Standard vs. Biofilm Susceptibility Testing in Cystic Fibrosis (CF)

NCT00153634 | Completed DMC

• 1 other identifier: BURNS03A0
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 8

Brief Summary

This was a randomized multi-center clinical trial to compare the microbiological efficacy, clinical efficacy, and safety of using standard versus biofilm susceptibility testing of P. aeruginosa sputum isolates to guide antibiotic selection for treatment of airway infection in clinically stable patients with CF.

Conditions

Cystic Fibrosis; Chronic Bronchitis

Keywords

Cystic fibrosis; Antibiotic susceptibility testing; Pseudomonas aeruginosa; Chronic bronchitis; Biofilms

Outcome Measures

Primary Outcomes (1)

• Microbiological efficacy: Change in P. aeruginosa density

  from enrollment (up to day -21) to end of treatment (day 12-14)

Secondary Outcomes (3)

• Clinical efficacy: Pre- to post-treatment change in FEV1

  from initiation (day 0) to end of treatment (day 12-14)

• Safety: Adverse events, including new onset of acute pulmonary exacerbation and/or the need to change antibiotic therapy during the treatment period

  from enrollment (up to day -21) to end of treatment (day 12-14)

• Feasibility: Average costs and time per assay; rate of patient withdrawal because resistance patterns preclude randomization; self-reported technician satisfaction

  during active enrollment (March 2004-November 2007)

Study Arms (2)

1

EXPERIMENTAL

Antibiotic regimen assignment based on biofilm susceptibility test results

Drug: IV amikacin; Drug: PO azithromycin; Drug: IV ceftazidime; Drug: PO ciprofloxacin; Drug: IV meropenem; Drug: IV piperacillin-tazobactam; Drug: IV ticarcillin-clavulanate; Drug: IV tobramycin

2

ACTIVE COMPARATOR

Antibiotic regimen assignment based on conventional susceptibility test results

Drug: IV amikacin; Drug: PO azithromycin; Drug: IV ceftazidime; Drug: PO ciprofloxacin; Drug: IV meropenem; Drug: IV piperacillin-tazobactam; Drug: IV ticarcillin-clavulanate; Drug: IV tobramycin

Interventions

IV amikacin DRUG

5-7.5 mg/kg every 8 hrs or previous dose; start at previous recent stable dose then monitor serum levels and adjust dose, if needed, per standard clinical practice at the site

1; 2

PO azithromycin DRUG

250 mg once daily

1; 2

IV ceftazidime DRUG

50 mg/kg every 8 hours, up to 2 grams every 8 hours

1; 2

PO ciprofloxacin DRUG

500 mg every 12 hours if weight \<50 kg 750 mg every 12 hours if weight ≥50 kg

1; 2

IV meropenem DRUG

40 mg/kg every 8 hours, up to 2 grams every 8 hours

1; 2

IV piperacillin-tazobactam DRUG

100 mg/kg of piperacillin component every 6 hours, up to 3 grams every 6 hours; antibiotic combination formulated in a fixed ratio, thus dosing is described for first component only

1; 2

IV ticarcillin-clavulanate DRUG

100 mg/kg of ticarcillin component every 6 hours, up to 3 grams every 6 hours; antibiotic combination formulated in a fixed ratio, thus dosing is described for first component only

1; 2

IV tobramycin DRUG

2.5-3.3 mg/kg every 8 hrs or previous dose; start at previous recent stable dose then monitor serum levels and adjust dose, if needed, per standard clinical practice at the site

1; 2

Eligibility Criteria

• Age: 14 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of CF based on the following: sweat chloride \> 60 mEq/L (by quantitative pilocarpine iontophoresis), or genotype with 2 identifiable mutations consistent with CF; and one or more clinical features consistent with CF.
• Age ≥ 14 years (changed from ≥ 18 years by protocol amendment).
• Able to expectorate sputum at screening.
• History of persistent positivity for P. aeruginosa on respiratory culture (at least three positive oropharyngeal (OP), sputum and/or bronchoscopy cultures in the 24 months prior to screening).
• Able to reproducibly perform pulmonary function testing.
• Clinically stable at screening, with no evidence of pulmonary exacerbation.
• Written informed consent provided.

