Pharmacokinetics of Vancomycin for Inhalation in Cystic Fibrosis - Full Text View

Purpose

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

Condition	Intervention	Phase
Cystic Fibrosis Methicillin-resistant Staphylococcus Aureus	Drug: Vancomycin	Phase 1

Study Type:	Interventional
Study Design:	Endpoint Classification: Pharmacokinetics Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Pharmacokinetics of Vancomycin for Inhalation in Cystic Fibrosis

Resource links provided by NLM:

Genetics Home Reference related topics: cystic fibrosis

MedlinePlus related topics: Cystic Fibrosis

Drug Information available for: Vancomycin Vancomycin hydrochloride

U.S. FDA Resources

Further study details as provided by Case Western Reserve University:

Primary Outcome Measures:

Area Under Curve (AUC) [ Time Frame: Predose, 5 minutes, one hour, 2 hours, and 6 hours after completion of 250mg of inhaled vancomycin ] [ Designated as safety issue: No ]
Pharmacokinetic analysis will be performed with non-compartmental methods. The area under the curve for sputum vancomycin will be determined.

Secondary Outcome Measures:

Change in FEV1% Predicted [ Time Frame: 30 minutes ] [ Designated as safety issue: Yes ]
Change in FEV1% predicted from baseline to 30 minutes after completion of inhaled vancomycin
Change in Patient Symptoms [ Time Frame: 6 hours ] [ Designated as safety issue: Yes ]
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.
Change in Sputum Cell Counts [ Time Frame: 6 hours ] [ Designated as safety issue: Yes ]
Change in sputum cell counts (i.e. eosinophils) between baseline and six hours after completion of inhaled vancomycin.
Serum Vancomycin Peak Concentration [ Time Frame: 60 minutes ] [ Designated as safety issue: Yes ]
Serum vancomycin peak concentration 60 minutes after completion of inhaled vancomycin.
Oxygen Saturation [ Time Frame: 5 minutes ] [ Designated as safety issue: Yes ]
Continuous oxygen saturation monitoring to be continued throughout vancomycin inhalation and for 5 minutes after inhalation
Adverse Events [ Time Frame: 6 hours ] [ Designated as safety issue: Yes ]
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
Maximum Concentration [ Time Frame: Predose, 5 minutes, one hour, 2 hours, and 6 hours after completion of 250mg of inhaled vancomycin ] [ Designated as safety issue: No ]
Pharmacokinetic analysis will be performed with non-compartmental methods. The maximum concentration of sputum vancomycin will be determined.
Time to Peak Concentration [ Time Frame: Predose, 5 minutes, one hour, 2 hours, and 6 hours after completion of 250mg of inhaled vancomycin ] [ Designated as safety issue: No ]
Pharmacokinetic analysis will be performed with non-compartmental methods. The time to peak concentration for sputum vancomycin will be determined.

Estimated Enrollment:	10
Study Start Date:	January 2012
Estimated Study Completion Date:	May 2013
Estimated Primary Completion Date:	May 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Vancomycin for Inhalation 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.	Drug: 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. Other Names: Nebulized vancomycin Inhaled Vancomycin Vancomycin for inhalation Aerosolized Vancomycin

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01509339

Locations

United States, Ohio
Rainbow Babies and Children's Hospital, Univeristy Hospitals Case Medical Center
Cleveland, Ohio, United States, 44106

Sponsors and Collaborators

Case Western Reserve University

Cystic Fibrosis Foundation

Investigators

Principal Investigator:

Elliott C Dasenbrook, MD MHS

Case Western Reserve University School of Medicine

More Information

Publications:

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.

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. Epub 2008 Jul 31.

Dasenbrook EC. Update on methicillin-resistant Staphylococcus aureus in cystic fibrosis. Curr Opin Pulm Med. 2011 Nov;17(6):437-41. Review.

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. Epub 2010 Jan 3.

Responsible Party:	Elliott Dasenbrook, Assistant Professor of Medicine and Pediatrics, Case Western Reserve University
ClinicalTrials.gov Identifier:	NCT01509339 History of Changes
Other Study ID Numbers:	iVCM 1.0
Study First Received:	January 9, 2012
Last Updated:	January 25, 2013
Health Authority:	United States: Institutional Review Board

Keywords provided by Case Western Reserve University:

Vancomycin
Inhalation
Nebulization
Pharmacokinetics

Additional relevant MeSH terms:

Respiratory Aspiration
Cystic Fibrosis
Fibrosis
Staphylococcal Infections
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Pancreatic Diseases
Digestive System Diseases
Lung Diseases

Genetic Diseases, Inborn
Infant, Newborn, Diseases
Pathologic Processes
Gram-Positive Bacterial Infections
Bacterial Infections
Vancomycin
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 16, 2013