Effect of Salmeterol on Fluid Clearance From Alveolar-Capillary Membrane in COPD Patients

Chronic Obstructive Pulmonary Disease Clinical Trial

— SALM1  

Official title:

Salmeterol Improves Fluid Clearance From Alveolar-Capillary Membrane in COPD Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01271556
• Other study ID #: SALM101012008
• Status: Completed
• Phase: N/A
• First received: January 5, 2011
• Last updated: January 5, 2011
• Start date: December 2008
• Est. completion date: July 2009

Study information

• Verified date: December 2008
• Source: University of Milan
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

The cardiovascular component associated with COPD plays a major role in prognosis of the disease, being responsible of 25% of the deaths. Experimental and initial clinical data suggest that beta-adrenergic agonists accelerate clearance of excess fluid from the alveolar airspace, with potential positive effect on cardiogenic pulmonary edema.

The aim of this study was to investigate the effects of a long-acting beta-2 agonist, salmeterol, on alveolar fluid clearance in COPD patients by evaluating the diffusive and mechanical lung properties. Our experimental model to test alveolar fluid clearance was rapid saline intravenous infusion.

Ten COPD and 10 healthy subjects treated with salmeterol or placebo 4 hours before the begin of the study were evaluated, in four non consecutive days, just before and after a saline infusion or a similar period without infusion.

Both in COPD and healthy subjects rapid saline infusion, with placebo or salmeterol premedication, lead to a significant decrease of DLCO and FEV1. Nonetheless, salmeterol pretreatment lead to a significant reduction of the impairment of gas exchange due to saline infusion (-64% of DLCO reduction in comparison with placebo), whilst it did not affect the changes in FEV1. In the control setting, with no infusion, we did not find any significant change of both DLCO and mechanical properties of the lung.

In conclusions, in COPD patients salmeterol appears to provide a protective effect against an acute alveolar fluid clereance challenge secondary to lung fluid overload providing an intriguing mechanistic explanation for the benefits observed in larger trials.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: July 2009
• Est. primary completion date: March 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 40 Years to 80 Years

Eligibility

Inclusion Criteria:

• COPD diagnosis (consistent with the diagnostic standards of the European Respiratory Society, ERS, for the management of COPD)

• stable condition for =4 weeks and had a prebronchodilator forced expiratory volume in one second (FEV1) of <60% of the predicted value

Exclusion Criteria:

• known allergies to the study medication

• long-term oxygen therapy

• history of asthma, allergic rhinitis, atopy, or a total blood eosinophil count greater than 400/mm3

• chronic heart failure, untreated arterial hypertension, myocardial infarction within the last 6 months, diabetes mellitus

• increased serum potassium levels.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Bronchodilator Agents
• Chronic Obstructive Pulmonary Disease
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive
• Salmeterol
• Salmeterol Effect Against an Acute Alveolar Fluid Clearance Challenge Secondary to Lung Fluid Overload in COPD Patients

Intervention

Drug:
• Salmeterol
50 mcg MDI (inhalatory), once on days A and C at t=0,

Procedure:
• saline infusion (0.9 per cent sodium chloride)
rapid 50-minute 750-ml 0.9% saline infusion 240 minutes after inhalatory treatment on day A and B

Other:
• Placebo
placebo, inhalatory (MDI) once

Locations

Country	Name	City	State
Italy	Respiratory Medicine Section, Dipartimento Toraco-Polmonare e Cardiocircolatorio, Università degli Studi di Milano, San Paolo Hospital	Milan

Sponsors (1)

Lead Sponsor	Collaborator
University of Milan

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	change caused by the effect of salmeterol on lung diffusion capacity for carbon monoxide (DLCO) and its components after a challenge with rapid intravenous saline infusion	DLCO was measured twice (Sensor Medics 2200 Pulmonary Functional Test System, USA) for each oxygen mixture, with washout intervals of at least 4 minutes (the average was taken as the final result), according to the European Respiratory Society guidelines. The single-breath alveolar volume (VA) was derived by methane dilution. Alveolar-capillary membrane diffusing capacity (DM) and capillary blood volume available for gas exchange (Vc) were determined with the same equipment, according to the classic Roughton and Forster method	240 and 290 minutes after inhalatory treatment pulmonary function tests were performed	No
Secondary	changes in mechanical lung properties	Mouth flow was measured by a mass flowmeter, and volume was obtained by numerical integration of the flow signal. Spirometry and flow-volume curves were obtained by manoeuvres consisting of six to eight regular tidal breaths, a forced expiration initiated from end-tidal inspiration to residual volume (partial expiratory flow-volume curve, PEFV), followed by a fast inspiration to total lung capacity and a forced expiration to residual volume (maximal expiratory flow-volume curve, MEFV).	240 and 290 minutes after inhalatory treatment	No