Two Different Dosages of Nebulized Steroid Versus Parenteral Steroid in the Management of COPD Exacerbations

NCT ID: NCT01865500

Last Updated: 2013-05-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-01-31
• Study Completion Date: 2013-05-31

Brief Summary

Chronic obstructive pulmonary disease (COPD) is a common disease that has a chronic and progressive course. Patients with COPD may have exacerbations one to four times in a year. Numbers of exacerbations are important because of increased morbidity and mortality and healthcare costs.

Systemic corticosteroids (SC) are recommended in the management of exacerbations of COPD as well as bronchodilator, oxygen and antibacterial treatment by all international guidelines. However, there are still some concerns about systemic corticosteroid use because COPD patients are older and relatively immobilized. In addition, exacerbation rate is significantly higher in a group of COPD patients, and these patients need higher amounts of SC in order to control of exacerbation. It results in some adverse effects such as osteoporosis and bone fractures, thinning of the skin, posterior subcapsular cataract formation, glucose intolerance and myopathy. Thus, this condition leads clinicians to seek alternative options. However, there are few studies showing that nebulized steroids (NS) are as effective as SC in exacerbations of COPD and the optimal NS dose is not certain.

The investigators aimed to determine the optimal NS dose and evaluate the efficacy and safety of NS compared with SC in the treatment of patients with COPD exacerbations requiring hospitalization.

Detailed Description

Study Population One hundred twenty patients with moderate or severe COPD exacerbation who are older than 40-years-old, had a smoking history of at least 10-pack-years and requiring hospitalization were included in the study. COPD diagnosis was based on clinical evaluation as defined by the American Thoracic Society (ATS). The patients were excluded if they had a presence of asthma, allergic rhinitis, atopy or any systemic disease (such as diabetes mellitus or hypertension); were exposed to systemic corticosteroids in the preceding month; used more than 1,500 microg/d of inhaled beclomethasone equivalent; were admission to the intensive care unit (pH<7.30 and/or arterial partial pressure of carbon dioxide (PaCO2) > 70 mm Hg, and/or arterial partial pressure of oxygen (PaO2) < 50 mm Hg despite supplemental oxygen); if a specific cause for the exacerbation, such as pneumonia, pneumothorax, or heart failure, was diagnosed.

Study Design The study was as a randomized, double-blind, parallel design trial. The randomization order was determined using a computer-generated list of random numbers. Eligible patients were randomly allocated to one of the three treatment groups, that is, parenteral corticosteroid (PS), 4 mg nebulized budesonide (NB) or 8 mg NB. The efficacy of the study medications was assessed at hospitalization, 24 h, 48 h and before discharge. Patients were monitored during the hospitalization. Patients were withdrawn from the study if they required intubation and managed in intensive care unit.

Treatments Treatment in the PS group consisted of methylprednisolone 40 mg (intravenous ampoule); treatment in the NB groups consisted of nebulized budesonide suspension (Pulmicort nebuampul® 0.5 mg/ml; Astra-Zeneca Pharmaceutical Production) for 10 days. Budesonide were given as 2 mg twice daily or 4 mg twice daily; methylprednisolone were given once daily intravenously.

Nebulization procedures were performed by jet nebulizer (Porta Neb® Ventstream® 1803; Medic-Aid) with 80% of output of less than 5 micron. Patients received standard treatment with a nebulized ß-agonist (salbutamol 3.01 mg) and anticholinergic (ipratropium bromide 0.5 mg) combination every 6 hours, intravenous aminophylline (0.5 mg/kg/h) and oral or intravenous antibacterial at the discretion of the attending physician. Supplementary oxygen therapy was used to maintain oxygen saturation (SaO2) >90%.

Measurements Patients were assessed every 12 h during the acute phase (from H0 to H48), and at hospital discharge. Arterial blood samples were taken at baseline, 24, 48 h and before discharge for the determination of PaO2, PaCO2, and pH, regardless of whether the patient was on room air or on supplementary oxygen. Spirometry (Sensor Medics, Vmax22) was carried out before and 15 to 20 min after bronchodilator nebulization (ß2-agonist and ipratropium bromide) according to ATS standards. Dyspnea was assessed according to the modified Borg scale. Complete blood cell counts were obtained at entry, and blood glucose, sodium, potassium were measured at H0 and H48.

