Study to Assess the Effect of Salbutamol and Ipratropium Bromide in Chronic Obstructive Pulmonary Disease (COPD) Patients

Sponsor

University Hospital, Antwerp (Other)

Overall Status

Completed

CT.gov ID

NCT00911651

Collaborator

GlaxoSmithKline (Industry)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The objectives of this study are to assess the effect of salbutamol in comparison with ipratropium bromide on the geometry of central and peripheral airways and to correlate spirometric indices with the Computational Fluid Dynamics (CFD) based calculated airway volumes and resistances for both compounds.

Condition or Disease	Intervention/Treatment	Phase
COPD	Drug: Salbutamol Drug: ipratropium bromide	Phase 4

Detailed Description

Salbutamol (VentolinTM) is a short acting beta agonist (SABA) which is used to treat wheezing, dyspnea and breathing difficulties caused by asthma and COPD. Further, it is also used to prevent bronchospasm during exercise.

Ipratropium bromide (Atrovent® HFA) is a short acting anticholinergic bronchodilator (short acting muscarinic antagonist (SAMA)) that improves lung function, dyspnea, exercise tolerance and health-related quality of life in patients with COPD. Studies have also shown that ipratropium bromide might reduce COPD exacerbations and related hospitalisations because the extended bronchodilatation might reduce infection rates by improving clearance of respiratory secretions.

In this open, randomized, two-way crossover, pilot study the effect of salbutamol in patients with moderate and severe COPD will be examined in comparison with the effects of ipratropium bromide. These patients will receive 400 µg salbutamol and 80 µg ipratropium bromide in a randomized crossover design.

The objectives of this study are to assess the effect of salbutamol in comparison with ipratropium bromide on the geometry of central and peripheral airways and to correlate spirometric indices (as Forced Expiratory Volume in one second (FEV1) and Tiffeneau index) with the Computational Fluid Dynamics (CFD) based calculated airway volumes and resistances for both compounds.

Study Design

Study Type:

Interventional

Actual Enrollment :

6 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Open, Randomized, Two-Way Crossover, Pilot Study to Assess the Effect of Salbutamol in Comparison With Ipratropium Bromide on Central and Peripheral Airway Dimensions in COPD Patients

Study Start Date :

Jun 1, 2008

Actual Primary Completion Date :

Jul 1, 2008

Actual Study Completion Date :

Aug 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: salbutamol 6 patients with moderate (GOLD 2) and severe (GOLD 3) COPD	Drug: Salbutamol 400 µg inhalation once Other Names: Ventolin
Active Comparator: ipratropium bromide COPD patients GOLD stage II and III	Drug: ipratropium bromide 80 µg inhalation once Other Names: atrovent

Arm

Intervention/Treatment

Active Comparator: salbutamol

6 patients with moderate (GOLD 2) and severe (GOLD 3) COPD

Drug: Salbutamol

400 µg inhalation once

Other Names:

Ventolin

Active Comparator: ipratropium bromide

COPD patients GOLD stage II and III

Drug: ipratropium bromide

80 µg inhalation once

Other Names:

atrovent

Outcome Measures

Primary Outcome Measures

The primary objective of this study is to assess the effect of a single dose of salbutamol in comparison with ipratropium bromide on central and peripheral small airways with high-resolution/multislice CT scan imaging technique. [1 month]

Secondary Outcome Measures

The secondary objectives are to evaluate effects on spirometric indices to correlate these with the CFD based calculated airway volumes and resistances for both compounds and to evaluate the safety of the products. [1 month]

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients with documented COPD based on the following criteria:

Smoking history of at least 10 pack-years.
Decreased Tiffeneau index (FEV1/(F)VC < 0.70).

Patients aged ≥ 40 years.
Patients should present moderate to severe COPD with an FEV1 between 30 and 80% of predicted (GOLD 2 and 3).
Patients should be treated according to GOLD guidelines.
Able to inhale study drug.
Maintained on stable respiratory medications for 6 weeks prior to visit 1.
Able to perform lung function tests.
Able to follow study procedures.

Exclusion Criteria:

Patients who are allergic to salbutamol, ipratropium bromide or to another element of the product.
Patients allergic to sojalecithin and products on the basis of soja and peanut.
Patients who have or ever had glaucoma.
Patients with urinary problems, prostate hyperplasy or bladder-neck obstruction. Patients whose symptoms are controlled on treatment may be included.
Patients with a recent history (i.e. six months or less) of myocardial infarction.
Patients with any unstable or life threatening cardiac arrhythmia.
Patients with severe kidney insufficiency (creatinine clearance ≤50 ml/min)a.
Patients below the age of 40.
Patients who are pregnant or are breast-feeding.
Patients who are treated with other anticholinergic medications, that cannot be stopped during the study period.
A respiratory infection or exacerbation of COPD in the four weeks prior to screening.
Significant alcohol or drug abuse within the past 12 months.
Participation in another trial with an investigational drug within one month or six half lives (whichever is greater) prior to screening visit.
Known active tuberculosis.
A history of asthma, cystic fibrosis, central bronchiectasis, interstitial lung disease or pulmonary thromboembolic disease.
A history of thoracotomy with pulmonary resection.
Active or untreated malignancy.
Use of oral corticosteroid medication at unstable doses (i.e. less than six weeks on a stable dose) or at doses ≥ 10 mg/day.

a Cockroft's formulae should be applied: in male: creatinine clearance = (140-age) x weight / 72 x creatininemia in female: creatinine clearance = 0.85 x (140-age) x weight / 72 x creatininemia