Pharmacokinetics of Vancomycin for Inhalation in Cystic Fibrosis

NCT01509339 | Withdrawn Phase 1 DMC

• 1 other identifier: iVCM 1.0
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Cystic Fibrosis; Methicillin-resistant Staphylococcus Aureus

Keywords

Vancomycin; Inhalation; Nebulization; Pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• Area Under Curve (AUC)

  Pharmacokinetic analysis will be performed with non-compartmental methods. The area under the curve for sputum vancomycin will be determined.

  Predose, 5 minutes, one hour, 2 hours, and 6 hours after completion of 250mg of inhaled vancomycin

Secondary Outcomes (8)

• Change in FEV1% Predicted

  30 minutes

• Change in Patient Symptoms

  6 hours

• Change in Sputum Cell Counts

  6 hours

• Serum Vancomycin Peak Concentration

  60 minutes

• Oxygen Saturation

  5 minutes

Study Arms (1)

Vancomycin for Inhalation

EXPERIMENTAL

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

Interventions

Vancomycin DRUG

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.

Also known as: Nebulized vancomycin, Inhaled Vancomycin, Vancomycin for inhalation, Aerosolized Vancomycin

Vancomycin for Inhalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Case Western Reserve University: lead
• Cystic Fibrosis Foundation: collaborator

Study Sites (1)

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

Cleveland, Ohio, 44106, United States

Location

Related Publications (4)

• 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.

  PMID: 20551409 BACKGROUND

• 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.

  PMID: 18669817 BACKGROUND

• 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.

  PMID: 21918450 BACKGROUND

• 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.

  PMID: 20051329 BACKGROUND

MeSH Terms

Conditions

Cystic Fibrosis; Respiratory Aspiration

Interventions

Vancomycin; Inhalation

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; Respiration Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins; Respiratory Mechanics; Respiration; Respiratory Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena

Study Officials

• Elliott C Dasenbrook, MD MHS

  Case Western Reserve University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine and Pediatrics

Study Record Dates

• First Submitted: January 9, 2012
• First Posted: January 13, 2012
• Study Start: January 1, 2012
• Primary Completion: December 23, 2021
• Study Completion: December 23, 2021
• Last Updated: January 12, 2022

Record last verified: 2021-12

Locations

US (1)