Efficacy of Polymyxin B Against Infections Caused by Extensively Drug-resistant (XDR) Gram-Negative Bacteria (XDR)

The objective of the study is to evaluate the efficacy of Polymyxin B for treatment Gram negative bacterial infection. The hypothesis of study is Polymyxin B would be the new antibacterial agents for Thai Gram negative infected patients in case of desirable outcomes and minimal side effects.

Study Overview

• Status: Unknown
• Conditions: Hospital Infection
• Intervention / Treatment: Drug: Polymyxin B

Detailed Description

• Investigator is notified by doctors who take care of gram negative infected patients.
• Investigator inform patient or their relatives about all topics in project, eligible criteria, method, material and monitoring treatment.
• After patient or their relatives are appreciated to join this project, investigator collect data in case record form;electronics form, then implement the drug.
• Duration of treatment is determined by site and severity of infection, approximately 7-14 days.
• Sample size calculation, by prevalence formula, we estimate the mortality rate about 50 %, deviation 10 %,and 2-sided 95% Confidence interval, therefore,97 persons
• We estimate gather data about 100 persons.
• Statistical descriptive analysis for descriptive data.
• During the study is performing, all unexpected adverse event definitely report to Siriraj institutional Review Board immediately, in addition to subjects or their relatives.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Thundon Ngamprasertchai, MD.; Phone Number: 66850887736; Email: thundon_ngamprasertchai@hotmail.com
• Study Contact Backup: Name: Adhiratha Boonyasiri, MD; Phone Number: 66850632181; Email: nonghor@yahoo.com

Study Locations

• Thailand
  • Bangkok, Thailand, 10700
    • Recruiting
    • Siriraj Hospital
    • Contact: Thundon Ngamprasertchai, MD; Phone Number: 66850887736; Email: thundon_ngamprasertchai@hotmail.com
    • Contact: Visanu Thamlikitkul, MD; Phone Number: 66818206271; Email: visanu.tha@mahidol.ac.th
    • Sub-Investigator: Adhiratha Boonyasiri, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18-75 year-old
• The infection caused by carbapenem-resistant (CR) Enterobacteriaceae, CR P.aeruginosa or CR A. baumannii which susceptible to colistin
• The duration of treatment approximately between 7-14 days
• Kidney function, according to Kidney Disease Improving Global Outcomes (KDIGO) classification, should less than stage 4 and no replacement therapy in all modality.
• The patients are anticipated to live more than 48 hrs after participation.
• In case of Colistin administration beforehand, it should not exceed 24 hrs.
• All of participants should be willing to join this project.

Exclusion Criteria:

• Pregnancy and lactation
• End stage renal disease who take renal replacement therapy
• Any type of Neuromuscular disease
• Body mass index exceed 30
• Infection that require treatment more than 14 days

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Polymyxin B; Polymyxin B 1.5-2.5 mg/kg/day intravenous q 12 hrs duration 7-14 days	Drug: Polymyxin B; administrate drug by 0.75-1.25 mg/kg/dose intravenously q 12 hrs both saline and dextrose solution can be dissolved duration 7-14 days; Other Names: X-Gen Phamaceuticals, USA Polymyxin B

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
mortality rate	mortality rate of gram negative bacteria infected patients receiving Polymyxin B at day 28 after enrollment	participants will be followed for the duration of hospital stay, an expected average of 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
adverse drug reactions	we assess adverse drug reactions in 2 aspects; nephrotoxicity and neurotoxicity	participants will be followed for the duration of hospital stay, an expected average of 4 weeks
microbiological clearance	we perform culture and staining to assess bacterial clearance after apply the study drug every 3 days until culture is negative	participants will be followed for the duration of hospital stay, an expected average of 4 weeks
Peak Plasma Concentration (Cmax) of polymyxin B	we do the blood test for drug level at before the third date dose then 1,2,4 hours after administration of the polymixin B and before the fourth dose.	participants will be followed for the duration of hospital stay, an expected average of 4 weeks

Collaborators and Investigators

• Sponsor: Mahidol University
• Investigators: Principal Investigator: Visanu Thamlikitkul, MD, Infectious disease and tropical medicine, Siriraj hospital

Publications and helpful links

General Publications

• Koomanachai P, Tiengrim S, Kiratisin P, Thamlikitkul V. Efficacy and safety of colistin (colistimethate sodium) for therapy of infections caused by multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii in Siriraj Hospital, Bangkok, Thailand. Int J Infect Dis. 2007 Sep;11(5):402-6. doi: 10.1016/j.ijid.2006.09.011. Epub 2007 Feb 8.
• Nation RL, Velkov T, Li J. Colistin and polymyxin B: peas in a pod, or chalk and cheese? Clin Infect Dis. 2014 Jul 1;59(1):88-94. doi: 10.1093/cid/ciu213. Epub 2014 Apr 3.

Helpful Links

• Centers for Disease Control (CDC) drug resistance 2013

Study record dates

Study Major Dates

• Study Start: December 1, 2014
• Primary Completion (Anticipated): November 1, 2015
• Study Completion (Anticipated): November 1, 2015

Study Registration Dates

• First Submitted: December 15, 2014
• First Submitted That Met QC Criteria: December 26, 2014
• First Posted (Estimate): December 31, 2014

Study Record Updates

• Last Update Posted (Estimate): September 1, 2015
• Last Update Submitted That Met QC Criteria: August 31, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: polymyxin B; carbapenem resistant bacteria
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Iatrogenic Disease; Infections; Communicable Diseases; Cross Infection; Anti-Infective Agents; Anti-Bacterial Agents; Polymyxins; Polymyxin B
• Other Study ID Numbers: 568/2557(EC4)