenem; Cilastatin, Imipenem Drug Combination

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Enterobacteriaceae Infections

Intervention Hierarchy (Ancestors)

Polymyxins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Lipopeptides; Lipids; Antimicrobial Cationic Peptides; Peptides; Amino Acids, Peptides, and Proteins; Antimicrobial Peptides; Pore Forming Cytotoxic Proteins; Membrane Proteins; Proteins; Thienamycins; Carbapenems; beta-Lactams; Lactams; Amides; Organic Chemicals; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Cilastatin; Cyclopropanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Fatty Acids, Monounsaturated; Fatty Acids, Unsaturated; Fatty Acids; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Juan M Maldonado Lozada, PharmD

  School of Pharmacy, University of Puerto Rico

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Juan M Maldonado Lozada, Pharm D

CONTACT

7875570612; juan.maldonado12@upr.edu

Pablo Rodriguez, MD

CONTACT

787430-4415; pablororc@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double blind, Double dummy
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: One arm with Polyxyxin B monotherapy and another arm with Polymyxin B plus carbapenem

Study Record Dates

• First Submitted: May 10, 2017
• First Posted: May 18, 2017
• Study Start: May 25, 2017
• Primary Completion: December 1, 2019
• Study Completion: December 1, 2019
• Last Updated: February 8, 2019

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will not share

Locations

PR (1)