Trial Outcomes & Findings for Early Intervention in Cystic Fibrosis Exacerbation (NCT NCT01104402)

Results Overview

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

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

267 participants

Primary outcome timeframe

12 months

Results posted on

2017-10-23

Participant Flow

Participant milestones

Participant milestones
Measure	Standard Care Subjects will receive education about signs and symptoms indicative of worsening CF.	Home Monitoring Subjects will be randomized to monitor home spirometry and symptoms using a handheld device. Home lung function and symptom monitoring: subjects in the intervention arm will measure spirometry and CF symptoms with the use of a handheld device.
Overall Study STARTED	132	135
Overall Study COMPLETED	111	102
Overall Study NOT COMPLETED	21	33

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Early Intervention in Cystic Fibrosis Exacerbation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Standard Care n=132 Participants Subjects will receive education about signs and symptoms indicative of worsening CF.	Home Monitoring n=135 Participants Subjects will be randomized to monitor home spirometry and symptoms using a handheld device. Home lung function and symptom monitoring: subjects in the intervention arm will measure spirometry and CF symptoms with the use of a handheld device.	Total n=267 Participants Total of all reporting groups
Age, Categorical <=18 years	39 Participants n=5 Participants	38 Participants n=7 Participants	77 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	93 Participants n=5 Participants	97 Participants n=7 Participants	190 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	27.8 years STANDARD_DEVIATION 12.5 • n=5 Participants	26.5 years STANDARD_DEVIATION 11.5 • n=7 Participants	27.1 years STANDARD_DEVIATION 12.0 • n=5 Participants
Sex: Female, Male Female	68 Participants n=5 Participants	68 Participants n=7 Participants	136 Participants n=5 Participants
Sex: Female, Male Male	64 Participants n=5 Participants	67 Participants n=7 Participants	131 Participants n=5 Participants
Region of Enrollment United States	132 Participants n=5 Participants	135 Participants n=7 Participants	267 Participants n=5 Participants

PRIMARY outcome

Timeframe: 12 months

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

Outcome measures

Outcome measures
Measure	Standard Care n=132 Participants Subjects will receive education about signs and symptoms indicative of worsening CF.	Home Monitoring n=135 Participants Subjects will be randomized to monitor home spirometry and symptoms using a handheld device. Home lung function and symptom monitoring: subjects in the intervention arm will measure spirometry and CF symptoms with the use of a handheld device.
Change in FEV1	-0.07 Liters Interval -0.13 to -0.02	-0.08 Liters Interval -0.13 to -0.03

SECONDARY outcome

Timeframe: 12 months

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.

Outcome measures

Outcome measures
Measure	Standard Care n=132 Participants Subjects will receive education about signs and symptoms indicative of worsening CF.	Home Monitoring n=135 Participants Subjects will be randomized to monitor home spirometry and symptoms using a handheld device. Home lung function and symptom monitoring: subjects in the intervention arm will measure spirometry and CF symptoms with the use of a handheld device.
Cystic Fibrosis Respiratory Symptom Diary (CFRSD)	4.56 units on a scale Standard Deviation 12.8	0.45 units on a scale Standard Deviation 13.6

SECONDARY outcome

Timeframe: 12 months

Percentage of participants who experienced at least one acute pulmonary exacerbation

Outcome measures

Outcome measures
Measure	Standard Care n=132 Participants Subjects will receive education about signs and symptoms indicative of worsening CF.	Home Monitoring n=135 Participants Subjects will be randomized to monitor home spirometry and symptoms using a handheld device. Home lung function and symptom monitoring: subjects in the intervention arm will measure spirometry and CF symptoms with the use of a handheld device.
Pulmonary Exacerbations	70 percentage of participants	75 percentage of participants

SECONDARY outcome

Timeframe: Change from baseline to 12 months

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.

