WSMR2: Comparing Bronchodilation of Symbicort With and Without Valved Holding Chamber (Aerochamber Plus)

• Sponsor: Western Sky Medical Research (Other)
• Overall Status: Completed
• CT.gov ID: NCT00915538
• Collaborator: AstraZeneca (Industry)
• Enrollment: 16
• Location: 1
• Arms: 2
• Duration (Months): 1
• Patients Per Site Per Month: 15.7

Study Details

Study Description

Brief Summary

This study will compare the amount of bronchial tube relaxation from the Formoterol medicine contained in the Symbicort pressure Metered Dose Inhaler(pMDI)(a combination of Budesonide, a steroid, and Formoterol, a drug which relaxes the bronchial smooth muscle. The comparison will be using the pMDI in the usual fashion to the pMDIs and a spacer which allows more time for breathing in the medication. Breathing tests will be measured over a 12 hour period for the comparison.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: pMDI budesonide/formotrol 160/4.5 is in group 1; Device: Symbicort 160/4.5 plus Aerochamber Plus included in group 2	Phase 4

Detailed Description

Sixteen subjects will receive treatment in a cross-over design. They will inhale Symbicort 160/4.5 two inhalations in the manner prescribed in the approved package insert. The second intervention will be the inhalation of Symbicort 160/4.5 two inhalations through a valved holding chamber (Aero Chamber Plus). Breathing tests including spirometry will be measured at various time periods over a 12-hour time frame in each intervention. Comparison will be made of the two periods to demonstrate that the use of the valved holding chamber does not adversely affect the bronchodilation of the formoterol component of the combination drug.

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: A Comparison of the Bronchodilating Activity of Symbicort Pressure Metered Dose Inhaler (pMDI) 160/4.5 Used in the Conventional Manner and With a Valved Spacer Holding Chamber (Aerochamber Plus)
• Study Start Date: Jul 1, 2009
• Actual Primary Completion Date: Aug 1, 2009
• Actual Study Completion Date: Aug 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Other: Group 1 / use of pMDI as approved The intervention in this group will use inhalation from the pMDI containing budesonide/formoterol pMDI 160/4.5 2 inhalations as approved. (FDA approved product information) without a spacer. The pulmonary function tests (PFTs) will be collected at baseline and for a period of 12 hours post inhalation of 2 inhalation of budesonide /formoterol; pMDI160/5.	Drug: pMDI budesonide/formotrol 160/4.5 is in group 1; The asthmatic subjects will receive budesonide/formoterol pMDI 160/4.5 pMDI 2 inhalations used in conventional fashion, and have pulmonary function measured over 12 hours who are expected to show bronchodilation.; Other Names: Symbicort ; Device: Symbicort 160/4.5 plus Aerochamber Plus included in group 2; Symbicort 160/4.5 2 inhalations will be administered through a valved holding chamber, Aerochamber Plus, Pulmonary functions will be measured over 12 hours in asthmatic subjects who are expected to show bronchodilation.; Other Names: Symbicort Aerochamber plus
Experimental: Group 2 / pMDI with Aerochamber Plus The intervention in this group will use the pMDI budesonide/formoterol 160/4.5 with a valve holding chamber spacer device, Aerochamber Plus which is the intervention being studied The PFTs will be collected at baseline and for a period of 12 hours post inhalation of 2 inhalation of Symbicort 160/5. This is the intervention to be studied for comparison to the non-spacer inhalations..	Drug: pMDI budesonide/formotrol 160/4.5 is in group 1; The asthmatic subjects will receive budesonide/formoterol pMDI 160/4.5 pMDI 2 inhalations used in conventional fashion, and have pulmonary function measured over 12 hours who are expected to show bronchodilation.; Other Names: Symbicort ; Device: Symbicort 160/4.5 plus Aerochamber Plus included in group 2; Symbicort 160/4.5 2 inhalations will be administered through a valved holding chamber, Aerochamber Plus, Pulmonary functions will be measured over 12 hours in asthmatic subjects who are expected to show bronchodilation.; Other Names: Symbicort Aerochamber plus

Outcome Measures

Primary Outcome Measures

1. The Mean Area Under the Curve (AUC) of Forced Expiratory Volume in One Second (FEV-1) Over 12 Hours, Measured (BL), 5, 10, 15, 60, 120, 240, 480, 720 Minutes. The Unit is Liters, and the AUC is in Liters. [BL, 5, 10,15,30,60,120,240,480,720 minutes (12 hrs)]

   The mean FEV-1 (Forced Expiratory Volume 1 second) for each of the treatments (with and without valved holding chamber) in this crossover design were recorded at BL, 5, 10, 15, 30, 60, 120, 240. 480, 720 minutes (12 hrs) were plotted as a curve and the area under the curve was calculated. The measured results was mean liters/12 hours.

