The Effect of rhDNase on Ventilation Inhomogeneity in Patients With Cystic Fibrosis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Felix Ratjen, The Hospital for Sick Children
ClinicalTrials.gov Identifier:
NCT00557089
First received: November 9, 2007
Last updated: August 30, 2013
Last verified: August 2013
  Purpose

This study will assess whether rhDNase treatment improves ventilation inhomogeneity as assessed by lung clearance index (LCI) in patients with cystic fibrosis (CF).


Condition Intervention Phase
Cystic Fibrosis
Drug: rhDNAse
Other: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized, Placebo-controlled Trial on the Effect of rhDNase on Ventilation Inhomogeneity in Patients With Cystic Fibrosis

Resource links provided by NLM:


Further study details as provided by The Hospital for Sick Children:

Primary Outcome Measures:
  • The change in LCI from baseline to end of treatment in rhDnase treated patients versus patients receiving placebo [ Time Frame: The duration of the patient's involvement in the study (approximately 3 months) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in FEV1 % predicted [ Time Frame: The duration of the patient's involvement in the study (approximately 3 months) ] [ Designated as safety issue: No ]
  • Change in FVC (in litres) [ Time Frame: The duration of the patient's involvement in the study (approximately 3 months) ] [ Designated as safety issue: No ]
  • Change in FVC % predicted [ Time Frame: The duration of the patient's involvement in the study (approximately 3 months) ] [ Designated as safety issue: No ]
  • Change in FEF25-75 (liters/sec) [ Time Frame: The duration of the patient's involvement in the study (approximately 3 months) ] [ Designated as safety issue: No ]
  • Change in FEF25-75 % predicted [ Time Frame: The duration of the patient's involvement in the study (approximately 3 months) ] [ Designated as safety issue: No ]
  • Change in exhaled nitric oxide concentrations [ Time Frame: The duration of the patient's involvement in the study (approximately 3 months) ] [ Designated as safety issue: No ]
  • Incidence of adverse events and serious adverse events [ Time Frame: Duration of the study (approximately 1 year) ] [ Designated as safety issue: Yes ]

Enrollment: 17
Study Start Date: January 2008
Study Completion Date: June 2009
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1
This arm will receive the active treatment for 28 days, followed by a 28 day washout period and then the placebo treatment for 28 days.
Drug: rhDNAse
2.5 mg rhDNase will be dispensed in 2.5 ml vials and administered once a day for 28 days. Treatment will be administered by inhalation.
Other Name: Brand Name: Pulmozyme
Other: Placebo
2.5 mg of the placebo will be dispensed in 2.5 ml vials and administered once a day over 28 days. Treatment will be administered by inhalation.
2
This arm will receive the placebo treatment for 28 days, followed by a 28 day washout period and then the active treatment for 28 days.
Drug: rhDNAse
2.5 mg rhDNase will be dispensed in 2.5 ml vials and administered once a day for 28 days. Treatment will be administered by inhalation.
Other Name: Brand Name: Pulmozyme
Other: Placebo
2.5 mg of the placebo will be dispensed in 2.5 ml vials and administered once a day over 28 days. Treatment will be administered by inhalation.

Detailed Description:

Life expectancy in CF patients has greatly increased due to improved clinical care. While this is certainly beneficial to CF patients, it has made it more difficult to assess the effect of therapeutic interventions. Currently, FEV1 remains the primary outcome parameter for most clinical trials, but many CF patients have normal pulmonary function and the annual rate of decline is now less than 2 %. Therefore, additional parameters are needed that are more sensitive to define abnormalities in CF patients and that can be used in therapeutic trials.

Gas mixing techniques have been shown to be sensitive parameters to define abnormalities in patients with cystic fibrosis, but it is unclear how useful this technique is to detect changes after a therapeutic intervention. Abnormalities in gas clearance from the lung are largely due to retention of inhaled gases due to mucous obstruction in the lower airways and can be assessed with the lung clearance index (LCI). Interventions that improve mucous accumulation are expected to improve lung clearance as assessed by this technique. RhDNase has been demonstrated to improve lung function and reduce pulmonary exacerbations in patients with cystic fibrosis due to improved mucus clearance.

Lung clearance index (LCI) has been shown to be more sensitive than spirometry in detecting abnormalities in CF patients. Clear cut-offs have been found which can differentiate normal patients from even newly diagnosed CF patients. However, little is known about how LCI may change with treatment.

  Eligibility

Ages Eligible for Study:   6 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of CF as defined by clinical features of CF and a documented sweat chloride > 60 mEq/L by quantitative pilocarpine iontophoresis test or a genotype showing two well characterized disease causing mutations
  • Informed consent and verbal assent (as appropriate) has been provided by the subject's parent or legal guardian and the subject
  • 6-18 years of age at enrolment
  • Able to perform reproducible spirometry
  • Clinically stable at enrolment
  • Ability to comply with medication use, study visits and study procedures as judged by the site investigator
  • FEV1 % predicted > 70 % as calculated by the Wang reference equations

Exclusion Criteria:

  • Respiratory culture positive for:

    • NTM within past year or AFB positive at screening (sputum only)
    • B. cepacia complex within past year or at screening
  • Use of intravenous antibiotics or oral quinolones within 14 days of screening
  • Investigational drug use within 30 days of screening
  • History of alcohol, illicit drug or medication abuse within 1 year of screening
  • Other major organ dysfunction excluding pancreatic dysfunction
  • History of lung transplantation or currently on lung transplant list
  • Physical findings at screening that would compromise the safety of the participant or the quality of the study data
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00557089

Locations
Canada, Ontario
The Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
Sponsors and Collaborators
The Hospital for Sick Children
Investigators
Principal Investigator: Felix Ratjen, MD The Hospital for Sick Children, Toronto Canada
  More Information

Publications:
Responsible Party: Felix Ratjen, Division Head, Respiratory Medicine, The Hospital for Sick Children
ClinicalTrials.gov Identifier: NCT00557089     History of Changes
Other Study ID Numbers: 1000010903
Study First Received: November 9, 2007
Last Updated: August 30, 2013
Health Authority: Canada: Ethics Review Committee

Keywords provided by The Hospital for Sick Children:
Pediatrics
Cystic Fibrosis
Lung Clearance Index
rhDNAse

Additional relevant MeSH terms:
Cystic Fibrosis
Fibrosis
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on July 20, 2014