Endpoints The primary endpoint was to assess treatment efficacy by the change of arterial blood gases from H0 to H24, H48 and before discharge. Secondary endpoints included the changes in FEV1 (forced expiratory volume in 1 second), dyspnea score, duration of hospitalization, and occurrence of adverse events. An adverse event was defined as any medical event reported by the attending physician and events resulting in treatment change, discontinuation study medication or prolonged of hospitalization.

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

COPD exacerbation; Nebulized budesonide; Parenteral steroid

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Metil prednisolone & Budesonide 4mg

Group Type: ACTIVE_COMPARATOR

Budesonide 4 mg

Intervention Type: DRUG

It will be evaluated at baseline, 24 h, 48 h and before discharge

Metil prednisolone

Intervention Type: DRUG

Metil prednisolone & Budesonide 8 mg

Group Type: ACTIVE_COMPARATOR

Budesonide 8 mg

Intervention Type: DRUG

Baseline FEV1 and before discharge FEV1 were evaluated

Metil prednisolone

Intervention Type: DRUG

Budesonide 4 mg & Budesonide 8 mg

Group Type: ACTIVE_COMPARATOR

Budesonide 4 mg

Intervention Type: DRUG

It will be evaluated at baseline, 24 h, 48 h and before discharge

Budesonide 8 mg

Intervention Type: DRUG

Baseline FEV1 and before discharge FEV1 were evaluated

Interventions

Budesonide 4 mg

It will be evaluated at baseline, 24 h, 48 h and before discharge

Intervention Type: DRUG

Budesonide 8 mg

Baseline FEV1 and before discharge FEV1 were evaluated

Intervention Type: DRUG

Metil prednisolone

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients with moderate or severe COPD exacerbation who are older than 40-years-old
• A smoking history of at least 10-pack-years
• Requiring hospitalization because of COPD exacerbation

Exclusion Criteria

• Presence of asthma, allergic rhinitis, atopy or any systemic disease (such as diabetes mellitus or hypertension)
• Exposed to systemic corticosteroids in the preceding month or used more than 1,500 microg/d of inhaled beclomethasone equivalent
• Admission to the intensive care unit (pH<7.30 and/or PaCO2 > 70 mm Hg, and/or PaO2 < 50 mm Hg despite supplemental oxygen)
• If a specific cause for the exacerbation, such as pneumonia, pneumothorax, or heart failure, was diagnosed.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ataturk University

OTHER

Sponsor Role: lead

Responsible Party

Elif Yilmazel Ucar

Pulmonary Disease

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Ataturk University Faculty of Medicine Pulmonary Disease Department

Erzurum, , Turkey (Türkiye)

Countries

Turkey (Türkiye)

References

Maltais F, Ostinelli J, Bourbeau J, Tonnel AB, Jacquemet N, Haddon J, Rouleau M, Boukhana M, Martinot JB, Duroux P. Comparison of nebulized budesonide and oral prednisolone with placebo in the treatment of acute exacerbations of chronic obstructive pulmonary disease: a randomized controlled trial. Am J Respir Crit Care Med. 2002 Mar 1;165(5):698-703. doi: 10.1164/ajrccm.165.5.2109093.

Reference Type: BACKGROUND

PMID: 11874817 (View on PubMed)

Gaude GS, Nadagouda S. Nebulized corticosteroids in the management of acute exacerbation of COPD. Lung India. 2010 Oct;27(4):230-5. doi: 10.4103/0970-2113.71957.

Reference Type: BACKGROUND

PMID: 21139721 (View on PubMed)

Gunen H, Mirici A, Meral M, Akgun M. Steroids in acute exacerbations of chronic obstructive pulmonary disease: are nebulized and systemic forms comparable? Curr Opin Pulm Med. 2009 Mar;15(2):133-7. doi: 10.1097/MCP.0b013e32832185da.

Reference Type: RESULT

PMID: 19532028 (View on PubMed)

Other Identifiers

EUcar

Identifier Type: -

Identifier Source: org_study_id