Secondary Outcome Measures

1. FEV-1/FVC [0,5,10,15,30,60,120,240,480,720 minutes]

   The ratio of the volumes in liters of FEV-1 to Forced vital capacity (FVC). This is reported as percent for each time point., Each time point will be compared.for the two interventions. This expressed as a percentage.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Asthma with 15% or more increase in Forced expiratory volume at 1 second (FEV-1) after 180-360 mcg of albuterol pMDI

Exclusion Criteria:

• Any illness or condition which might place subject at risk in the study;e.g. some cardiovascular disorders Inability to understand and sign informed consent

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Western Sky Medical Research	El Paso	Texas	United States	79903

Sponsors and Collaborators

• Western Sky Medical Research
• AstraZeneca

Investigators

• Principal Investigator: Lyndon E Mansfield, MD, Western Sky Medical Research

Study Documents (Full-Text)

None provided.

More Information

Publications

• Dolovich MB, Ahrens RC, Hess DR, Anderson P, Dhand R, Rau JL, Smaldone GC, Guyatt G; American College of Chest Physicians; American College of Asthma, Allergy, and Immunology. Device selection and outcomes of aerosol therapy: Evidence-based guidelines: American College of Chest Physicians/American College of Asthma, Allergy, and Immunology. Chest. 2005 Jan;127(1):335-71. Review.
• Hess DR. Aerosol delivery devices in the treatment of asthma. Respir Care. 2008 Jun;53(6):699-723; discussion 723-5.
• Newman SP. Principles of metered-dose inhaler design. Respir Care. 2005 Sep;50(9):1177-90. Review.

• Responsible Party: Lyndon Mansfield, Director, Western Sky Medical Research
• ClinicalTrials.gov Identifier: NCT00915538
• Other Study ID Numbers: WSMR 2008-2
• First Posted: Jun 8, 2009
• Last Update Posted: Aug 13, 2020
• Last Verified: Aug 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Lyndon Mansfield, Director, Western Sky Medical Research: Asthma; Formoterol; Long Acting Beta Adrenergic Bronchodilator; Symbicort; Aerochamber
• Additional relevant MeSH terms: Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination

Study Results

Participant Flow

Arm/Group Title	Conventional First	Spacer First
Arm/Group Description	This group will use pMDI in usual fashion first and cross over to pMDI and valved holding chamber	This arm will receive pMDI and Valved holding chamber on fist day. On anther day will receive pMDI in usual fashion. Pulmonary functions wil be measured over 12 hours
Period Title: Overall Study
STARTED	8	8
COMPLETED	8	8
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Conventional First	Spacer First	Total
Arm/Group Description	This group will use pMDI in usual fashion first and cross over to pMDI and valved holding chamber	This arm will receive pMDI and Valved holding chamber on fist day. On anther day will receive pMDI in usual fashion. Pulmonary functions wil be measured over 12 hours	Total of all reporting groups
Overall Participants	8	8	16
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	8 100%	8 100%	16 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	37 (7)	36 (7)	36.5 (7)
Sex: Female, Male (Count of Participants)
Female	3 37.5%	4 50%	7 43.8%
Male	5 62.5%	4 50%	9 56.3%
Region of Enrollment (participants) [Number]
United States	8 100%	8 100%	16 100%

