The Effect of rhDNase on Ventilation Inhomogeneity in Patients With Cystic Fibrosis
Information source: The Hospital for Sick Children
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Cystic Fibrosis
Intervention: rhDNAse (Drug); Placebo (Other)
Phase: Phase 4
Status: Completed
Sponsored by: The Hospital for Sick Children Official(s) and/or principal investigator(s): Felix Ratjen, MD, Principal Investigator, Affiliation: The Hospital for Sick Children, Toronto Canada
Summary
This study will assess whether rhDNase treatment improves ventilation inhomogeneity as
assessed by lung clearance index (LCI) in patients with cystic fibrosis (CF).
Clinical Details
Official title: Randomized, Placebo-controlled Trial on the Effect of rhDNase on Ventilation Inhomogeneity in Patients With Cystic Fibrosis
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: The change in LCI from baseline to end of treatment in rhDnase treated patients versus patients receiving placebo
Secondary outcome: Change in FEV1 % predictedChange in FVC (in litres) Change in FVC % predicted Change in FEF25-75 (liters/sec) Change in FEF25-75 % predicted Change in exhaled nitric oxide concentrations Incidence of adverse events and serious adverse events
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
Minimum age: 6 Years.
Maximum age: 18 Years.
Gender(s): Both.
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
Locations and Contacts
The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada
Additional Information
Starting date: January 2008
Last updated: August 30, 2013
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