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

NCT01271556 | Completed

• 1 other identifier: SALM101012008
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Keywords

COPD; LABA; salmeterol

Outcome Measures

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

  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

Secondary Outcomes (1)

• changes in mechanical lung properties

  240 and 290 minutes after inhalatory treatment

Study Arms (4)

1, salmeterol, saline infusion

EXPERIMENTAL

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; Procedure: saline infusion (0.9 per cent sodium chloride)

2, placebo, saline infusion

PLACEBO COMPARATOR

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); Other: Placebo

3, salmeterol, no saline infusion

ACTIVE COMPARATOR

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

4, placebo, no saline infusion

PLACEBO COMPARATOR

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

Interventions

Salmeterol DRUG

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

Also known as: long acting bronchodilator agents

1, salmeterol, saline infusion; 3, salmeterol, no saline infusion

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

Also known as: physiologic saline solution

1, salmeterol, saline infusion; 2, placebo, saline infusion

Placebo OTHER

placebo, inhalatory (MDI) once

2, placebo, saline infusion; 4, placebo, no saline infusion

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Milan: lead

Study Sites (1)

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

Milan, Milan, 20142, Italy

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Salmeterol Xinafoate

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Albuterol; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines

Study Officials

• Stefano Centanni, MD

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

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: January 5, 2011
• First Posted: January 6, 2011
• Study Start: December 1, 2008
• Primary Completion: March 1, 2009
• Study Completion: July 1, 2009
• Last Updated: January 6, 2011

Record last verified: 2008-12

Locations

IT (1)