Evaluation Of The Efficacy Of Corticosteroids In Patients With An Acute Exacerbation Of Chronic Obstructive Pulmonary Disease Receiving Ventilator Support

Clinical practice guidelines for the management of chronic obstructive pulmonary disease (COPD) recommend treatment with systemic corticosteroids during acute exacerbations. The results of a Cochrane systematic review show that treatment with systemic corticosteroids improves lung function over the first 72 hours of an exacerbation of COPD but the effect on other outcomes, particularly length of hospital stay, is unclear, so further research should be directed at determining the risk-benefit ratio, particularly those at high risk of developing adverse drug reactions. In critically ill patients, corticosteroid treatment is a risk factor of infections, hyperglucemia and critical-illness neuromuscular abnormalities, and these conditions are associated with an increased morbidity and mortality. The effect of treatment with systemic corticosteroids in COPD patients with acute exacerbation requiring mechanical ventilation has not been evaluated investigated so it is unknown if the corticosteroids could reduce the duration of mechanical ventilation and the length of intensive care unit (ICU) stay or if, on the contrary, the development of adverse events could lead to a longer time on mechanical ventilation and ICU stay.

PRIMARY OBJECTIVES: To evaluate the effect of corticosteroids on the duration of mechanical ventilation, the length of ICU stay, the need for tracheal intubation in patients treated with non-invasive mechanical ventilation. To evaluate the frequency of adverse events: secondary infections, pneumonia, arterial hypertension, hyperglucemia, gastrointestinal bleeding, and critical-illness neuromuscular abnormalities. DESING: Multicenter, prospective, randomized, double blind, placebo-controlled clinical trial.The treatment group will receive intravenous methylprednisolone for 10 days and the control group will receive isotonic saline solution.

Study Overview

• Status: Terminated
• Conditions: COPD
• Intervention / Treatment: Drug: intravenous methylprednisolone; Other: intravenous normal saline solution

• Study Type: Interventional
• Enrollment (Actual): 83
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Madrid
    • Getafe, Madrid, Spain, 28905
      • Hospital Universitario de Getafe

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients (age > 18 years) admitted to participating ICUs with:

  1. Primary diagnosis of COPD exacerbation defined as the presence of two or more of the following clinical features: worsening dyspnea, increase in sputum purulence, increase in sputum volume
  2. respiratory failure [pH < 7,35 with a PaCO2 > 45 mm Hg and respiratory rate more than 23 breaths per minute] requiring mechanical ventilation, invasive or non-invasive mechanical ventilation.

Exclusion Criteria:

1. Primary diagnosis of asthma exacerbation.
2. History of asthma or atopy.
3. Use of systemic corticosteroids within the preceding month.
4. Use of systemic corticosteroids for the treatment of COPD exacerbation at the time of ICU admission for more than 24 hours.
5. Clinical or radiological evidence of pneumonia.
6. Uncontrolled left-ventricular failure (patients with evidence of severe heart failure requiring inotropes or vasoactive drugs).
7. Uncontrolled hypertension arterial (systolic pressure > 180 mm Hg or diastolic pressure > 90 mm Hg despite antihypertensive therapy).
8. Uncontrolled diabetes mellitus.
9. Presence of a neuromuscular disease.
10. History of allergy and or adverse reaction to corticosteroids.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: methylprednisolone	Drug: intravenous methylprednisolone; methylprednisolone 0,5 mg/kg every 6 hours for 72 hours, 0,5 mg/kg every 12 hours on days 4 through 6, 0,5 mg/kg daily for day 7 through day 10
PLACEBO_COMPARATOR: normal saline solution	Other: intravenous normal saline solution; 50 ml of intravenous normal saline solution every 6 hours for 72 hours, 50 ml every 12 hours on days through 6, 50 ml daily for day 7 through day 10.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of mechanical ventilation	Time elapsed between tracheal intubation and extubation (in the group of patients treated with invasive mechanical ventilation),or time elapsed between initiation of non-invasive mechanical ventilation and withdrawal of non-invasive mechanical ventilation (in the group of patients successfully treated with non-invasive mechanical ventilation, or time elapsed between initiation of non-invasive ventilation and extubation (in the case of those patients who failed non-invasiev ventilation and required tracheal intubation).	Participants are followed until ICU discharge
Need for intubation in patients treated with non-invasive mechanical ventilation	Number of patients intubated in the following 48 hours after the initiation of non-invasive mechanical ventilation	Participants are followed until ICU discharge
Length of ICU stay	Time elapsed between ICU admission and ICU discharge (dead or alive)	Participants are followed until ICU discharge

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ICU mortality	Number of participants who die in the ICU	Participants are followed until ICU discharge
Length of hospital stay	Time elapsed between hospital admission and hospital discharge	Participants are followed until hospital discharge

Collaborators and Investigators

• Sponsor: Hospital Universitario Getafe
• Collaborators: GRANT IP041233 FROM FONDO DE INVESTIGACION SANITARIA

Publications and helpful links

General Publications

• Alia I, de la Cal MA, Esteban A, Abella A, Ferrer R, Molina FJ, Torres A, Gordo F, Elizalde JJ, de Pablo R, Huete A, Anzueto A. Efficacy of corticosteroid therapy in patients with an acute exacerbation of chronic obstructive pulmonary disease receiving ventilatory support. Arch Intern Med. 2011 Nov 28;171(21):1939-46. doi: 10.1001/archinternmed.2011.530.

Study record dates

Study Major Dates

• Study Start: July 1, 2005
• Primary Completion (ACTUAL): July 1, 2009
• Study Completion (ACTUAL): July 1, 2009

Study Registration Dates

• First Submitted: January 20, 2011
• First Submitted That Met QC Criteria: January 21, 2011
• First Posted (ESTIMATE): January 24, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): January 24, 2011
• Last Update Submitted That Met QC Criteria: January 21, 2011
• Last Verified: May 1, 2005

More Information

Terms related to this study

• Keywords: acute exacerbation of COPD
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate
• Other Study ID Numbers: CORTICOSTEROIDS AND ACUTE COPD