Predictor for an Additional Benefit of Inhaled Corticosteroid in Patients Treated With Tiotropium for COPD

• Sponsor: Cantonal Hosptal, Baselland (Other)
• Overall Status: Completed
• CT.gov ID: NCT00860938
• Collaborator: (none)
• Enrollment: 90
• Location: 1
• Arms: 2
• Duration (Months): 42
• Patients Per Site Per Month: 2.1

Study Details

Study Description

Brief Summary

Study purpose is to evaluate if subjects with chronic obstructive pulmonary disease (COPD) are more likely to be responsive to additional inhaled corticosteroids if they have a positive response to hyperosmolar challenge with mannitol than if their response is negative.

Condition or Disease	Intervention/Treatment	Phase
COPD	Drug: Budesonide	Phase 4

Detailed Description

In patients with chronic obstructive pulmonary disease (COPD), the treatment with inhaled corticosteroids (ICS) is controversial. Preliminary results of our recent pilot study in 30 COPD patients showed for the first time, that ICS response mey be predicted by a bronchoprovocation challenge test with mannitol. However, this finding needs to be proven in a placebo-controlled trial. For this cohort study, 100 corticosteroid-naive, non reversible (FEV1) patients with COPD will be recruited. Spirometry before and after bronchodilation will be measured at study entry and at four weeks run-in (only tiotropium) and at three month of treatment with tiotropium and ICS or placebo. Quality of life (St. George Respiratory Quality of Life Questionnaire) and exacerbation rate of COPD will be assessed. Measurement of exhaled nitric oxide and mannitol challenge will be performed at study entry and at 1 and 4 month. Primary endpoint will be improvement in FEV1 in each group (positive and negative mannitol challenge) after 3 months follow up. Secondary endpoints will be the difference in dose-response-curve in the mannitol challenge, exacerbation rate and change in quality of life after three month follow-up.

Study Design

• Study Type: Interventional
• Actual Enrollment: 90 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Predictor for an Additional Benefit of Inhaled Corticosteroid in Patients Treated With Tiotropium for Chronic Obstructive Pulmonary Disease (COPD)
• Study Start Date: Apr 1, 2007
• Actual Primary Completion Date: Aug 1, 2010
• Actual Study Completion Date: Oct 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Budesonide	Drug: Budesonide; After 4 weeks of inhalative therapy with tiotropium (all patients), patient get randomized to receive either inhalative budesonide (1600ug per day or placebo; Other Names: Miflonide
Placebo Comparator: Placebo	Drug: Budesonide; After 4 weeks of inhalative therapy with tiotropium (all patients), patient get randomized to receive either inhalative budesonide (1600ug per day or placebo; Other Names: Miflonide

Outcome Measures

Primary Outcome Measures

1. Change in Lung Function (FEV1) [12 weeks]

Secondary Outcome Measures

1. The Proportion Who Complete Follow-up Without Developing an Exacerbation [12 weeks]

2. Change in Quality of Life [12 weeks, baseline to 3 months follow-up]

   St. George Respiratory Questionnaire (SGRQ). Disease-specific instrument designed to measure impact on overall health, daily life, and perceived well-being in patients with obstructive airways disease. Scores are calculated for three domains: Part I (Symptoms): several scales; Part II (Activity and Impacts): dichotomous (true/false) except last question (4-point Likert scale) Scores range from 0 to 100, with higher scores indicating more limitations. Unit of Measure = Units on a scale A minimum change in score of 4 units was established as clinically relevant after patient and clinician testing. Based on empirical data and interviews with patients, a mean change score of 4 units is associated with slightly efficacious treatment, 8 units for moderately efficacious change and 12 units for very efficacious treatment. The higher the change in units, the better the treatment.

