- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00557089
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
Study Overview
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.
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
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Ontario
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Toronto, Ontario, Canada, M5G 1X8
- The Hospital for Sick Children
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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 Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Other: 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.
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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 Names:
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.
|
Other: 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.
|
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 Names:
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.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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)
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The duration of the patient's involvement in the study (approximately 3 months)
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Change in FEV1 % predicted
Time Frame: The duration of the patient's involvement in the study (approximately 3 months)
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The duration of the patient's involvement in the study (approximately 3 months)
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Change in FVC (in litres)
Time Frame: The duration of the patient's involvement in the study (approximately 3 months)
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The duration of the patient's involvement in the study (approximately 3 months)
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Change in FVC % predicted
Time Frame: The duration of the patient's involvement in the study (approximately 3 months)
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The duration of the patient's involvement in the study (approximately 3 months)
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Change in FEF25-75 (liters/sec)
Time Frame: The duration of the patient's involvement in the study (approximately 3 months)
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The duration of the patient's involvement in the study (approximately 3 months)
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Change in FEF25-75 % predicted
Time Frame: The duration of the patient's involvement in the study (approximately 3 months)
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The duration of the patient's involvement in the study (approximately 3 months)
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Change in exhaled nitric oxide concentrations
Time Frame: The duration of the patient's involvement in the study (approximately 3 months)
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The duration of the patient's involvement in the study (approximately 3 months)
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Incidence of adverse events and serious adverse events
Time Frame: Duration of the study (approximately 1 year)
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Duration of the study (approximately 1 year)
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Felix Ratjen, MD, The Hospital for Sick Children, Toronto Canada
Publications and helpful links
General Publications
- 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.
- 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.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 1000010903
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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