Effect of Positive Airway Pressure on Reducing Airway Reactivity in Patients With Asthma (CPAP) (CPAP)

• ClinicalTrials.gov Identifier: NCT01629823
• Recruitment Status: Completed
• First Posted: June 28, 2012
• Results First Posted: May 15, 2017
• Last Update Posted: May 15, 2017
• Sponsor: American Lung Association Asthma Clinical Research Centers
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Information provided by (Responsible Party): Robert A. Wise, M.D., American Lung Association Asthma Clinical Research Centers

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Asthma
• Intervention: Device: Continuous Positive Airway Pressure device (Resmed, Swift, Mirage)
• Enrollment: 209

Participant Flow

Recruitment Details
Pre-assignment Details	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

Arm/Group Title	CPAP Less Than 1 cm Water (H₂O)	CPAP 5cm H₂O	CPAP 10cm H₂O
Arm/Group Description	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.	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.	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.
Period Title: Trial Period
Started	66	69	59
Completed	53	56	49
Not Completed	13	13	10
Reason Not Completed
Missed visit	11	9	8
Pre-diluent FEV₁ predicted <70%	1	1	1
Pregnancy	1	0	0
Adverse Event	0	1	0
Out-of-window visit	0	2	0
Failed to hold medication	0	0	1
Period Title: Washout Period
Started	54	57	50
Completed	51	51	50
Not Completed	3	6	0
Reason Not Completed
Safety	2	5	0
Pregnancy	1	0	0
Protocol Violation	0	1	0

