Long-term Study, Comparing Vest Therapy to Positive Expiratory Pressure (PEP) Therapy in the Treatment of Cystic Fibrosis

Multi-centre, Long-term Comparative Trial of High Frequency Chest Wall Oscillation Versus Positive Expiratory Pressure Mask in the Treatment of Cystic Fibrosis

This study is a preliminary study designed to determine the safety and effectiveness of HFCWO using the InCourage vest system as an airway clearance technique for the treatment of CF. The study will compare HFCWO to the most commonly used airway clearance technique in Canada, namely the Positive Expiratory Pressure technique in patients with CF over a period of one year. As this is a preliminary study, it will not be able to determine if the vest is equivelant to PEP, but will provide the information needed to plan a larger study to answer that question.

Objective This is a pilot study to evaluate the long-term clinical efficacy of high frequency chest wall oscillation (HFCWO) using the inCourage vest system, compared to positive expiratory pressure mask (PEP) in the treatment of patients with cystic fibrosis.

Study Design This is a one year prospective multi-centre randomized controlled trial of HFCWO versus PEP as airway clearance techniques in patients with cystic fibrosis. Number of respiratory exacerbations will be compared between the two treatment arms. Slope of percent predicted in FEV1, activity level, quality of life, cost analysis and subject satisfaction will also be compared.

Number of subjects Enrollment will be completed after 170 subjects have been recruited, approximately 85 in each arm.

Number of sites The study will involve between 14 CF centres in Canada.

PERSCRIBED AIRWAY CLEARANCE TECHNIQUE The test airway clearance technique is the

• High Frequency Chest Wall Oscillation using the InCourage Vest System. This will be compared to
• The Positive Expiratory Pressure Mask Technique. Subjects will be randomized to perform one of these techniques as their airway clearance technique for the period of the study.

PRIMARY ENDPOINT Primary: Difference in the number of respiratory exacerbations. (For definition see Appendix A). Defined by the presence of one major criteria or 2 minor signs or symptoms.

Major Criteria:

• Decrease in FEV1 of ≥10% from best baseline within past 6 months, unresponsive to ventolin.
• Oxygen saturation <90% on room air or ≥ 5% decline from previous baseline.
• New finding(s) on chest radiograph.
• Hemoptysis (more than streaks on more than one occasion in past week).

Minor Signs/symptoms:

• Increased work of breathing or respiratory rate.
• New or increased adventitial sounds on lung exam.
• Weight loss ≥ 5% of body weight or decrease across one major percentile in weight percentile for age within the past 6 months.
• Increased cough.
• Decreased exercise tolerance or level of activity.
• Increased chest congestion or change in sputum.

For minor signs/symptoms, duration of symptoms need to be ≥ 5 days or significant symptom severity.

SECONDARY ENDPOINTS

Secondary:

• The time to the first respiratory exacerbation will be measured in each group using the same definition of a respiratory exacerbation as used for the primary outcome.
• Change in FEV1 measured as difference in the yearly mean rate of decline (Appendix E).
• Cost analysis between the two groups.
• Quality of life questionnaire.
• Patient satisfaction questionnaire.
• Adherence to treatment.

DATA SAFETY MONITORING COMMITTEE

The study will be monitored by a Data Safety Monitoring committee (DSMC). The will communicate regularly either by teleconference, email or by face to face meetings, to deal with issues that arise. The will review all serious adverse events as they occur. The DSMC may request an analysis at any time. At the end of the randomized trial, a report of select final analyses will be provided the DSMC. The study may be terminated if the investigators, medical monitor, or DSMC have significant concerns about the safety of HFCWO based on serious adverse events, other safety data or the conduct of the trial.

STATISTICS Primary Analysis: The number of exacerbations during treatment will be determined in each arm and the difference between the groups calculated with 95% confidence limits as a measure of precision.

Inclusion Criteria:

• Male or female 6 years of age or older at enrollment and be competent in performing spirometry.
• Confirmed diagnosis of CF.
• FEV1> 45% predicted as calculated by Wang reference equations
• Written informed consent (and assent when applicable) obtained from subject or subject's legal representative and ability for subject to comply with the requirements of the study.
• Clinically stable at enrollment with no evidence of respiratory exacerbation within a month of enrollment as assessed by the site CF Physician.
• Willingness to adhere to prescribed treatment regimen.

Exclusion Criteria:

• Diagnosis of Allergic Broncho-Pulmonary Aspergillosis, or a persistent culture for B.cepacia complex within the previous 1 year period
• .On active treatment for non Tuberculous Mycobacterium.
• Use of intravenous antibiotics within the previous 14 days of enrollment.
• Initiation and or change in maintenance therapy within 14 days of enrollment.
• Use of systemic corticosteriods (1mg/kg if < 20 kg or 20 mg of prednisone per day) within 14 days of enrollment.
• Concurrent participation in another study that could potentially affect the present study.
• Haemoptysis of over 20 mls on more than 2 occasions within the previous 30 days from enrollment.
• A pneumothorax in the six months preceding the study.
• Presence of a condition or abnormality that in the opinion of the site CF Physician would compromise the safety of the patient or the quality of the data.