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

NCT ID: NCT00557089

Last Updated: 2013-09-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-01-31
• Study Completion Date: 2009-06-30

Brief Summary

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

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.

Conditions

Cystic Fibrosis

Keywords

Pediatrics; Cystic Fibrosis; Lung Clearance Index; rhDNAse

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: OTHER

rhDNAse

Intervention Type: DRUG

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.

Placebo

Intervention Type: OTHER

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.

Group Type: OTHER

rhDNAse

Intervention Type: DRUG

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.

Placebo

Intervention Type: OTHER

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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: OTHER

Other Intervention Names

Brand Name: Pulmozyme

Eligibility 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

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Hospital for Sick Children

OTHER

Sponsor Role: lead

Responsible Party

Felix Ratjen

Division Head, Respiratory Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Felix Ratjen, MD

Role: PRINCIPAL_INVESTIGATOR

The Hospital for Sick Children, Toronto Canada

Locations

The Hospital for Sick Children

Toronto, Ontario, Canada

Countries

Canada

References

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. Epub 2010 Aug 6.

Reference Type: RESULT

PMID: 20693248 (View on PubMed)

Yang C, Montgomery M. Dornase alfa for cystic fibrosis. Cochrane Database Syst Rev. 2021 Mar 18;3(3):CD001127. doi: 10.1002/14651858.CD001127.pub5.

Reference Type: DERIVED

PMID: 33735508 (View on PubMed)

Other Identifiers

1000010903

Identifier Type: -

Identifier Source: org_study_id