Trial Outcomes & Findings for Effect of Positive Airway Pressure on Reducing Airway Reactivity in Patients With Asthma (CPAP) (NCT NCT01629823)
NCT ID: NCT01629823
Last Updated: 2017-05-15
Results Overview
The primary outcome measure was the change in provocative concentration of methacholine causing a 20% fall in forced expiratory volume in 1 second (FEV₁) (PC20) from baseline to 12 weeks. Modified American Thoracic Society guidelines were followed for pre-bronchodilator spirometry and methacholine challenge testing using the 5 breath dosimeter technique. Up to eleven doses, each a doubling concentration of methacholine (Provocholine™), were inhaled starting at 0.03 mg/mL until a 20% or greater fall in FEV₁ occurred; the maximum dose was 32 mg/mL. Breaths each of doubling concentrations of methacholine were inhaled from a calibrated DeVilbiss™ 646 nebulizer.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
209 participants
Primary outcome timeframe
12 weeks after randomization
Results posted on
2017-05-15
Participant Flow
209 individuals were enrolled in the study. 15 of those participants were excluded from data analysis due to significant data irregularities at one clinical site
Participant milestones
| Measure |
CPAP Less Than 1 cm Water (H₂O)
Continuous Positive Airway Pressure device (Resmed, Swift, Mirage): Participants will be randomized to one of three pre-set CPAP pressures: less than 1 cm water (H₂O), 5 cm H₂O or 10 cm H₂O. They will be instructed to use the CPAP device every night for 12 weeks. Methacholine airways reactivity will be measured at the end of these 12 weeks.
|
CPAP 5cm H₂O
Continuous Positive Airway Pressure device (Resmed, Swift, Mirage): Participants will be randomized to one of three pre-set CPAP pressures: less than 1 cm water (H₂O), 5 cm H₂O or 10 cm H₂O. They will be instructed to use the CPAP device every night for 12 weeks. Methacholine airways reactivity will be measured at the end of these 12 weeks.
|
CPAP 10cm H₂O
Continuous Positive Airway Pressure device (Resmed, Swift, Mirage): Participants will be randomized to one of three pre-set CPAP pressures: less than 1 cm water (H₂O), 5 cm H₂O or 10 cm H₂O. They will be instructed to use the CPAP device every night for 12 weeks. Methacholine airways reactivity will be measured at the end of these 12 weeks.
|
|---|---|---|---|
|
Trial Period
STARTED
|
66
|
69
|
59
|
|
Trial Period
COMPLETED
|
53
|
56
|
49
|
|
Trial Period
NOT COMPLETED
|
13
|
13
|
10
|
|
Washout Period
STARTED
|
54
|
57
|
50
|
|
Washout Period
COMPLETED
|
51
|
51
|
50
|
|
Washout Period
NOT COMPLETED
|
3
|
6
|
0
|
Reasons for withdrawal
| Measure |
CPAP Less Than 1 cm Water (H₂O)
Continuous Positive Airway Pressure device (Resmed, Swift, Mirage): Participants will be randomized to one of three pre-set CPAP pressures: less than 1 cm water (H₂O), 5 cm H₂O or 10 cm H₂O. They will be instructed to use the CPAP device every night for 12 weeks. Methacholine airways reactivity will be measured at the end of these 12 weeks.
|
CPAP 5cm H₂O
Continuous Positive Airway Pressure device (Resmed, Swift, Mirage): Participants will be randomized to one of three pre-set CPAP pressures: less than 1 cm water (H₂O), 5 cm H₂O or 10 cm H₂O. They will be instructed to use the CPAP device every night for 12 weeks. Methacholine airways reactivity will be measured at the end of these 12 weeks.
|
CPAP 10cm H₂O
Continuous Positive Airway Pressure device (Resmed, Swift, Mirage): Participants will be randomized to one of three pre-set CPAP pressures: less than 1 cm water (H₂O), 5 cm H₂O or 10 cm H₂O. They will be instructed to use the CPAP device every night for 12 weeks. Methacholine airways reactivity will be measured at the end of these 12 weeks.