You may not qualify if:

• Sputum culture negative for P. aeruginosa or density less than 10E5 CFU/gm at screening.
• Sputum culture positive for B. cepacia at screening.
• Presence of P. aeruginosa in sputum with off-scale resistance to all antibiotics by either method of susceptibility testing at screening. (changed from multiply-resistant P. aeruginosa by protocol amendment)
• History of B. cepacia positive respiratory culture within 24 months prior to screening.
• Hospitalization or treatment for a pulmonary exacerbation within 2 months prior to screening.
• Administration of parenteral anti-pseudomonal antibiotics within 2 months prior to screening.
• Treatment with oral or inhaled anti-pseudomonal antibiotics, or azithromycin or other macrolides within 14 days prior to screening.
• History of allergy (urticarial rash, diffuse erythroderma, serum sickness) to more than two groups of antibiotics (aminoglycosides, penicillins, cephalosporins, monobactams, macrolides, or quinolones) that are a therapeutic option.
• History of anaphylaxis or other life threatening complication to any antibiotic in the six groups that are a therapeutic option.
• History of abnormal renal function (serum creatinine \> 1.5 x upper limit of normal) within one year of enrollment.
• History of abnormal liver function tests (\> 2.5 x upper limit of normal) within one year of enrollment.
• Clinically documented hearing loss that precludes treatment with aminoglycosides.
• Post lung transplantation.
• Positive pregnancy test or female who is lactating or is not practicing an acceptable method of birth control.
• Presence of a condition or abnormality that in the opinion of an investigator would compromise the safety of the patient or the quality of the data.

Sponsors & Collaborators

• Seattle Children's Hospital: lead
• Cystic Fibrosis Foundation: collaborator

Study Sites (8)

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Washington University St. Louis

St Louis, Missouri, 63110, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267-0557, United States

Location

Ohio State University

Columbus, Ohio, 43205, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Children's Hospital and Regional Medical Center

Seattle, Washington, 98105-0371, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

Related Publications (2)

• Moskowitz SM, Foster JM, Emerson J, Burns JL. Clinically feasible biofilm susceptibility assay for isolates of Pseudomonas aeruginosa from patients with cystic fibrosis. J Clin Microbiol. 2004 May;42(5):1915-22. doi: 10.1128/JCM.42.5.1915-1922.2004.

  PMID: 15131149 BACKGROUND

• Moskowitz SM, Foster JM, Emerson JC, Gibson RL, Burns JL. Use of Pseudomonas biofilm susceptibilities to assign simulated antibiotic regimens for cystic fibrosis airway infection. J Antimicrob Chemother. 2005 Nov;56(5):879-86. doi: 10.1093/jac/dki338. Epub 2005 Sep 27.

  PMID: 16188918 BACKGROUND

MeSH Terms

Conditions

Cystic Fibrosis; Bronchitis, Chronic; Pseudomonas Infections

Interventions

Amikacin; Ceftazidime; Meropenem; Piperacillin, Tazobactam Drug Combination; ticarcillin-clavulanic acid; Tobramycin

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; Bronchitis; Respiratory Tract Infections; Infections; Bronchial Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses

Intervention Hierarchy (Ancestors)

Kanamycin; Aminoglycosides; Glycosides; Carbohydrates; Cephaloridine; Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Thienamycins; Carbapenems; Tazobactam; Penicillanic Acid; Penicillins; Piperacillin; Ampicillin; Penicillin G; Sulfones; Drug Combinations; Pharmaceutical Preparations; Nebramycin

Study Officials

• Samuel M Moskowitz, MD

  Seattle Children's Hospital

  PRINCIPAL INVESTIGATOR

• Jane L Burns, MD

  Children's Hospital and Regional Medical Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 8, 2005
• First Posted: September 12, 2005
• Study Start: March 1, 2004
• Study Completion: November 1, 2007
• Last Updated: March 13, 2008

Record last verified: 2007-11

Locations

US (8)