Clinical trial NCT01509339: Pharmacokinetics of Vancomycin for Inhalation in Cystic Fibrosis
Official title: Pharmacokinetics of Vancomycin for Inhalation in Cystic Fibrosis
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Cystic Fibrosis
Methicillin-resistant Staphylococcus Aureus
Keywords: Vancomycin
Inhalation
Nebulization
Pharmacokinetics
Lead sponsor: Case Western Reserve University
Sponsor class: OTHER
Collaborators: name: Cystic Fibrosis Foundation
First posted: 2012-01-13
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Area Under Curve (AUC)
timeFrame: Predose, 5 minutes, one hour, 2 hours, and 6 hours after completion of 250mg of inhaled vancomycin
Secondary outcomes:
measure: Change in FEV1% Predicted
timeFrame: 30 minutes
measure: Change in Patient Symptoms
timeFrame: 6 hours
measure: Change in Sputum Cell Counts
timeFrame: 6 hours
measure: Serum Vancomycin Peak Concentration
timeFrame: 60 minutes
measure: Oxygen Saturation
timeFrame: 5 minutes
measure: Adverse Events
timeFrame: 6 hours
measure: Maximum Concentration
timeFrame: Predose, 5 minutes, one hour, 2 hours, and 6 hours after completion of 250mg of inhaled vancomycin
measure: Time to Peak Concentration
timeFrame: Predose, 5 minutes, one hour, 2 hours, and 6 hours after completion of 250mg of inhaled vancomycin
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Rainbow Babies and Children's Hospital, Univeristy Hospitals Case Medical Center
state: Ohio
Study officials:
affiliation: Case Western Reserve University School of Medicine
name: Elliott C Dasenbrook, MD MHS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dasenbrook EC, Checkley W, Merlo CA, Konstan MW, Lechtzin N, Boyle MP. Association between respiratory tract methicillin-resistant Staphylococcus aureus and survival in cystic fibrosis. JAMA. 2010 Jun 16;303(23):2386-92. doi: 10.1001/jama.2010.791.
citation: Dasenbrook EC, Merlo CA, Diener-West M, Lechtzin N, Boyle MP. Persistent methicillin-resistant Staphylococcus aureus and rate of FEV1 decline in cystic fibrosis. Am J Respir Crit Care Med. 2008 Oct 15;178(8):814-21. doi: 10.1164/rccm.200802-327OC. Epub 2008 Jul 31.
citation: Dasenbrook EC. Update on methicillin-resistant Staphylococcus aureus in cystic fibrosis. Curr Opin Pulm Med. 2011 Nov;17(6):437-41. doi: 10.1097/MCP.0b013e32834b95ed.
citation: Doe SJ, McSorley A, Isalska B, Kearns AM, Bright-Thomas R, Brennan AL, Webb AK, Jones AM. Patient segregation and aggressive antibiotic eradication therapy can control methicillin-resistant Staphylococcus aureus at large cystic fibrosis centres. J Cyst Fibros. 2010 Mar;9(2):104-9. doi: 10.1016/j.jcf.2009.11.009. Epub 2010 Jan 3.