|
|---|---|---|---|
|
Trial Period
Missed visit
|
11
|
9
|
8
|
|
Trial Period
Pre-diluent FEV₁ predicted <70%
|
1
|
1
|
1
|
|
Trial Period
Pregnancy
|
1
|
0
|
0
|
|
Trial Period
Adverse Event
|
0
|
1
|
0
|
|
Trial Period
Out-of-window visit
|
0
|
2
|
0
|
|
Trial Period
Failed to hold medication
|
0
|
0
|
1
|
|
Washout Period
Safety
|
2
|
5
|
0
|
|
Washout Period
Pregnancy
|
1
|
0
|
0
|
|
Washout Period
Protocol Violation
|
0
|
1
|
0
|
Baseline Characteristics
Effect of Positive Airway Pressure on Reducing Airway Reactivity in Patients With Asthma (CPAP)
Baseline characteristics by cohort
| Measure |
CPAP Less Than 1 cm H₂O
n=66 Participants
Continuous Positive Airway Pressure device (Resmed, Swift, Mirage): Participants will be randomized to one of three pre-set CPAP pressures: less than 1 cm water (H₂O), 5 cm H₂O or 10 cm H₂O. They will be instructed to use the CPAP device every night for 12 weeks. Methacholine airways reactivity will be measured at the end of these 12 weeks and again after a 2-week washout period, 14 weeks after randomization.
|
CPAP 5cm H₂O
n=69 Participants
Continuous Positive Airway Pressure device (Resmed, Swift, Mirage): Participants will be randomized to one of three pre-set CPAP pressures: less than 1 cm water (H₂O), 5 cm H₂O or 10 cm H₂O. They will be instructed to use the CPAP device every night for 12 weeks. Methacholine airways reactivity will be measured at the end of these 12 weeks and again after a 2-week washout period, 14 weeks after randomization.
|
CPAP 10cm H₂O
n=59 Participants
Continuous Positive Airway Pressure device (Resmed, Swift, Mirage): Participants will be randomized to one of three pre-set CPAP pressures: less than 1 cm water (H₂O), 5 cm H₂O or 10 cm H₂O. They will be instructed to use the CPAP device every night for 12 weeks. Methacholine airways reactivity will be measured at the end of these 12 weeks and again after a 2-week washout period, 14 weeks after randomization.
|
Total
n=194 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
33 years
n=99 Participants
|
31 years
n=107 Participants
|
25 years
n=206 Participants
|
31 years
n=7 Participants
|
|
Sex: Female, Male
Female
|
42 Participants
n=99 Participants
|
35 Participants
n=107 Participants
|
36 Participants
n=206 Participants
|
113 Participants
n=7 Participants
|
|
Sex: Female, Male
Male
|
24 Participants
n=99 Participants
|
34 Participants
n=107 Participants
|
23 Participants
n=206 Participants
|
81 Participants
n=7 Participants
|
|
Region of Enrollment
United States
|
66 participants
n=99 Participants
|
69 participants
n=107 Participants
|
59 participants
n=206 Participants
|
194 participants
n=7 Participants
|
|
Asthma Symptom Utility Index (ASUI) Score
|
0.89 units on a scale
n=99 Participants
|
0.94 units on a scale
n=107 Participants
|
0.92 units on a scale
n=206 Participants
|
0.92 units on a scale
n=7 Participants
|
|
Asthma Control Test (ACT) Score
|
21 units on a scale
n=99 Participants
|
22 units on a scale
n=107 Participants
|
22 units on a scale
n=206 Participants
|
22 units on a scale
n=7 Participants
|
|
Marks Asthma Quality of Life
|
9 units on a scale
n=99 Participants
|
7 units on a scale
n=107 Participants
|
6 units on a scale
n=206 Participants
|
7 units on a scale
n=7 Participants
|
|
Sinonasal Questionnaire (SNQ-6)
|
0.8 units on a scale
n=99 Participants
|
0.8 units on a scale
n=107 Participants
|
0.8 units on a scale
n=206 Participants
|
0.8 units on a scale
n=7 Participants
|
|
PC20
|
1.06 mg/mL
n=99 Participants
|
0.96 mg/mL
n=107 Participants
|
0.89 mg/mL
n=206 Participants
|
0.98 mg/mL
n=7 Participants
|
|
FEV₁
|
2.9 L
n=99 Participants
|
3.1 L
n=107 Participants
|
3.0 L
n=206 Participants
|
3.1 L
n=7 Participants
|
|
Percent-predicted FEV₁
|
90.0 percent
n=99 Participants
|
90.9 percent
n=107 Participants
|
91.8 percent
n=206 Participants
|
90.6 percent
n=7 Participants
|
|
Forced vital capacity (FVC)
|
3.9 L
n=99 Participants
|
4.2 L
n=107 Participants
|
3.9 L
n=206 Participants
|
4.1 L
n=7 Participants
|
|
Daily use of inhaled corticosteroid (ICS)
|
11 participants
