Pharmacokinetics of Vancomycin for Inhalation in Cystic Fibrosis

Case Western Reserve University

Status and phase: Withdrawn; Phase 1

Conditions: Methicillin-resistant Staphylococcus Aureus; Cystic Fibrosis

Treatments: Drug: Vancomycin

Study type: Interventional

Funder types: Other

Identifiers

NCT01509339

iVCM 1.0

Details and patient eligibility

About

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

Full 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.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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0 participants in 1 patient group

Vancomycin for Inhalation

Experimental group

Description:

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.

Treatment:

Drug: Vancomycin