Outcome measures

Outcome measures
Measure	Standard Care n=132 Participants Subjects will receive education about signs and symptoms indicative of worsening CF.	Home Monitoring n=135 Participants Subjects will be randomized to monitor home spirometry and symptoms using a handheld device. Home lung function and symptom monitoring: subjects in the intervention arm will measure spirometry and CF symptoms with the use of a handheld device.
Change in Health Related Quality of Life Scores as Assessed by the Cystic Fibrosis Questionnaire Revised (CFQ-R) (Respiratory Subscale Only(	-3.07 units on a scale Standard Deviation 15.5	-.44 units on a scale Standard Deviation 16.67

SECONDARY outcome

Timeframe: Change from baseline to 12 months

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.

Outcome measures

Outcome measures
Measure	Standard Care n=111 Participants Subjects will receive education about signs and symptoms indicative of worsening CF.	Home Monitoring n=102 Participants Subjects will be randomized to monitor home spirometry and symptoms using a handheld device. Home lung function and symptom monitoring: subjects in the intervention arm will measure spirometry and CF symptoms with the use of a handheld device.
Treatment Burden	0.6 units on a scale Standard Deviation 1.4	2.9 units on a scale Standard Deviation 2.6

SECONDARY outcome

Timeframe: 12 months

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.

Outcome measures

Outcome measures
Measure	Standard Care n=132 Participants Subjects will receive education about signs and symptoms indicative of worsening CF.	Home Monitoring n=135 Participants Subjects will be randomized to monitor home spirometry and symptoms using a handheld device. Home lung function and symptom monitoring: subjects in the intervention arm will measure spirometry and CF symptoms with the use of a handheld device.
Change in Prevalence of Resistant Species of Bacteria	3 percentage of subjects with new MRPA	8 percentage of subjects with new MRPA

SECONDARY outcome

Timeframe: 12 months

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.

Outcome measures

Outcome measures
Measure	Standard Care n=132 Participants Subjects will receive education about signs and symptoms indicative of worsening CF.	Home Monitoring n=135 Participants Subjects will be randomized to monitor home spirometry and symptoms using a handheld device. Home lung function and symptom monitoring: subjects in the intervention arm will measure spirometry and CF symptoms with the use of a handheld device.
Serious Adverse Events (SAE)	0.023 proportion of participants with SAEs	0.030 proportion of participants with SAEs

Adverse Events

Standard Care

Serious events: 3 serious events

Other events: 47 other events

Deaths: 0 deaths

Home Monitoring

Serious events: 4 serious events

Other events: 53 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Standard Care n=132 participants at risk Subjects will receive education about signs and symptoms indicative of worsening CF.	Home Monitoring n=135 participants at risk Subjects will be randomized to monitor home spirometry and symptoms using a handheld device. Home lung function and symptom monitoring: subjects in the intervention arm will measure spirometry and CF symptoms with the use of a handheld device.
Respiratory, thoracic and mediastinal disorders Exacerbation of Cystic Fibrosis	2.3% 3/132 • Number of events 3 • 12 months	3.0% 4/135 • Number of events 4 • 12 months

Other adverse events

Other adverse events
Measure	Standard Care n=132 participants at risk Subjects will receive education about signs and symptoms indicative of worsening CF.	Home Monitoring n=135 participants at risk Subjects will be randomized to monitor home spirometry and symptoms using a handheld device. Home lung function and symptom monitoring: subjects in the intervention arm will measure spirometry and CF symptoms with the use of a handheld device.
Gastrointestinal disorders nausea	7.6% 10/132 • Number of events 10 • 12 months	11.9% 16/135 • Number of events 17 • 12 months
Respiratory, thoracic and mediastinal disorders sputum increased	28.0% 37/132 • Number of events 153 • 12 months	27.4% 37/135 • Number of events 187 • 12 months

Additional Information

Dr. Noah Lechtzin & Dr. Christopher Goss

Johns Hopkins University & University of Washington

Phone: 410-502-7044

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place