Salmeterol Effect Against an Acute Alveolar Fluid Clearance Challenge Secondary to Lung Fluid Overload in COPD PatientsSALM1NCT01271556
Effect of Salmeterol on Fluid Clearance From Alveolar-Capillary Membrane in COPD Patients
A study testing Salmeterol and saline infusion (0.9 per cent sodium chloride) in people with Salmeterol Effect Against an Acute Alveolar Fluid Clearance Challenge Secondary to Lung Fluid Overload in COPD Patients and Chronic Obstructive Pulmonary Disease, run by University of Milan at 1 site in Italy.
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… Read more about this study
- Who is it for?
- Ages 40 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Salmeterol Effect Against an Acute Alveolar Fluid Clearance Challenge Secondary to Lung Fluid Overload in COPD Patients, Chronic Obstructive Pulmonary Disease, Bronchodilator Agents
- What is being tested?
- Salmeterol and saline infusion (0.9 per cent sodium chloride)
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteItaly
- Study dates
- Dec 2008to Jul 2009
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Italy1 site
Respiratory Medicine Section, Dipartimento Toraco-Polmonare e Cardiocircolatorio, Università degli Studi di Milano, San Paolo Hospital
Milan, Milan, 20142
About this study
Official title: Salmeterol Improves 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.
Read more
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
- Being tested
- Salmeterol, saline infusion (0.9 per cent sodium chloride), Placebo
- Keywords
- COPD, LABA, salmeterol
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SalmeterolDrug
Also called long acting bronchodilator agents
50 mcg MDI (inhalatory), once on days A and C at t=0,
saline infusion (0.9 per cent sodium chloride)Procedure or surgery
Also called physiologic saline solution
rapid 50-minute 750-ml 0.9% saline infusion 240 minutes after inhalatory treatment on day A and B
PlaceboOther
placebo, inhalatory (MDI) once
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 240 and 290 minutes after inhalatory treatment pulmonary function tests were performed
Secondary outcomes (1)
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).
Measured: 240 and 290 minutes after inhalatory treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jan 2011 (estimated)
- Study startDec 2008
- Primary completionMar 2009
- Study completionJul 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Salmeterol Effect Against an Acute Alveolar Fluid Clearance Challenge Secondary to Lung Fluid Overload in COPD PatientsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Milan
- Sponsor type
- University, hospital or other
- Investigators
- Stefano Centanni, MD, Study director, Respiratory Medicine Section, Dipartimento Toraco-Polmonare e Cardiocircolatorio, Università degli Studi di Milano, San Paolo Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01271556
- Sponsor's protocol ID
- SALM101012008
- Acronym
- SALM1
- Status last verified
- Dec 2008
- First submitted
- 5 Jan 2011
- Last updated
- 6 Jan 2011
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Jan 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Salmeterol Improves Fluid Clearance From Alveolar-Capillary Membrane in COPD Patients
- ClinicalTrials.gov ID
- NCT01271556
- Acronym / sponsor ID
- SALM1 / SALM101012008
- 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
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University of MilanUniversity, hospital or other
- Study start
- Dec 2008
- Primary completion
- Mar 2009 (actual)
- Study completion
- Jul 2009 (actual)
- First posted
- 6 Jan 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 1, salmeterol, saline infusion | Experimental | Drug: Salmeterol, Procedure: saline infusion (0.9 per cent sodium chloride)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. |
| 2, placebo, saline infusion | Placebo comparator | Procedure: saline infusion (0.9 per cent sodium chloride), Other: PlaceboIn 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. |
| 3, salmeterol, no saline infusion | Active comparator | Drug: SalmeterolIn 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. |
| 4, placebo, no saline infusion | Placebo comparator | Other: PlaceboIn 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. |
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SalmeterolAlso: long acting bronchodilator agents50 mcg MDI (inhalatory), once on days A and C at t=0, | Drug | 1, salmeterol, saline infusion, 3, salmeterol, no saline infusion |
| saline infusion (0.9 per cent sodium chloride)Also: physiologic saline solutionrapid 50-minute 750-ml 0.9% saline infusion 240 minutes after inhalatory treatment on day A and B | Procedure or surgery | 1, salmeterol, saline infusion, 2, placebo, saline infusion |
| Placeboplacebo, inhalatory (MDI) once | Other | 2, placebo, saline infusion, 4, placebo, no saline infusion |
Primary outcome
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
1 secondary outcome
changes in mechanical lung properties
Time frame: 240 and 290 minutes after inhalatory treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jan 2011.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stefano Centanni, MD study director
Respiratory Medicine Section, Dipartimento Toraco-Polmonare e Cardiocircolatorio, Università degli Studi di Milano, San Paolo Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Salmeterol and saline infusion (0.9 per cent sodium chloride) in people with Salmeterol Effect Against an Acute Alveolar Fluid Clearance Challenge Secondary to Lung Fluid Overload in COPD Patients and Chronic Obstructive Pulmonary Disease, run by University of Milan at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Jan 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jan 2011.