Baseline Characteristics

Arm/Group Title		CPAP Less Than 1 cm H₂O	CPAP 5cm H₂O	CPAP 10cm H₂O	Total
Arm/Group Description		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.	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.	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 of all reporting groups
Overall Number of Baseline Participants		66	69	59	194
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Median (Inter-Quartile Range); Unit of measure: Years
	Number Analyzed	66 participants	69 participants	59 participants	194 participants
		33; (23 to 47)	31; (20 to 40)	25; (18 to 39)	31; (20 to 41)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	66 participants	69 participants	59 participants	194 participants
	Female	42 63.6%	35 50.7%	36 61.0%	113 58.2%
	Male	24 36.4%	34 49.3%	23 39.0%	81 41.8%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	66 participants	69 participants	59 participants	194 participants
		66	69	59	194
Asthma Symptom Utility Index (ASUI) Score [1]; Median (Inter-Quartile Range); Unit of measure: Units on a scale
	Number Analyzed	66 participants	69 participants	59 participants	194 participants
		0.89; (0.83 to 0.94)	0.94; (0.85 to 1.00)	0.92; (0.86 to 0.98)	0.92; (0.84 to 0.98)
		[1] Measure Description: The Asthma Symptom Utility Index (ASUI) is a brief, interviewer-administered, patient preference-based scale assessing frequency and severity of selected asthma-related symptoms and treatment side effects. The minimum score is 0 and the maximum score is 1, with lower scores indicating more symptoms.
Asthma Control Test (ACT) Score [1]; Median (Inter-Quartile Range); Unit of measure: Units on a scale
	Number Analyzed	66 participants	69 participants	59 participants	194 participants
		21; (19 to 23)	22; (20 to 24)	22; (20 to 23)	22; (20 to 23)
		[1] Measure Description: The Asthma Control Test (ACT) is a validated self-administered survey utilizing 5 questions to assess asthma control on a scale from 1 (poor control) to 5 (total control) in individuals 12 years and older. By answering all 5 questions a patient with asthma can obtain a score that may range between 5 and 25. Asthma control is considered a good characteristic for a person with asthma and therefore a higher score is considered a better outcome.
Marks Asthma Quality of Life [1]; Median (Inter-Quartile Range); Unit of measure: Units on a scale
	Number Analyzed	66 participants	69 participants	59 participants	194 participants
		9; (5 to 21)	7; (3 to 11)	6; (3 to 10)	7; (4 to 12)
		[1] Measure Description: Marks Asthma Quality of Life Questionnaire (AQLQ) measures physical and emotional asthma specific quality of life during the past four weeks. The minimum score is 0 and the maximum score is 80, with lower scores indicating better quality of life. The scale is for use in adults only (individuals aged 18 or older).
Sinonasal Questionnaire (SNQ-6) [1]; Median (Inter-Quartile Range); Unit of measure: Units on a scale
	Number Analyzed	66 participants	69 participants	59 participants	194 participants
		0.8; (0.6 to 1.6)	0.8; (0.4 to 1.4)	0.8; (0.4 to 1.2)	0.8; (0.4 to 1.4)
		[1] Measure Description: The Sinonasal Questionnaire (SNQ-6) is a six-item questionnaire designed to diagnose chronic sinonasal disease in patients with asthma. This questionnaire asks about runny nose, postnasal drip, need to blow the nose, facial pain or pressure, and nasal obstruction. Possible answers include never (zero points), 1-4 times per month (1 point), 2-6 times per week (2 points), and daily (3 points). The number of points is then averaged. The minimum score is 0 and the maximum score is 3, with higher scores indicating higher frequency of sinonasal disease symptoms.
PC20 [1]; Median (Inter-Quartile Range); Unit of measure: mg/mL
	Number Analyzed	66 participants	69 participants	59 participants	194 participants
		1.06; (0.47 to 2.95)	0.96; (0.30 to 2.66)	0.89; (0.28 to 2.33)	0.98; (0.33 to 2.74)
		[1] Measure Description: The PC20 is the concentration of methacholine needed to produce a 20% fall in forced expiratory volume in 1 second (FEV₁) from baseline.
FEV₁ [1]; Median (Inter-Quartile Range); Unit of measure: L
	Number Analyzed	66 participants	69 participants	59 participants	194 participants
		2.9; (2.4 to 3.5)	3.1; (2.6 to 3.7)	3.0; (2.7 to 3.4)	3.1; (2.6 to 3.6)
		[1] Measure Description: FEV₁ stands for forced expiratory volume in one second, the volume that has been exhaled at the end of the first second of forced expiration.
Percent-predicted FEV₁; Median (Inter-Quartile Range); Unit of measure: Percent
	Number Analyzed	66 participants	69 participants	59 participants	194 participants
		90.0; (84.0 to 96.3)	90.9; (81.9 to 99.9)	91.8; (80.7 to 98.0)	90.6; (82.7 to 97.9)
Forced vital capacity (FVC) [1]; Median (Inter-Quartile Range); Unit of measure: L
	Number Analyzed	66 participants	69 participants	59 participants	194 participants
		3.9; (3.3 to 4.5)	4.2; (3.5 to 4.9)	3.9; (3.4 to 4.5)	4.1; (3.4 to 4.7)
		[1] Measure Description: Forced vital capacity: the determination of the vital capacity from a maximally forced expiratory effort.
Daily use of inhaled corticosteroid (ICS); Measure Type: Number; Unit of measure: Participants
	Number Analyzed	66 participants	69 participants	59 participants	194 participants
		11	10	10	31
Daily use of combined inhaled corticosteroid/long acting beta agonist (ICS/LABA); Measure Type: Number; Unit of measure: Participants
	Number Analyzed	66 participants	69 participants	59 participants	194 participants
		18	23	13	54
Daily use of anti-leukotriene; Measure Type: Number; Unit of measure: Participants
	Number Analyzed	66 participants	69 participants	59 participants	194 participants
		8	9	5	22
BMI; Median (Inter-Quartile Range); Unit of measure: Kg/m^2
	Number Analyzed	66 participants	69 participants	59 participants	194 participants
		25.8; (23.0 to 29.8)	26.2; (22.3 to 28.9)	24.1; (22.0 to 28.8)	25.7; (22.3 to 29.0)
Former smoker; Measure Type: Number; Unit of measure: Participants
	Number Analyzed	66 participants	69 participants	59 participants	194 participants
		12	6	5	23

