Clinical trial NCT00817180: Long-term Study, Comparing Vest Therapy to Positive Expiratory Pressure (PEP) Therapy in the Treatment of Cystic Fibrosis
Official title: Multi-centre, Long-term Comparative Trial of High Frequency Chest Wall Oscillation Versus Positive Expiratory Pressure Mask in the Treatment of Cystic Fibrosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cystic Fibrosis
Keywords: physiotherapy
airway clearance techniques
Positive Expiratory Pressure Technique
high frequency Chest Wall Oscillation
vest
Lead sponsor: University of British Columbia
Sponsor class: OTHER
Collaborators: name: Canadian Cystic Fibrosis Foundation
First posted: 2009-01-06
Enrollment: 107
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Difference in the number of respiratory exacerbations during the 1 year study period
timeFrame: 1 year
Secondary outcomes:
measure: The time to the first respiratory exacerbation. Change in FEV1 measured as difference in the yearly mean rate of decline. Cost analysis between the two groups. Quality of life questionnaire. Patient satisfaction questionnaire and Adherence to treatment.
timeFrame: 1 year
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Foothills Medical Centre
state: Alberta
city: Edmonton
country: Canada
facility: Alberta Children's Hospital
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta Hospitals
state: Alberta
city: Vancouver
country: Canada
facility: BC Children's Hospital
state: British Columbia
city: Vancouver
country: Canada
facility: St. Paul's Hospital
state: British Columbia
city: Winnipeg
country: Canada
facility: Children's Hospital of Winnipeg
state: Manitoba
city: St. John's
country: Canada
facility: St. Clare's Mercy Hospital
state: Newfoundland and Labrador
city: Ottawa
country: Canada
facility: Children's Hospital of Eastern Ontario
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa General Hospital
state: Ontario
city: Toronto
country: Canada
facility: The Hospital for Sick Children, Toronto
state: Ontario
city: Montreal
country: Canada
facility: Montreal Children's Hospital
state: Quebec
city: Montreal
country: Canada
facility: CHU Ste-Justine
state: Quebec
city: Quebec
country: Canada
facility: Centre Mere-Enfant du CHUQ
Study officials:
affiliation: BC Children's Hospital, Vancouver
name: Maggie McIlwaine, Physio
role: PRINCIPAL_INVESTIGATOR
affiliation: BC Children's Hospital, Vancouver
name: George Davidson, MD
role: STUDY_DIRECTOR
affiliation: Alberta Children's Hospital
name: Candice Bjornson, MD
role: STUDY_DIRECTOR
affiliation: Alberta Children's Hospital
name: Clare Smith, Physio
role: STUDY_DIRECTOR
affiliation: Children's Hospital of Winnipeg
name: Hans Pasterkamp, MD
role: STUDY_DIRECTOR
affiliation: Children's Hospital of Winnipeg
name: Linda Kraemer, Physio
role: STUDY_DIRECTOR
affiliation: The Hospital for Sick Children, Toronto
name: Felix Ratjen, MD
role: STUDY_DIRECTOR
affiliation: The Hospital for Sick Children, Toronto
name: Jennifer Agnew, Physio
role: STUDY_DIRECTOR
affiliation: Montreal Children's Hospital of the MUHC
name: Larry Lands, MD
role: STUDY_DIRECTOR
affiliation: Montreal Children's Hospital of the MUHC
name: Nancy Alarie, Physio
role: STUDY_DIRECTOR
affiliation: St. Paul's Hospital, Vancouver
name: Pearce Wilcox, MD
role: STUDY_DIRECTOR
affiliation: St. Paul's Hospital, Vancouver
name: Brigette Wilkins, Physio
role: STUDY_DIRECTOR
affiliation: Children's Hospital of Eastern Ontario, Ottawa
name: Sherri Katz, MD
role: STUDY_DIRECTOR
affiliation: Children's Hospital of Eastern Ontario
name: Linda Lapointe, Physio
role: STUDY_DIRECTOR
affiliation: The Ottawa Hospital
name: Shawn Aaron, MD
role: STUDY_DIRECTOR
affiliation: The Ottawa Hospital
name: Lynne Orser, Physio
role: STUDY_DIRECTOR
affiliation: Foothills Medical Centre, Calgary
name: Harvey Rabin, MD
role: STUDY_DIRECTOR
affiliation: Foothills Medical Centre, Calgary
name: Julie Wilson, Physio
role: STUDY_DIRECTOR
affiliation: Janeway Children's Health & Rebab. Centre, St. John's
name: Mary Noseworthy, MD
role: STUDY_DIRECTOR
affiliation: St. Clare's Mercy Hospital, St. John's
name: Stephanie Spencer, Physio
role: STUDY_DIRECTOR
affiliation: University of Alberta Hospitals, Edmonton
name: Peter Zuberbuhler, MD
role: STUDY_DIRECTOR
affiliation: University of Alberta Hospitals, Edmonton
name: Suzanne Bergsten, Physio
role: STUDY_DIRECTOR
affiliation: University of Alberta Hospitals, Edmonton
name: Neil Brown, MD
role: STUDY_DIRECTOR
affiliation: University of Alberta Hospitals, Edmonton
name: Joyce Sharum, Physio
role: STUDY_DIRECTOR
affiliation: CHU Ste-Justine, Montreal
name: Jacques-Edouard Marcotte, MD
role: STUDY_DIRECTOR
affiliation: CHU Ste-Justine, Montreal
name: Nadia Marquis, Physio
role: STUDY_DIRECTOR
affiliation: CHUQ, Universite Laval, Quebec
name: Patrick Daigneault, MD
role: STUDY_DIRECTOR
affiliation: CHUL, Universite Laval, Quebec
name: Christine Bouchard, Physio
role: STUDY_DIRECTOR
References:
citation: McIlwaine MP, Alarie N, Davidson GF, Lands LC, Ratjen F, Milner R, Owen B, Agnew JL. Long-term multicentre randomised controlled study of high frequency chest wall oscillation versus positive expiratory pressure mask in cystic fibrosis. Thorax. 2013 Aug;68(8):746-51. doi: 10.1136/thoraxjnl-2012-202915. Epub 2013 Feb 13.