Early Intervention in Cystic Fibrosis Exacerbation

Study Overview
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Brief Summary
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Individuals with cystic fibrosis (CF) develop chronic lung infections and suffer intermittent acute exacerbations of their lung disease. Most exacerbations are not treated until they cause increased symptoms, and patients seek medical attention. This proposal details a study of home lung function and symptom monitoring. Subjects will be randomly assigned to one of two groups: 1) home monitoring, in which spirometry and symptoms are recorded; or 2) standard care. The home monitoring data will be transmitted electronically to the study center. If spirometry or symptoms have deteriorated substantially, treatment for a CF pulmonary exacerbation will be initiated. It is anticipated that use of home monitoring will lead to earlier, more reliable recognition and treatment of exacerbations, which will translate into better lung health.

Detailed Description
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Individuals with CF develop chronic lung infections and suffer intermittent exacerbations, which require intensive treatment with antibiotics. The most common and useful objective measure of CF lung disease is spirometry. Chronic treatment of CF lung disease requires airway clearance, mucolytics and antibiotics. These treatments have been quite successful and there is evidence that early, aggressive treatment of lung disease results in better outcomes. Unfortunately, most exacerbations are not treated until they cause pronounced deterioration in symptoms, which prompts patients to seek medical attention. Self-monitoring of clinical status has improved outcomes in many other disorders such as asthma, diabetes mellitus, and lung transplantation. This is an important, randomized trial of home lung function and symptom monitoring in CF. Subjects will be assigned to one of two groups: 1) Home monitoring, in which spirometry and symptoms are recorded daily; or 2) Standard Care. The home monitoring data will be transmitted electronically twice weekly to the study center, where the results will be reviewed. If spirometry or symptoms have deteriorated substantially below baseline, treatment for a CF pulmonary exacerbation will be initiated. It is anticipated that use of home monitoring will translate into better clinical outcomes. We will test the hypothesis that if pulmonary exacerbations are identified and treated earlier than the current standard of care, the progression of lung disease will be slowed.

Official Title
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Early Intervention in Cystic Fibrosis Exacerbation

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Device: Home lung function and symptom monitoring


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: CF diagnosis confirmed with sweat test, abnormal nasal potential difference and/or genetic testing Age 14 and older Able to perform spirometry Clinically stable without antibiotic treatment for a pulmonary exacerbation in the two weeks prior to the screening visit Forced expiratory volume in the first second (FEV1) greater than 25% of predicted at screening Exclusion Criteria: History of solid organ transplant Participation in any interventional trial within the last 30 days Inability to speak and read the English language well enough to complete questionnaires Colonization with Burkholderia cepacia genomovar III within the last 24 months Currently receiving antimicrobial treatment specifically used to treat active non-tuberculosis mycobacterium Confirmed diagnosis of allergic bronchopulmonary aspergillosis (ABPA) as defined by the Cystic Fibrosis Foundation (CFF) guidance document that is being actively treated

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Standard Care<br>Subjects will receive education about signs and symptoms indicative of worsening CF. | |
| Active Comparator: Home monitoring<br>Subjects will be randomized to monitor home spirometry and symptoms using a handheld device. | Device: Home lung function and symptom monitoring<br>* subjects in the intervention arm will measure spirometry and CF symptoms with the use of a handheld device.<br>* Other names: Jaeger AM2 monitor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in FEV1 | The primary outcome variable is FEV1 which will be obtained at quarterly study visits. The primary analysis will use a linear mixed effects model incorporating all FEV1 measurements to estimate the 52-week change in FEV1 | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cystic Fibrosis Respiratory Symptom Diary (CFRSD) | Change in CF respiratory symptoms as measured by the CFRSD. The CFRSD consists of 8 items which quantify symptom severity for the previous 24 hours to capture the magnitude of symptoms in stable CF, during medically treated CF exacerbations, and during recovery from an exacerbation. The CFRSD also includes emotional and activity impacts. Emotional impacts include frustration, sadness/depression, irritability, worry, and difficulty sleeping. Activity impacts include time spent sitting or lying down, reduction of usual activities, and missing school or work. will be analyzed using a linear mixed effects model incorporating baseline randomization factors FEV1 (<50%, 50-75%, and >75% predicted) and age (14-18 & 19+), treatment group, time (in weeks) and the interaction between treatment and time. The range of scores is 8 to 40 with higher scores indicating more severe symptoms. | 12 months | 
| Pulmonary Exacerbations | Percentage of participants who experienced at least one acute pulmonary exacerbation | 12 months | 
| Change in Health Related Quality of Life Scores as Assessed by the Cystic Fibrosis Questionnaire Revised (CFQ-R) (Respiratory Subscale Only( | Change in health related quality of life as measured by the Cystic Fibrosis Questionnaire revised (CFQ-R)will be analyzed using a linear mixed effects model incorporating baseline randomization factors FEV1 (<50%, 50-75%, and >75% predicted) and age (14-18 & 19+), treatment group, time (in weeks) and the interaction between treatment and time. The CFQ-R measures functioning in a variety of domains, including Physical Functioning, Vitality, Health Perceptions, Respiratory Symptoms, Treatment Burden, Role Functioning, Emotional Functioning, and Social Functioning. Only the respiratory subscale of the the CFQ-R was evaluated. This ranges from 0 to 100 with higher scores indicating better respiratory quality of life. A negative number indicates a decrease in respiratory quality of life. | Change from baseline to 12 months | 
| Treatment Burden | Change in treatment burden as measured by the Cystic Fibrosis Questionnaire revised (CFQ-R)will be analyzed using a linear mixed effects model incorporating baseline randomization factors FEV1 (<50%, 50-75%, and >75% predicted) and age (14-18 & 19+), treatment group, time (in weeks) and the interaction between treatment and time. Scores range from 0-100 with higher scores indicating less treatment burden. | Change from baseline to 12 months | 
| Change in Prevalence of Resistant Species of Bacteria | Change in prevalence of resistant species of bacteria (Methicillin Resistant S. aureus, Pseudomonas aeruginosa, Burkolderia cepacia, Stenotrophomona maltophilia, Achromobacterxylosoxidans) in sputum between baseline and final visit (Visit 5 or early withdrawal) will be summarized by treatment group. | 12 months | 
| Serious Adverse Events (SAE) | Adverse event rates will be coded by body system and MedDRA classification term. Adverse events will be tabulated by treatment group and will include the number of subjects for whom the event occurred, the rate of occurrence, and the severity and relationship to study participation or study procedures. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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telemedicine, spirometer, CF, pulmonary, home monitoring