n=99 Participants
|
10 participants
n=107 Participants
|
10 participants
n=206 Participants
|
31 participants
n=7 Participants
|
|
Daily use of combined inhaled corticosteroid/long acting beta agonist (ICS/LABA)
|
18 participants
n=99 Participants
|
23 participants
n=107 Participants
|
13 participants
n=206 Participants
|
54 participants
n=7 Participants
|
|
Daily use of anti-leukotriene
|
8 participants
n=99 Participants
|
9 participants
n=107 Participants
|
5 participants
n=206 Participants
|
22 participants
n=7 Participants
|
|
BMI
|
25.8 kg/m^2
n=99 Participants
|
26.2 kg/m^2
n=107 Participants
|
24.1 kg/m^2
n=206 Participants
|
25.7 kg/m^2
n=7 Participants
|
|
Former smoker
|
12 participants
n=99 Participants
|
6 participants
n=107 Participants
|
5 participants
n=206 Participants
|
23 participants
n=7 Participants
|
PRIMARY outcome
Timeframe: 12 weeks after randomizationThe primary outcome measure was the change in provocative concentration of methacholine causing a 20% fall in forced expiratory volume in 1 second (FEV₁) (PC20) from baseline to 12 weeks. Modified American Thoracic Society guidelines were followed for pre-bronchodilator spirometry and methacholine challenge testing using the 5 breath dosimeter technique. Up to eleven doses, each a doubling concentration of methacholine (Provocholine™), were inhaled starting at 0.03 mg/mL until a 20% or greater fall in FEV₁ occurred; the maximum dose was 32 mg/mL. Breaths each of doubling concentrations of methacholine were inhaled from a calibrated DeVilbiss™ 646 nebulizer.
Outcome measures
| Measure |
CPAP Less Than 1 cm H2O
n=66 Participants
Continuous Positive Airway Pressure device (Resmed, Swift, Mirage): Participants will be randomized to one of three pre-set CPAP pressures: less than 1 cm water (H₂O), 5 cm H₂O or 10 cm H₂O. They will be instructed to use the CPAP device every night for 12 weeks. Methacholine airways reactivity will be measured at the end of these 12 weeks and again after a 2-week washout period, 14 weeks after randomization.
|
CPAP 5cm H2O
n=69 Participants
Continuous Positive Airway Pressure device (Resmed, Swift, Mirage): Participants will be randomized to one of three pre-set CPAP pressures: less than 1 cm water (H₂O), 5 cm H₂O or 10 cm H₂O. They will be instructed to use the CPAP device every night for 12 weeks. Methacholine airways reactivity will be measured at the end of these 12 weeks and again after a 2-week washout period, 14 weeks after randomization.
|
CPAP 10cm H2O
n=59 Participants
Continuous Positive Airway Pressure device (Resmed, Swift, Mirage): Participants will be randomized to one of three pre-set CPAP pressures: less than 1 cm water (H₂O), 5 cm H₂O or 10 cm H₂O. They will be instructed to use the CPAP device every night for 12 weeks. Methacholine airways reactivity will be measured at the end of these 12 weeks and again after a 2-week washout period, 14 weeks after randomization.
|
|---|---|---|---|
|
Methacholine Reactivity
PC20, 12-week
|
2.13 mg/mL
Interval 1.3 to 3.49
|
1.48 mg/mL
Interval 0.96 to 2.28
|
1.44 mg/mL
Interval 0.91 to 2.27
|
|
Methacholine Reactivity
PC20, post-washout (14 weeks)
|
1.60 mg/mL
Interval 0.96 to 2.69
|
1.37 mg/mL
Interval 0.91 to 2.07
|
1.27 mg/mL
Interval 0.81 to 2.01
|
Adverse Events
CPAP Less Than 1 cm H₂O
Serious events: 1 serious events
Other events: 34 other events
Deaths: 0 deaths
CPAP 5cm H₂O
Serious events: 1 serious events
Other events: 35 other events
Deaths: 0 deaths
CPAP 10cm H₂O
Serious events: 0 serious events
Other events: 25 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
CPAP Less Than 1 cm H₂O
n=58 participants at risk；n=66 participants at risk
Continuous Positive Airway Pressure device (Resmed, Swift, Mirage): Participants will be randomized to one of three pre-set CPAP pressures: less than 1 cm water (H₂O), 5 cm H₂O or 10 cm H₂O. They will be instructed to use the CPAP device every night for 12 weeks. Methacholine airways reactivity will be measured at the end of these 12 weeks and again after a 2-week washout period, 14 weeks after randomization.
