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

NCT ID: NCT01271556

Last Updated: 2011-01-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-12-31
• Study Completion Date: 2009-07-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

Salmeterol

Intervention Type: DRUG

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

saline infusion (0.9 per cent sodium chloride)

Intervention Type: PROCEDURE

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

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.

Group Type: PLACEBO_COMPARATOR

saline infusion (0.9 per cent sodium chloride)

Intervention Type: PROCEDURE

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

Placebo

Intervention Type: OTHER

placebo, inhalatory (MDI) once

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.

Group Type: ACTIVE_COMPARATOR

Salmeterol

Intervention Type: DRUG

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

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

placebo, inhalatory (MDI) once

Interventions

Salmeterol

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

Intervention Type: DRUG

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

Intervention Type: PROCEDURE

Placebo

placebo, inhalatory (MDI) once

Intervention Type: OTHER

Other Intervention Names

long acting bronchodilator agents; physiologic saline solution

Eligibility 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.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Milan

OTHER

Sponsor Role: lead

Responsible Party

Respiratory Unit, San Paolo Hospital, University of Milan, Milan, Italy

Principal Investigators

Stefano Centanni, MD

Role: STUDY_DIRECTOR

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

Locations

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

Milan, Milan, Italy

Countries

Italy

Other Identifiers

SALM101012008

Identifier Type: -

Identifier Source: org_study_id