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

Cystic Fibrosis Clinical Trial

Official title:

Randomized, Placebo-controlled Trial on the Effect of rhDNase on Ventilation Inhomogeneity in Patients With Cystic Fibrosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00557089
• Other study ID #: 1000010903
• Status: Completed
• Phase: Phase 4
• First received: November 9, 2007
• Last updated: August 30, 2013
• Start date: January 2008
• Est. completion date: June 2009

Study information

• Verified date: August 2013
• Source: The Hospital for Sick Children
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Ethics Review Committee
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: June 2009
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Years to 18 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

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:
• 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.

Locations

Country	Name	City	State
Canada	The Hospital for Sick Children	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
The Hospital for Sick Children

Country where clinical trial is conducted

Canada, 

References & Publications (1)

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. 2011 Apr;37(4):806-12. doi: 10.1183/09031936.00072510. Ep — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The change in LCI from baseline to end of treatment in rhDnase treated patients versus patients receiving placebo		The duration of the patient's involvement in the study (approximately 3 months)	No
Secondary	Change in FEV1 % predicted		The duration of the patient's involvement in the study (approximately 3 months)	No
Secondary	Change in FVC (in litres)		The duration of the patient's involvement in the study (approximately 3 months)	No
Secondary	Change in FVC % predicted		The duration of the patient's involvement in the study (approximately 3 months)	No
Secondary	Change in FEF25-75 (liters/sec)		The duration of the patient's involvement in the study (approximately 3 months)	No
Secondary	Change in FEF25-75 % predicted		The duration of the patient's involvement in the study (approximately 3 months)	No
Secondary	Change in exhaled nitric oxide concentrations		The duration of the patient's involvement in the study (approximately 3 months)	No
Secondary	Incidence of adverse events and serious adverse events		Duration of the study (approximately 1 year)	Yes