Combined salmeterol and fluticasone in the treatment of chronic obstructive pulmonary disease: A randomised controlled trial

TRISTAN Study Group

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Background: Inhaled longacting β2 agonists improve lung function and health status in symptomatic chronic obstructive pulmonary disease (COPD), whereas inhaled corticosteroids reduce the frequency of acute episodes of symptom exacerbation and delay deterioration in health status. We postulated that a combination of these treatments would be better than each component used alone.Methods: 1465 patients with COPD were recruited from outpatient departments in 25 countries. They were treated in a randomised, double-blind, parallel-group, placebo-controlled study with either 50 μg salmeterol twice daily (n=372), 500 μg fluticasone twice daily (n=374), 50 μg salmeterol and 500 μg fluticasone twice daily (n=358), or placebo (n=361) for 12 months. The primary outcome was the pretreatment forced expiratory volume in 1 s (FEV1) after 12 months treatment' and after patients had abstained from all bronchodilators for at least 6 h and from study medication for at least 12 h. Secondary outcomes were other lung function measurements, symptoms and rescue treatment use, the number of exacerbations, patient withdrawals, and disease-specific health status. We assessed adverse events, serum cortisol concentrations, skin bruising, and electrocardiograms. Analysis was as predefined in the study protocol.Findings: All active treatments improved lung function, symptoms, and health status and reduced use of rescue medication and frequency of exacerbations. Combination therapy improved pretreatment FEV1 significantly more than did placebo (treatment difference 133 mL, 95% CI 105–161, p<0·0001), salmeterol (73 mL, 46–101, p<0·0001), or fluticasone alone (95 mL, 67–122, p<0·0001). Combination treatment produced a clinically significant improvement in health status and the greatest reduction in daily symptoms. All treatments were well tolerated with no difference in the frequency of adverse events, bruising, or clinically significant falls in serum cortisol concentration.Interpretation: Because inhaled long-acting β2 agonists and corticosteroid combination treatment produces better control of symptoms and lung function, with no greater risk of side-effects than that with use of either component alone, this combination treatment should be considered for patients with COPD.
OriginalsprogEngelsk
TidsskriftLancet
Vol/bind361
Udgave nummer9356
Sider (fra-til)449-456
Antal sider8
ISSN0140-6736
DOI
StatusUdgivet - 8. feb. 2003
Udgivet eksterntJa

Fingeraftryk

Chronic Obstructive Pulmonary Disease
Randomized Controlled Trials
Lung
Placebos
Forced Expiratory Volume
Adrenal Cortex Hormones
Salmeterol Xinafoate Drug Combination Fluticasone Propionate
Serum
Electrocardiography
Outpatients
Skin

Emneord

  • administration & dosage: Adrenergic beta-Agonists
  • Aged
  • administration & dosage: Albuterol
  • administration & dosage: Androstadienes
  • administration & dosage: Anti-Inflammatory Agents, Steroidal
  • Comparative Study
  • chemically induced: Contusions
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • drug effects: Forced Expiratory Volume
  • Human
  • blood: Hydrocortisone
  • Male
  • Middle Age
  • diagnosis: Pulmonary Disease, Chronic Obstructive
  • etiology: Substance Withdrawal Syndrome
  • Support, Non-U.S. Gov't

Citer dette

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title = "Combined salmeterol and fluticasone in the treatment of chronic obstructive pulmonary disease: A randomised controlled trial",
abstract = "Background: Inhaled longacting β2 agonists improve lung function and health status in symptomatic chronic obstructive pulmonary disease (COPD), whereas inhaled corticosteroids reduce the frequency of acute episodes of symptom exacerbation and delay deterioration in health status. We postulated that a combination of these treatments would be better than each component used alone.Methods: 1465 patients with COPD were recruited from outpatient departments in 25 countries. They were treated in a randomised, double-blind, parallel-group, placebo-controlled study with either 50 μg salmeterol twice daily (n=372), 500 μg fluticasone twice daily (n=374), 50 μg salmeterol and 500 μg fluticasone twice daily (n=358), or placebo (n=361) for 12 months. The primary outcome was the pretreatment forced expiratory volume in 1 s (FEV1) after 12 months treatment' and after patients had abstained from all bronchodilators for at least 6 h and from study medication for at least 12 h. Secondary outcomes were other lung function measurements, symptoms and rescue treatment use, the number of exacerbations, patient withdrawals, and disease-specific health status. We assessed adverse events, serum cortisol concentrations, skin bruising, and electrocardiograms. Analysis was as predefined in the study protocol.Findings: All active treatments improved lung function, symptoms, and health status and reduced use of rescue medication and frequency of exacerbations. Combination therapy improved pretreatment FEV1 significantly more than did placebo (treatment difference 133 mL, 95{\%} CI 105–161, p<0·0001), salmeterol (73 mL, 46–101, p<0·0001), or fluticasone alone (95 mL, 67–122, p<0·0001). Combination treatment produced a clinically significant improvement in health status and the greatest reduction in daily symptoms. All treatments were well tolerated with no difference in the frequency of adverse events, bruising, or clinically significant falls in serum cortisol concentration.Interpretation: Because inhaled long-acting β2 agonists and corticosteroid combination treatment produces better control of symptoms and lung function, with no greater risk of side-effects than that with use of either component alone, this combination treatment should be considered for patients with COPD.",
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author = "Peter Calverley and Romain Pauwels and J{\o}rgen Vestbo and Paul Jones and Neil Pride and Amund Gulsvik and Julie Anderson and Claire Maden and {TRISTAN Study Group}",
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language = "English",
volume = "361",
pages = "449--456",
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Combined salmeterol and fluticasone in the treatment of chronic obstructive pulmonary disease: A randomised controlled trial. / TRISTAN Study Group.