|
CPAP 5cm H₂O
n=62 participants at risk；n=69 participants at risk
Continuous Positive Airway Pressure device (Resmed, Swift, Mirage): Participants will be randomized to one of three pre-set CPAP pressures: less than 1 cm water (H₂O), 5 cm H₂O or 10 cm H₂O. They will be instructed to use the CPAP device every night for 12 weeks. Methacholine airways reactivity will be measured at the end of these 12 weeks and again after a 2-week washout period, 14 weeks after randomization.
|
CPAP 10cm H₂O
n=57 participants at risk；n=59 participants at risk
Continuous Positive Airway Pressure device (Resmed, Swift, Mirage): Participants will be randomized to one of three pre-set CPAP pressures: less than 1 cm water (H₂O), 5 cm H₂O or 10 cm H₂O. They will be instructed to use the CPAP device every night for 12 weeks. Methacholine airways reactivity will be measured at the end of these 12 weeks and again after a 2-week washout period, 14 weeks after randomization.
|
|---|---|---|---|
|
Nervous system disorders
Ischemic stroke
|
1.5%
1/66 • Number of events 1
|
0.00%
0/69
|
0.00%
0/59
|
|
Renal and urinary disorders
Pyleonephritis
|
1.5%
1/66 • Number of events 1
|
0.00%
0/69
|
0.00%
0/59
|
|
Blood and lymphatic system disorders
Iron deficiency anemia
|
0.00%
0/66
|
1.4%
1/69 • Number of events 1
|
0.00%
0/59
|
Other adverse events
| Measure |
CPAP Less Than 1 cm H₂O
n=58 participants at risk；n=66 participants at risk
Continuous Positive Airway Pressure device (Resmed, Swift, Mirage): Participants will be randomized to one of three pre-set CPAP pressures: less than 1 cm water (H₂O), 5 cm H₂O or 10 cm H₂O. They will be instructed to use the CPAP device every night for 12 weeks. Methacholine airways reactivity will be measured at the end of these 12 weeks and again after a 2-week washout period, 14 weeks after randomization.
|
CPAP 5cm H₂O
n=62 participants at risk；n=69 participants at risk
Continuous Positive Airway Pressure device (Resmed, Swift, Mirage): Participants will be randomized to one of three pre-set CPAP pressures: less than 1 cm water (H₂O), 5 cm H₂O or 10 cm H₂O. They will be instructed to use the CPAP device every night for 12 weeks. Methacholine airways reactivity will be measured at the end of these 12 weeks and again after a 2-week washout period, 14 weeks after randomization.
|
CPAP 10cm H₂O
n=57 participants at risk；n=59 participants at risk
Continuous Positive Airway Pressure device (Resmed, Swift, Mirage): Participants will be randomized to one of three pre-set CPAP pressures: less than 1 cm water (H₂O), 5 cm H₂O or 10 cm H₂O. They will be instructed to use the CPAP device every night for 12 weeks. Methacholine airways reactivity will be measured at the end of these 12 weeks and again after a 2-week washout period, 14 weeks after randomization.
|
|---|---|---|---|
|
General disorders
Headache
|
30.0%
15/50 • Number of events 15
|
20.0%
11/55 • Number of events 11
|
30.4%
14/46 • Number of events 14
|
|
Social circumstances
Increased work breathing
|
5.5%
3/55 • Number of events 3
|
11.7%
7/60 • Number of events 7
|
5.4%
3/56 • Number of events 3
|
|
Respiratory, thoracic and mediastinal disorders
Acute upper respiratory tract infection
|
15.5%
9/58 • Number of events 9
|
11.3%
7/62 • Number of events 7
|
8.8%
5/57 • Number of events 5
|
|
General disorders
Drying of nose, mouth, and/or throat
|
18.2%
10/55 • Number of events 10
|
22.0%
13/59 • Number of events 13
|
14.5%
8/55 • Number of events 8
|
|
General disorders
Nose irritation
|
10.5%
6/57 • Number of events 6
|
14.8%
9/61 • Number of events 9
|
12.5%
7/56 • Number of events 7
|
|
Ear and labyrinth disorders
Ear or sinus discomfort
|
12.3%
7/57 • Number of events 7
|
13.3%
8/60 • Number of events 8
|
10.7%
6/56 • Number of events 6
|
|
General disorders
Congestion, runny nose, sneezing
|
40.4%
21/52 • Number of events 21
|
48.1%
25/52 • Number of events 25
|
30.4%
14/46 • Number of events 14
|
|
Eye disorders
Eye irritation
|
8.9%
5/56 • Number of events 5
|
6.6%
4/61 • Number of events 4
|
5.9%
3/51 • Number of events 3
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place