Pharmacokinetics of Vancomycin for Inhalation in Cystic Fibrosis

Phase 1

Withdrawn

• Conditions: Cystic Fibrosis; Methicillin-resistant Staphylococcus Aureus
• Interventions: Drug: Vancomycin

• Registration Number: NCT01509339
• Lead Sponsor: Case Western Reserve University

Brief Summary

The purpose of this study is to determine the pharmacokinetics and safety of inhaled vancomycin in patients with cystic fibrosis.

Detailed Description

The prevalence of methicillin resistant Staphylococcus aureus (MRSA) respiratory infection in patients with cystic fibrosis has increased dramatically over the last decade. Epidemiologic evidence suggests that persistent infection with MRSA may result in an increased rate of decline in FEV1 and shortened survival. Treatment of MRSA is a top priority. Inhaled antibiotics offer the advantage of high concentrations of antibiotic at the site of infection (the airway) while minimizing systemic side effects. Vancomycin is a glycopeptide antibiotic that has activity against MRSA. Anecdotal and retrospective peer-reviewed studies have demonstrated that inhaled vancomycin is safe and potentially effective in patients with cystic fibrosis and MRSA airway infection. Data evaluating the pharmacokinetics of vancomycin in sputum are needed before pursuing treatment trials.

Study Timeline

• Study Start: 2012-01
• Study First Submitted: 2012-01-09
• Study First Submitted QC: 2012-01-10
• Study First Posted: 2012-01-13
• Status Verified: 2021-12
• Primary Completion: 2021-12-23
• Study Completion: 2021-12-23
• Last Update Submitted: 2021-12-23
• Last Update Posted: 2022-01-12

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

• Male or female ≥ 18 years of age.

• Confirmed diagnosis of CF based on the following criteria:

  • positive sweat chloride > 60 mEq/liter (by pilocarpine iontophoresis) and/or
  • a genotype with two identifiable mutations consistent with CF or abnormal NPD, and
  • one or more clinical features consistent with the CF phenotype.

• Chronic sputum producer able to spontaneously produce sputum

• FEV1 > 40% of predicted normal for age, gender, and height

• Previous use of any inhaled antibiotics within the last year

• Ability to provide written informed consent

• Ability to adhere to the protocol

Exclusion Criteria

• Use of inhaled or intravenous vancomycin within two weeks of the study visit
• Known history of intolerance to inhaled vancomycin or inhaled albuterol.
• Known history of hypersensitivity to vancomycin or other glycopeptide antibiotics
• History of sputum culture with Burkholderia cepacia complex in the last two years.
• Pregnancy
• Woman who are lactating and not willing to stop nursing on the day of the study visit and the subsequent 48 hours.
• Current use of oral corticosteroids in doses exceeding the equivalent of 10mg of prednisone a day or 20mg of prednisone every other day.
• Patients not willing to hold other inhaled antibiotics (for example TOBI, Cayston, or Colistin) for at least 2 days prior to the study visit.
• Patients not willing to hold loop diuretics (i.e. furosemide, torsemide, ethacrynic acid) on the morning of the study visit.
• History of ABPA or reactive airways disease that has required treatment within the last year.
• Creatinine greater than 2.0 mg/dL within the last year.
• Oxygen saturation ≤ 92% on room air.
• History of patient reported hearing loss
• Any serious or active medical or psychiatric illness, which in the opinion of the investigator, would interfere with patient treatment, assessment, or adherence to the protocol.
• History of or listed for solid organ or hematological transplantation

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Vancomycin for Inhalation	Vancomycin	250 mg vancomycin in 5cc sterile water will be inhaled once. Patients will use a Pari Sprint nebulizer and Pari Vios compressor as the delivery system.

Primary Outcome Measures

Name	Time	Method
Area Under Curve (AUC)	Predose, 5 minutes, one hour, 2 hours, and 6 hours after completion of 250mg of inhaled vancomycin	Pharmacokinetic analysis will be performed with non-compartmental methods. The area under the curve for sputum vancomycin will be determined.

Secondary Outcome Measures

Name	Time	Method
Change in Sputum Cell Counts	6 hours	Change in sputum cell counts (i.e. eosinophils) between baseline and six hours after completion of inhaled vancomycin.
Change in FEV1% Predicted	30 minutes	Change in FEV1% predicted from baseline to 30 minutes after completion of inhaled vancomycin
Serum Vancomycin Peak Concentration	60 minutes	Serum vancomycin peak concentration 60 minutes after completion of inhaled vancomycin.
Change in Patient Symptoms	6 hours	Patient's respiratory symptoms and potential side effects from inhaling vancomycin will be queried using a questionnaire prior to inhaling vancomycin, at 15 ±10 minutes, and 4 ± 1 hour after completing inhaled vancomycin.
Oxygen Saturation	5 minutes	Continuous oxygen saturation monitoring to be continued throughout vancomycin inhalation and for 5 minutes after inhalation
Adverse Events	6 hours	Information regarding occurrence of adverse events will be captured throughout the study. Duration (start and stop times), severity/grade, outcome, treatment and relation to study medication will be recorded
Time to Peak Concentration	Predose, 5 minutes, one hour, 2 hours, and 6 hours after completion of 250mg of inhaled vancomycin	Pharmacokinetic analysis will be performed with non-compartmental methods. The time to peak concentration for sputum vancomycin will be determined.
Maximum Concentration	Predose, 5 minutes, one hour, 2 hours, and 6 hours after completion of 250mg of inhaled vancomycin	Pharmacokinetic analysis will be performed with non-compartmental methods. The maximum concentration of sputum vancomycin will be determined.

Trial Locations

Locations (1)

Rainbow Babies and Children's Hospital, Univeristy Hospitals Case Medical Center; 🇺🇸 Cleveland, Ohio, United States