A Trial of Pulmozyme Withdrawal on Exercise Tolerance in Cystic Fibrosis Subjects With Severe Lung Disease (TOPIC)

Study Overview
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Brief Summary
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This was a multicenter, randomized, double-blind, placebo-controlled study of patients with severe, though stable, cystic fibrosis (CF) whose routine treatment included Pulmozyme. Patients were randomized to either continue Pulmozyme or have therapy withdrawn for 2 weeks (placebo group). Patients must have had stable CF symptoms without any change in therapy for 2 weeks prior to enrollment in order to participate.

Official Title
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A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Pulmozyme Withdrawal on Exercise Tolerance in Cystic Fibrosis Subjects With Severe Lung Disease

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: Dornase alfa
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed Informed Consent Form and, if applicable, Assent Form Age ≥ 14 years old at screening Proven diagnosis of CF Ability to perform acceptable and reproducible spirometry maneuvers at screening FVC ≤ 45% predicted for race, height, age, and sex at screening Chronic use of Pulmozyme for at least 3 months in the last year and daily or twice daily use during the 14 days prior to screening Stable regimen of chest physiotherapy (CPT) for at least 14 days prior to screening Ability to complete the 6-minute walk test at screening Ability to complete the 6-minute walk test and spirometry at Visit 2 If on routine tobramycin solution for inhalation (i.e., TOBI®) or other cycled antibiotic therapy, intention to either start or stop therapy at the time of Visit 2 (based on routine therapy cycle; no other planned change in this antibiotic regimen for 28 days before or 28 days after Visit 2) Clinically stable with no change in medications during the 14 days prior to screening Exclusion Criteria: Use of an investigational drug or device within 28 days prior to screening Previous episode of acute respiratory failure requiring assisted ventilation within 2 years prior to screening Previous lung transplant Any cardiac disease that would contraindicate performing the 6-minute walk test Pregnancy or nursing Known hypersensitivity or other contraindication to the use of Pulmozyme Previous completion or premature discontinuation of study drug or withdrawal from this study More than one prior screening failure for this study at any time or any prior screening failure for this study within the last 28 days

Ages Eligible for Study
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Minimum Age: 14 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: placebo<br>* 2.5 mg inhalation dose twice daily for 14±2 days<br>|
| Experimental: Dornase alfa<br> | Drug: Dornase alfa<br>* 2.5 mg inhalation dose twice daily for 14±2 days<br>* Other names: Pulmozyme;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Distance Walked in the 6-minute Walk Test | Change in distance walked was defined as (distance walked in 6 minutes at baseline [Day 0]) - (distance walked in 6 minutes at Day 14) in meters. | From baseline to Day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Pulmonary Function as Measured by FEV1 and FVC | FEV1 (forced expiratory volume in 1 second) and FVC (forced vital capacity) were recorded at Day 0 (baseline) and Day 14. Change in FEV1 and FVC from baseline to Day 14 was reported as a percentage of values predicted for age, height, and race. | From baseline to Day 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lung disease, CF, Pulmozyme