I: Lancet, Bind 361, Nr. 9356, 08.02.2003, s. 449-456.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Combined salmeterol and fluticasone in the treatment of chronic obstructive pulmonary disease: A randomised controlled trial

AU - Calverley, Peter

AU - Pauwels, Romain

AU - Vestbo, Jørgen

AU - Jones, Paul

AU - Pride, Neil

AU - Gulsvik, Amund

AU - Anderson, Julie

AU - Maden, Claire

AU - TRISTAN Study Group

PY - 2003/2/8

Y1 - 2003/2/8

N2 - Background: Inhaled longacting β2 agonists improve lung function and health status in symptomatic chronic obstructive pulmonary disease (COPD), whereas inhaled corticosteroids reduce the frequency of acute episodes of symptom exacerbation and delay deterioration in health status. We postulated that a combination of these treatments would be better than each component used alone.Methods: 1465 patients with COPD were recruited from outpatient departments in 25 countries. They were treated in a randomised, double-blind, parallel-group, placebo-controlled study with either 50 μg salmeterol twice daily (n=372), 500 μg fluticasone twice daily (n=374), 50 μg salmeterol and 500 μg fluticasone twice daily (n=358), or placebo (n=361) for 12 months. The primary outcome was the pretreatment forced expiratory volume in 1 s (FEV1) after 12 months treatment' and after patients had abstained from all bronchodilators for at least 6 h and from study medication for at least 12 h. Secondary outcomes were other lung function measurements, symptoms and rescue treatment use, the number of exacerbations, patient withdrawals, and disease-specific health status. We assessed adverse events, serum cortisol concentrations, skin bruising, and electrocardiograms. Analysis was as predefined in the study protocol.Findings: All active treatments improved lung function, symptoms, and health status and reduced use of rescue medication and frequency of exacerbations. Combination therapy improved pretreatment FEV1 significantly more than did placebo (treatment difference 133 mL, 95% CI 105–161, p<0·0001), salmeterol (73 mL, 46–101, p<0·0001), or fluticasone alone (95 mL, 67–122, p<0·0001). Combination treatment produced a clinically significant improvement in health status and the greatest reduction in daily symptoms. All treatments were well tolerated with no difference in the frequency of adverse events, bruising, or clinically significant falls in serum cortisol concentration.Interpretation: Because inhaled long-acting β2 agonists and corticosteroid combination treatment produces better control of symptoms and lung function, with no greater risk of side-effects than that with use of either component alone, this combination treatment should be considered for patients with COPD.

AB - Background: Inhaled longacting β2 agonists improve lung function and health status in symptomatic chronic obstructive pulmonary disease (COPD), whereas inhaled corticosteroids reduce the frequency of acute episodes of symptom exacerbation and delay deterioration in health status. We postulated that a combination of these treatments would be better than each component used alone.Methods: 1465 patients with COPD were recruited from outpatient departments in 25 countries. They were treated in a randomised, double-blind, parallel-group, placebo-controlled study with either 50 μg salmeterol twice daily (n=372), 500 μg fluticasone twice daily (n=374), 50 μg salmeterol and 500 μg fluticasone twice daily (n=358), or placebo (n=361) for 12 months. The primary outcome was the pretreatment forced expiratory volume in 1 s (FEV1) after 12 months treatment' and after patients had abstained from all bronchodilators for at least 6 h and from study medication for at least 12 h. Secondary outcomes were other lung function measurements, symptoms and rescue treatment use, the number of exacerbations, patient withdrawals, and disease-specific health status. We assessed adverse events, serum cortisol concentrations, skin bruising, and electrocardiograms. Analysis was as predefined in the study protocol.Findings: All active treatments improved lung function, symptoms, and health status and reduced use of rescue medication and frequency of exacerbations. Combination therapy improved pretreatment FEV1 significantly more than did placebo (treatment difference 133 mL, 95% CI 105–161, p<0·0001), salmeterol (73 mL, 46–101, p<0·0001), or fluticasone alone (95 mL, 67–122, p<0·0001). Combination treatment produced a clinically significant improvement in health status and the greatest reduction in daily symptoms. All treatments were well tolerated with no difference in the frequency of adverse events, bruising, or clinically significant falls in serum cortisol concentration.Interpretation: Because inhaled long-acting β2 agonists and corticosteroid combination treatment produces better control of symptoms and lung function, with no greater risk of side-effects than that with use of either component alone, this combination treatment should be considered for patients with COPD.

KW - administration & dosage: Adrenergic beta-Agonists

KW - Aged

KW - administration & dosage: Albuterol

KW - administration & dosage: Androstadienes

KW - administration & dosage: Anti-Inflammatory Agents, Steroidal

KW - Comparative Study

KW - chemically induced: Contusions

KW - Double-Blind Method

KW - Drug Administration Schedule

KW - Drug Therapy, Combination

KW - Female

KW - Follow-Up Studies

KW - drug effects: Forced Expiratory Volume

KW - Human

KW - blood: Hydrocortisone

KW - Male

KW - Middle Age

KW - diagnosis: Pulmonary Disease, Chronic Obstructive

KW - etiology: Substance Withdrawal Syndrome

KW - Support, Non-U.S. Gov't

U2 - 10.1016/S0140-6736(03)12459-2

DO - 10.1016/S0140-6736(03)12459-2

M3 - Journal article

VL - 361

SP - 449

EP - 456

JO - Lancet

JF - Lancet

SN - 0140-6736

IS - 9356

ER -