Outcome Measures

1. Primary Outcome

Title	Methacholine Reactivity
Description	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.
Time Frame	12 weeks after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CPAP Less Than 1 cm H2O	CPAP 5cm H2O	CPAP 10cm H2O
Arm/Group Description:	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.	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.	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.
Overall Number of Participants Analyzed	66	69	59
Geometric Mean (95% Confidence Interval); Unit of Measure: mg/mL
PC20, 12-week	2.13; (1.30 to 3.49)	1.48; (0.96 to 2.28)	1.44; (0.91 to 2.27)
PC20, post-washout (14 weeks)	1.60; (0.96 to 2.69)	1.37; (0.91 to 2.07)	1.27; (0.81 to 2.01)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CPAP Less Than 1 cm H2O, CPAP 5cm H2O
	Comments	Both the 5 and 10cm groups were compared to the control group, <1cm H₂O
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.51
	Comments	Comparison of 5cm group to control. No adjustment for multiple comparisons.
	Method	Regression, Linear
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.81
	Confidence Interval	(2-Sided) 95%; 0.44 to 1.50
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	CPAP Less Than 1 cm H2O, CPAP 10cm H2O
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.57
	Comments	[Not Specified]
	Method	Regression, Linear
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.84
	Confidence Interval	(2-Sided) 95%; 0.47 to 1.52
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	CPAP Less Than 1 cm H₂O		CPAP 5cm H₂O		CPAP 10cm H₂O
Arm/Group Description	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.		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.		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.
All-Cause Mortality
	CPAP Less Than 1 cm H₂O		CPAP 5cm H₂O		CPAP 10cm H₂O
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--		--/--
Serious Adverse Events
	CPAP Less Than 1 cm H₂O		CPAP 5cm H₂O		CPAP 10cm H₂O
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/66 (1.52%)		1/69 (1.45%)		0/59 (0.00%)
Blood and lymphatic system disorders
Iron deficiency anemia [1]	0/66 (0.00%)	0	1/69 (1.45%)	1	0/59 (0.00%)	0
Nervous system disorders
Ischemic stroke [2]	1/66 (1.52%)	1	0/69 (0.00%)	0	0/59 (0.00%)	0
Renal and urinary disorders
Pyleonephritis [3]	1/66 (1.52%)	1	0/69 (0.00%)	0	0/59 (0.00%)	0
[1] Hospitalization due to chronic blood loss and fatigue; [2] Stroke; [3] Kidney infection
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	CPAP Less Than 1 cm H₂O		CPAP 5cm H₂O		CPAP 10cm H₂O
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	34/58 (58.62%)		35/62 (56.45%)		25/57 (43.86%)
Ear and labyrinth disorders
Ear or sinus discomfort	7/57 (12.28%)	7	8/60 (13.33%)	8	6/56 (10.71%)	6
Eye disorders
Eye irritation	5/56 (8.93%)	5	4/61 (6.56%)	4	3/51 (5.88%)	3
General disorders
Headache	15/50 (30.00%)	15	11/55 (20.00%)	11	14/46 (30.43%)	14
Drying of nose, mouth, and/or throat	10/55 (18.18%)	10	13/59 (22.03%)	13	8/55 (14.55%)	8
Nose irritation	6/57 (10.53%)	6	9/61 (14.75%)	9	7/56 (12.50%)	7
Congestion, runny nose, sneezing	21/52 (40.38%)	21	25/52 (48.08%)	25	14/46 (30.43%)	14
Respiratory, thoracic and mediastinal disorders
Acute upper respiratory tract infection	9/58 (15.52%)	9	7/62 (11.29%)	7	5/57 (8.77%)	5
Social circumstances
Increased work breathing	3/55 (5.45%)	3	7/60 (11.67%)	7	3/56 (5.36%)	3

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Janet T Holbrook, PhD, MPH
• Organization: ALA-ACRC
• Phone: 443-287-3170
• EMail: jholbro1@jhu.edu

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Holbrook JT, Sugar EA, Brown RH, Drye LT, Irvin CG, Schwartz AR, Tepper RS, Wise RA, Yasin RZ, Busk MF; American Lung Association Airways Clinical Research Centers. Effect of Continuous Positive Airway Pressure on Airway Reactivity in Asthma. A Randomized, Sham-controlled Clinical Trial. Ann Am Thorac Soc. 2016 Nov;13(11):1940-1950. doi: 10.1513/AnnalsATS.201601-043OC.

• Responsible Party: Robert A. Wise, M.D., American Lung Association Asthma Clinical Research Centers
• ClinicalTrials.gov Identifier: NCT01629823
• Other Study ID Numbers: ALA-ACRC-13; U01HL108730 ( U.S. NIH Grant/Contract )
• First Submitted: June 25, 2012
• First Posted: June 28, 2012
• Results First Submitted: January 30, 2017
• Results First Posted: May 15, 2017
• Last Update Posted: May 15, 2017