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

November 9, 2007
August 30, 2013
January 2008
June 2009   (final data collection date for primary outcome measure)
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 ]
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) ]
Complete list of historical versions of study NCT00557089 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Change in FEV1 % predicted [ Time Frame: The duration of the patient's involvement in the study (approximately 3 months) ]
  • Change in FVC (in litres) [ Time Frame: The duration of the patient's involvement in the study (approximately 3 months) ]
  • Change in FVC % predicted [ Time Frame: The duration of the patient's involvement in the study (approximately 3 months) ]
  • Change in FEF25-75 (liters/sec) [ Time Frame: The duration of the patient's involvement in the study (approximately 3 months) ]
  • Change in FEF25-75 % predicted [ Time Frame: The duration of the patient's involvement in the study (approximately 3 months) ]
  • Change in exhaled nitric oxide concentrations [ Time Frame: The duration of the patient's involvement in the study (approximately 3 months) ]
  • Incidence of adverse events and serious adverse events [ Time Frame: Duration of the study (approximately 1 year) ]
Not Provided
Not Provided
 
The Effect of rhDNase on Ventilation Inhomogeneity in Patients With Cystic Fibrosis
Randomized, Placebo-controlled Trial on the Effect of rhDNase on Ventilation Inhomogeneity in Patients With Cystic Fibrosis

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

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.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Cystic Fibrosis
  • 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.
  • 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.
    Interventions:
    • Drug: rhDNAse
    • Other: Placebo
  • 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.
    Interventions:
    • Drug: rhDNAse
    • Other: Placebo
Amin R, Subbarao P, Lou W, Jabar A, Balkovec S, Jensen R, Kerrigan S, Gustafsson P, Ratjen F. The effect of dornase alfa on ventilation inhomogeneity in patients with cystic fibrosis. Eur Respir J. 2010 Aug 6; [Epub ahead of print]

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
17
June 2009
June 2009   (final data collection date for primary outcome measure)

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
Both
6 Years to 18 Years
No
Contact information is only displayed when the study is recruiting subjects
Canada
 
NCT00557089
1000010903
No
Felix Ratjen, The Hospital for Sick Children
The Hospital for Sick Children
Not Provided
Principal Investigator: Felix Ratjen, MD The Hospital for Sick Children, Toronto Canada
The Hospital for Sick Children
August 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP