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NCT Number: NCT01271556

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

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.

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Key information

Age range

40 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Respiratory Medicine Section, Dipartimento Toraco-Polmonare e Cardiocircolatorio, Università degli Studi di Milano, San Paolo Hospital

Milan, 20142, Italy

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Salmeterol

Drug

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

Other names: long acting bronchodilator agents

saline infusion (0.9 per cent sodium chloride)

Procedure

rapid 50-minute 750-ml 0.9% saline infusion 240 minutes after inhalatory treatment on day A and B

Other names: physiologic saline solution

Placebo

Other

placebo, inhalatory (MDI) once

Primary outcomes

  1. 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

    Time frame: 240 and 290 minutes after inhalatory treatment pulmonary function tests were performed

    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

Secondary outcomes

  1. changes in mechanical lung properties

    Time frame: 240 and 290 minutes after inhalatory treatment

    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).

Sponsors and collaborators

Lead sponsor

University of Milan

Other

Registry information

Official study title

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

Acronym: SALM1

Important dates

Study start
2008
Primary completion
2009
Study completion
2009
First posted
Jan 6, 2011
Registry last updated
Jan 6, 2011

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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