3. Change in logRDR Mannitol [12 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• FEV1/FVC < 70%

• FEV1 % predicted > 60%

Exclusion Criteria:

• Other major disease

• Asthma

• Currently taking inhaled corticosteroids

• oral corticosteroids in the last 3 month

• significant cardiovascular disease

• pregnancy/breast feeding

• current use of salmeterol or other long acting bronchodilator

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Hospital Basel	Basel		Switzerland	4031

Sponsors and Collaborators

• Cantonal Hosptal, Baselland

Investigators

• Principal Investigator: Jörg D Leuppi, MD PhD, University Hospital, Basel, Switzerland

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Prof. Dr. Jörg Leuppi, Prof. Dr., Cantonal Hosptal, Baselland
• ClinicalTrials.gov Identifier: NCT00860938
• Other Study ID Numbers: EKBB 148/06
• First Posted: Mar 13, 2009
• Last Update Posted: Jul 23, 2019
• Last Verified: Jul 1, 2019

• Keywords provided by Prof. Dr. Jörg Leuppi, Prof. Dr., Cantonal Hosptal, Baselland: Inhaled corticosteroids; COPD; mannitol
• Additional relevant MeSH terms: Respiratory Aspiration; Budesonide

Study Results

Participant Flow

Recruitment Details	out patient clinic
Pre-assignment Detail	run-in

Arm/Group Title	Budesonide	Placebo
Arm/Group Description
Period Title: Overall Study
STARTED	45	45
COMPLETED	31	37
NOT COMPLETED	14	8

Baseline Characteristics

Arm/Group Title	Budesonide	Placebo	Total
Arm/Group Description	Total of all reporting groups
Overall Participants	31	37	68
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	13 41.9%	14 37.8%	27 39.7%
>=65 years	18 58.1%	23 62.2%	41 60.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60 (16)	62 (22)	61.5 (20)
Sex: Female, Male (Count of Participants)
Female	12 38.7%	19 51.4%	31 45.6%
Male	19 61.3%	18 48.6%	37 54.4%
Region of Enrollment (participants) [Number]
Switzerland	31 100%	37 100%	68 100%
FEV1/FVC (%) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [%]	63 (10)	64 (10)	64 (10)

Outcome Measures

1. Primary Outcome

Title	Change in Lung Function (FEV1)
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

per protocol

Arm/Group Title	Budesonide	Placebo
Arm/Group Description
Measure Participants	31	37
Mean (Standard Deviation) [litres]	0.05 (0.01)	-0.05 (0.01)

2. Secondary Outcome

Title	The Proportion Who Complete Follow-up Without Developing an Exacerbation
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Budesonide	Placebo
Arm/Group Description
Measure Participants	31	37
Number [number of participants]	31 100%	37 100%

3. Secondary Outcome

Title	Change in Quality of Life
Description	St. George Respiratory Questionnaire (SGRQ). Disease-specific instrument designed to measure impact on overall health, daily life, and perceived well-being in patients with obstructive airways disease. Scores are calculated for three domains: Part I (Symptoms): several scales; Part II (Activity and Impacts): dichotomous (true/false) except last question (4-point Likert scale) Scores range from 0 to 100, with higher scores indicating more limitations. Unit of Measure = Units on a scale A minimum change in score of 4 units was established as clinically relevant after patient and clinician testing. Based on empirical data and interviews with patients, a mean change score of 4 units is associated with slightly efficacious treatment, 8 units for moderately efficacious change and 12 units for very efficacious treatment. The higher the change in units, the better the treatment.
Time Frame	12 weeks, baseline to 3 months follow-up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Budesonide	Placebo
Arm/Group Description
Measure Participants	31	37
Mean (Standard Deviation) [units]	5.1 (5.8)	1.8 (0.3)

4. Secondary Outcome

Title	Change in logRDR Mannitol
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Budesonide	Placebo
Arm/Group Description
Measure Participants	31	37
Mean (Standard Deviation) [%/mg]	0.12 (0.1)	-0.09 (0.01)

Adverse Events

Arm/Group Title	Budesonide		Placebo
Arm/Group Description
All Cause Mortality
	Budesonide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Budesonide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/31 (3.2%)		2/37 (5.4%)
Cardiac disorders
unstable angina pectoris	1/31 (3.2%)		2/37 (5.4%)
Renal and urinary disorders
Urosepsis	1/31 (3.2%)		2/37 (5.4%)
Other (Not Including Serious) Adverse Events
	Budesonide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/31 (6.5%)		2/37 (5.4%)
Respiratory, thoracic and mediastinal disorders
Acute exacerbation	2/31 (6.5%)		2/37 (5.4%)

Limitations/Caveats

The dropout rate of 24% was relatively high. A further limitation of the study might be the lack of data for sputum eosinophilia.

More Information

Certain Agreements

All Principal Investigators ARE 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.