Treatment of Aspergillus Fumigatus (a Fungal Infection) in Patients With Cystic Fibrosis

Treatment of Aspergillus Fumigatus in Patients With Cystic Fibrosis: A Randomized, Double-blind, Placebo-Controlled Trial

This clinical trial will attempt to determine whether we can improve clinical outcomes for patients with cystic fibrosis who are infected with a fungus called Aspergillus fumigatus.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: Itraconazole

Detailed Description

The aim of this study is to determine whether antibiotic treatment directed against Aspergillus Fumigatus will be effective at preventing respiratory exacerbations and improving pulmonary function in patients with cystic fibrosis(CF) who are chronically colonized/infected with aspergillus. This aim will be accompanied by means of a randomized, double-blind, placebo-controlled clinical trial incorporating two parallel treatment arms.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • Shawn Aaron, The Ottawa Hospital-General Campus
    • Toronto, Ontario, Canada, M5G 1X8
      • Felix Ratjen, The Hospital for Sick Children

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

• Diagnosis of CF as defined by two or more clinical features of CF and a documented sweat chloride greater than 60 mEq/L by quantitative pilocarpine iontophoresis test or a genotype showing two well characterized disease causing mutations
• Patient must be known to be chronically colonized with Aspergillus fumigatus.
• Patients must be clinically stable at randomization, no use of new inhaled, oral or intravenous antibiotics or oral or intravenous corticosteroids during the 14-day period prior to randomization.
• 6 years of age and older
• Patients must weigh at least 20 kg
• Post-menarche females must be using an effective form of contraception.

Exclusion Criteria

• Inability to give informed consent.
• Respiratory culture positive for B.cepacia complex
• Renal function abnormalities-Creatinine greater than 1.5 times upper limit of normal within a 30 day period prior to randomization
• Liver function abnormalities : AST or ALT greater or equal to 2.5 times the upper limit of normal within a 30 day period prior to randomization
• Neutropenia, absolute neutrophil count< or = 1000 within a 3-day period prior to randomization
• History of biliary cirrhosis documented by liver biopsy or imaging.
• History of portal hypertension.
• Investigational drug use within 30 days of randomization date.
• History of alcohol, illicit drug or medication abuse within 1 year of randomization.
• Women who are pregnant, breastfeeding or trying to conceive

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Itraconazole; Itraconazole 5mg/kg/day for 24 weeks	Drug: Itraconazole; Oral Itraconazole 5mg/kg/day or identical placebo for 24 weeks; Other Names: non applicable
Placebo Comparator: Placebo; Placebo/day for 24 weeks	Drug: Itraconazole; Oral Itraconazole 5mg/kg/day or identical placebo for 24 weeks; Other Names: non applicable

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Primary Outcome Measure Will be the Number of Patients Who Experience a Respiratory Exacerbation Requiring Intravenous Antibiotics in the Two Treatment Groups Over the 24 Week Trial Treatment Period.	The Primary outcome measure will be the number of patients who experience a respiratory exacerbation requiring intravenous antibiotics in the two treatment groups over the 24 week trial treatment period.	24 weeks

Collaborators and Investigators

• Sponsor: Ottawa Hospital Research Institute
• Collaborators: The Hospital for Sick Children; The Physicians' Services Incorporated Foundation; Canadian Cystic Fibrosis Foundation
• Investigators: Principal Investigator: Shawn Aaron, MD, OHRI

Publications and helpful links

General Publications

• Aaron SD, Vandemheen KL, Freitag A, Pedder L, Cameron W, Lavoie A, Paterson N, Wilcox P, Rabin H, Tullis E, Morrison N, Ratjen F. Treatment of Aspergillus fumigatus in patients with cystic fibrosis: a randomized, placebo-controlled pilot study. PLoS One. 2012;7(4):e36077. doi: 10.1371/journal.pone.0036077. Epub 2012 Apr 30.

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): August 1, 2010
• Study Completion (Actual): May 1, 2011

Study Registration Dates

• First Submitted: September 10, 2007
• First Submitted That Met QC Criteria: September 11, 2007
• First Posted (Estimate): September 12, 2007

Study Record Updates

• Last Update Posted (Actual): May 10, 2017
• Last Update Submitted That Met QC Criteria: April 3, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: Cystic Fibrosis; randomized controlled clinical trials; Aspergillus Fumigatus
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Itraconazole
• Other Study ID Numbers: 2006768

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO