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Pharmacokinetics of Vancomycin for Inhalation in Cystic Fibrosis

Primary Purpose

Cystic Fibrosis, Methicillin-resistant Staphylococcus Aureus

Status
Withdrawn
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Vancomycin
Sponsored by
Case Western Reserve University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cystic Fibrosis focused on measuring Vancomycin, Inhalation, Nebulization, Pharmacokinetics

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Rainbow Babies and Children's Hospital, Univeristy Hospitals Case Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Vancomycin for Inhalation

Arm 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.

Outcomes

Primary Outcome Measures

Area Under Curve (AUC)
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
Change in FEV1% predicted from baseline to 30 minutes after completion of inhaled vancomycin
Change in Patient Symptoms
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
Change in sputum cell counts (i.e. eosinophils) between baseline and six hours after completion of inhaled vancomycin.
Serum Vancomycin Peak Concentration
Serum vancomycin peak concentration 60 minutes after completion of inhaled vancomycin.
Oxygen Saturation
Continuous oxygen saturation monitoring to be continued throughout vancomycin inhalation and for 5 minutes after inhalation
Adverse Events
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
Pharmacokinetic analysis will be performed with non-compartmental methods. The maximum concentration of sputum vancomycin will be determined.
Time to Peak Concentration
Pharmacokinetic analysis will be performed with non-compartmental methods. The time to peak concentration for sputum vancomycin will be determined.

Full Information

First Posted
January 9, 2012
Last Updated
December 23, 2021
Sponsor
Case Western Reserve University
Collaborators
Cystic Fibrosis Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT01509339
Brief Title
Pharmacokinetics of Vancomycin for Inhalation in Cystic Fibrosis
Official Title
Pharmacokinetics of Vancomycin for Inhalation in Cystic Fibrosis
Study Type
Interventional

2. Study Status

Record Verification Date
December 2021
Overall Recruitment Status
Withdrawn
Why Stopped
Lab unable to measure vancomycin levels in Sputum
Study Start Date
January 2012 (Anticipated)
Primary Completion Date
December 23, 2021 (Actual)
Study Completion Date
December 23, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Case Western Reserve University
Collaborators
Cystic Fibrosis Foundation

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis, Methicillin-resistant Staphylococcus Aureus
Keywords
Vancomycin, Inhalation, Nebulization, Pharmacokinetics

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Vancomycin for Inhalation
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Vancomycin
Other Intervention Name(s)
Nebulized vancomycin, Inhaled Vancomycin, Vancomycin for inhalation, Aerosolized Vancomycin
Intervention 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.
Primary Outcome Measure Information:
Title
Area Under Curve (AUC)
Description
Pharmacokinetic analysis will be performed with non-compartmental methods. The area under the curve for sputum vancomycin will be determined.
Time Frame
Predose, 5 minutes, one hour, 2 hours, and 6 hours after completion of 250mg of inhaled vancomycin
Secondary Outcome Measure Information:
Title
Change in FEV1% Predicted
Description
Change in FEV1% predicted from baseline to 30 minutes after completion of inhaled vancomycin
Time Frame
30 minutes
Title
Change in Patient Symptoms
Description
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.
Time Frame
6 hours
Title
Change in Sputum Cell Counts
Description
Change in sputum cell counts (i.e. eosinophils) between baseline and six hours after completion of inhaled vancomycin.
Time Frame
6 hours
Title
Serum Vancomycin Peak Concentration
Description
Serum vancomycin peak concentration 60 minutes after completion of inhaled vancomycin.
Time Frame
60 minutes
Title
Oxygen Saturation
Description
Continuous oxygen saturation monitoring to be continued throughout vancomycin inhalation and for 5 minutes after inhalation
Time Frame
5 minutes
Title
Adverse Events
Description
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 Frame
6 hours
Title
Maximum Concentration
Description
Pharmacokinetic analysis will be performed with non-compartmental methods. The maximum concentration of sputum vancomycin will be determined.
Time Frame
Predose, 5 minutes, one hour, 2 hours, and 6 hours after completion of 250mg of inhaled vancomycin
Title
Time to Peak Concentration
Description
Pharmacokinetic analysis will be performed with non-compartmental methods. The time to peak concentration for sputum vancomycin will be determined.
Time Frame
Predose, 5 minutes, one hour, 2 hours, and 6 hours after completion of 250mg of inhaled vancomycin

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Elliott C Dasenbrook, MD MHS
Organizational Affiliation
Case Western Reserve University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Rainbow Babies and Children's Hospital, Univeristy Hospitals Case Medical Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
20551409
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.
Results Reference
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PubMed Identifier
18669817
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.
Results Reference
background
PubMed Identifier
21918450
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.
Results Reference
background
PubMed Identifier
20051329
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.
Results Reference
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Pharmacokinetics of Vancomycin for Inhalation in Cystic Fibrosis

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