Effect of Salmeterol on Fluid Clearance From Alveolar-Capillary Membrane in COPD Patients (SALM1)

This study has been completed.
Sponsor:
Information provided by:
University of Milan
ClinicalTrials.gov Identifier:
NCT01271556
First received: January 5, 2011
Last updated: NA
Last verified: December 2008
History: No changes posted
  Purpose

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.


Condition Intervention
Salmeterol Effect Against an Acute Alveolar Fluid Clearance Challenge Secondary to Lung Fluid Overload in COPD Patients
Chronic Obstructive Pulmonary Disease
Bronchodilator Agents
Salmeterol
Drug: Salmeterol
Procedure: saline infusion (0.9 per cent sodium chloride)
Other: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Official Title: Salmeterol Improves Fluid Clearance From Alveolar-Capillary Membrane in COPD Patients

Resource links provided by NLM:


Further study details as provided by University of Milan:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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 Outcome Measures:
  • changes in mechanical lung properties [ Time Frame: 240 and 290 minutes after inhalatory treatment ] [ Designated as safety issue: No ]
    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).


Enrollment: 20
Study Start Date: December 2008
Study Completion Date: July 2009
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1, salmeterol, saline infusion
In 10 COPD patients and 10 healthy subjects, tiotropium and long-acting and short-acting beta-2 agonists were withdrawn at least 72 hours if assumed, 24 hours, and 12 hours, respectively, prior to each test day. Salmeterol 50 mcg on days A was administered between 8 AM and 10 AM. Patients and healthy subjects underwent a rapid 50-minute 750-ml 0.9% saline infusion 240 minutes after inhalatory treatment (salmeterol 50 mcg MDI), and mixed venous blood was withdrawn for measurements of hematocrit (Htc), Hb, and albumin concentration 10 minutes before and 10 minutes after the infusion. 240 and 290 minutes after inhalatory treatment, pulmonary function tests were performed.
Drug: Salmeterol
50 mcg MDI (inhalatory), once on days A and C at t=0,
Other Name: long acting bronchodilator agents
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 Name: physiologic saline solution
Placebo Comparator: 2, placebo, saline infusion
In 10 COPD patients and 10 healthy subjects, tiotropium and long-acting and short-acting beta-2 agonists were withdrawn at least 72 hours if assumed, 24 hours, and 12 hours, respectively, prior to test day. Placebo was administered between 8 AM and 10 AM. Patients and healthy subjects underwent a rapid 50-minute 750-ml 0.9% saline infusion 240 minutes after inhalatory treatment (placeboI), and mixed venous blood was withdrawn for measurements of hematocrit (Htc), Hb, and albumin concentration 10 minutes before and 10 minutes after the infusion. 240 and 290 minutes after inhalatory treatment, pulmonary function tests were performed.
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 Name: physiologic saline solution
Other: Placebo
placebo, inhalatory (MDI) once
Active Comparator: 3, salmeterol, no saline infusion
In 10 COPD patients and 10 healthy subjects, tiotropium and long-acting and short-acting beta-2 agonists were withdrawn at least 72 hours if assumed, 24 hours, and 12 hours, respectively, prior to test day. Salmeterol 50 mcg on days A was administered between 8 AM and 10 AM. 240 and 290 minutes after inhalatory treatment, pulmonary function tests were performed.
Drug: Salmeterol
50 mcg MDI (inhalatory), once on days A and C at t=0,
Other Name: long acting bronchodilator agents
Placebo Comparator: 4, placebo, no saline infusion
In 10 COPD patients and 10 healthy subjects, tiotropium and long-acting and short-acting beta-2 agonists were withdrawn at least 72 hours if assumed, 24 hours, and 12 hours, respectively, prior to test day. Placebo was administered between 8 AM and 10 AM. 240 and 290 minutes after inhalatory treatment (placebo), pulmonary function tests were performed.
Other: Placebo
placebo, inhalatory (MDI) once

  Eligibility

Ages Eligible for Study:   40 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01271556

Locations
Italy
Respiratory Medicine Section, Dipartimento Toraco-Polmonare e Cardiocircolatorio, Università degli Studi di Milano, San Paolo Hospital
Milan, Italy, 20142
Sponsors and Collaborators
University of Milan
Investigators
Study Director: Stefano Centanni, MD Respiratory Medicine Section, Dipartimento Toraco-Polmonare e Cardiocircolatorio, Università degli Studi di Milano, San Paolo Hospital
  More Information

No publications provided

Responsible Party: Dr. Fabiano Di Marco, Respiratory Unit, San Paolo Hospital, University of Milan, Milan, Italy
ClinicalTrials.gov Identifier: NCT01271556     History of Changes
Other Study ID Numbers: SALM101012008
Study First Received: January 5, 2011
Last Updated: January 5, 2011
Health Authority: Italy: Ethics Committee

Keywords provided by University of Milan:
COPD
LABA
salmeterol

Additional relevant MeSH terms:
Lung Diseases
Respiration Disorders
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Respiratory Tract Diseases
Bronchodilator Agents
Salmeterol
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 17, 2014