Outcome Measures

1. Primary Outcome

Title	The Mean Area Under the Curve (AUC) of Forced Expiratory Volume in One Second (FEV-1) Over 12 Hours, Measured (BL), 5, 10, 15, 60, 120, 240, 480, 720 Minutes. The Unit is Liters, and the AUC is in Liters.
Description	The mean FEV-1 (Forced Expiratory Volume 1 second) for each of the treatments (with and without valved holding chamber) in this crossover design were recorded at BL, 5, 10, 15, 30, 60, 120, 240. 480, 720 minutes (12 hrs) were plotted as a curve and the area under the curve was calculated. The measured results was mean liters/12 hours.
Time Frame	BL, 5, 10,15,30,60,120,240,480,720 minutes (12 hrs)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1	Group 2
Arm/Group Description	The intervention in this group will inhalation from the pMDI containing budesonide/formoterol pMDI 160/4,5 2 inhalations as recommended in product PI (FDA approved product information)without a spacer. The pulmonary function tests (PFTs) will be collected at baseline and for a period of 12 hours post inhalation of 2 inhalation of budesonide /formoterol; pMDI160/5. pMDI budesonide/formotrol 160/4.5 is in group 1: The subjects will receive budesonide/formoterol pMDI 160/4.5 pMDI used in conventional fashion, and have pulmonary function measured over 12 hours. Symbicort 160/4.5 plus Aerochamber Plus icluded in group 2: Symbicort 160/4.5 will be administered through a valved holding chamber, Pulmonary functions will be measured over 12 hours.	The intervention in this group will use the pMDI budesonide/formoterol 160/4.5 with a valve holding chamber spacer device (aerochamber plus)which is the intervention being studied The PFTs will be collected at baseline and for a period of 12 hours post inhalation of 2 inhalation of Symbicort 160/5. This is the intervention to be studied for comparison to the non-spacer inhalations.. pMDI budesonide/formotrol 160/4.5 is in group 1: The subjects will receive budesonide/formoterol pMDI 160/4.5 pMDI used in conventional fashion, and have pulmonary function measured over 12 hours. Symbicort 160/4.5 plus Aerochamber Plus icluded in group 2: Symbicort 160/4.5 will be administered through a valved holding chamber, Pulmonary functions will be measured over 12 hours.
Measure Participants	16	16
Mean (Full Range) [Liters X hours]	2.77	2.79

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1, Group 2
	Comments	The cross-over means there were 16 determinants for each time for each treatment. The AUC of FEV-1 was measured in each subject for each treatment arm and the mean of this data was compared.
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	The expected results for non-inferiority would be +/- 5% of difference between the two groups in the primary efficacy parameter.
Statistical Test of Hypothesis	p-Value	0.76
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	AUC
	Estimated Value	0.0
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Group 1, Group 2
	Comments
	Type of Statistical Test	Other
	Comments	Two sample T test
Statistical Test of Hypothesis	p-Value	>.05
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 12
	Estimation Comments

2. Secondary Outcome

Title	FEV-1/FVC
Description	The ratio of the volumes in liters of FEV-1 to Forced vital capacity (FVC). This is reported as percent for each time point., Each time point will be compared.for the two interventions. This expressed as a percentage.
Time Frame	0,5,10,15,30,60,120,240,480,720 minutes

Outcome Measure Data

Analysis Population Description

This is a cross over design. 2 cohorts of 8 subjects will be tested in a cross over design, so that 16 measurements will be made for each intervention. This should give power of 0.8 for non inferiority equivalence study.

Arm/Group Title	Spacer	Non-Spacer (Conventional)
Arm/Group Description	This arm will receive pMDI Symbicort 160/4.5 with an Aerochamber Plus Valved holding chamber.	This arm will receive pMDI Symbicort 160/4.5 without an Aerochamber.
Measure Participants	16	16
0 time	76.13 (11.7)	75.58 (12.5)
5 minutes	79.08 (12.07)	79.91 (14.33)
10 minutes	78.55 (13.53)	81.16 (15.08)
15 minutes	79.08 (10.80)	80.29 (13.13)
30 minutes	80.17 (14.32)	80.55 (15.11)
60 minutes	78.05 (15.30)	81.63 (14.63)
120 minutes	80.94 (13.95)	81.40 (15.97)
240 minutes	81.56 (14.30)	82.42 (13.75)
480 minutes	79.95 (14.43)	80.56 (13.94)
720 minutes	79.93 (12.54)	80.33 (13.36)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1
	Comments	The cross over means there were 16 determinants for each time for each treatment
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	Power calculation was not done for secondary parameter. The comparison was for the FEV-1/FVC expressed as fraction at each time point
Statistical Test of Hypothesis	p-Value	0.76
	Comments
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	Adverse events were collected during a period of two weeks (the study duration).
Adverse Event Reporting Description	No source vocabulary was used as there were no adverse events to record. No table was formed because of no data.
Arm/Group Title	Conventional		Spacer
Arm/Group Description	This group will use pMDI in usual fashion		This arm will receive pMDI and Valved holding chamber
All Cause Mortality
	Conventional		Spacer
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Conventional		Spacer
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/16 (0%)
Other (Not Including Serious) Adverse Events
	Conventional		Spacer
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/16 (0%)

Limitations/Caveats

No subject discontinued subjects were adults experienced in using a pressured metered dose inhaler (pMDI), Spacers or holding chambers are most frequently used by patients with coordination difficulties.

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.