Try the modernized beta website. Learn more about the modernization effort.
Working… Menu

Extended Steroid in Use in Community Acquired Pneumonia (CAP)(e) (ESCAPe)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01283009
Recruitment Status : Completed
First Posted : January 25, 2011
Results First Posted : October 8, 2020
Last Update Posted : October 8, 2020
Information provided by (Responsible Party):
VA Office of Research and Development

Brief Summary:

The goal of the study is to determine whether providing early treatment with a glucocorticoid drug, called methylprednisolone, will improve survival in critically ill patients with severe community-acquired pneumonia (CAP). Pneumonia develops when bacteria and other agents invade the lungs. The body's immune system creates a response to produce inflammation to kill the bacteria. A moderate amount of inflammation is beneficial. But, in patients sick enough to be admitted to the ICU, inflammation is frequently out of control. When the body cannot regulate inflammation vital organs (brain, heart, lung, kidney, liver) may be damaged, contributing to death or residual organ damage for those who survive. Glucocorticoids help reduce inflammation. Recent studies have shown that when the body is unable to produce sufficient amounts of glucocorticoids, inflammation can get out of control. Under these circumstances, glucocorticoids given in small doses may help aid the body's ability to reduce inflammation and improve recovery. In a small preliminary trial, glucocorticoid treatment, in addition to standard antibiotic treatment, sped up recovery from pneumonia. It also decreased the length of hospital stay, and increased survival. This Cooperative Studies Program (CSP) study will be the first large-scale, prospective, randomized clinical trial evaluating whether or not this treatment improves recovery.

In this study, at each site, patients with severe CAP will be assigned to one of two treatment groups. One group will receive methylprednisolone and the other will receive a placebo (an inert substance that will look like the drug). The investigators have chosen a total duration of treatment of 20 days (7 days full dose followed by slow reduction over 13 days) to prevent relapse of inflammation and allow the body to recover its own ability to produce glucocorticoid. All patients will also receive standardized management of CAP in accordance with current practice guidelines. The study will take into consideration when assigning the treatment each participating site, and whether or not the patient requires mechanical ventilation at the time of assignment. Patients will be followed clinically for 180 days. The primary outcome is all cause 60-day mortality. Secondary outcomes are (1) in-hospital morbidity-mortality, including ventilator-free days, multiorgan dysfunction syndrome (MODS)-free days, duration of ICU and hospital stay, and hospital discharge; and (2) posthospital discharge morbidity-mortality, including cardiovascular complications, functional and general health status in the first 180 days, rehospitalization, and mortality at 1 year. Serial blood samples will also be collected and stored for future translational research relating longitudinal inflammation markers to clinical outcomes.

This study will advance knowledge on the relationship between inflammation and long-term outcome in severe CAP.

Condition or disease Intervention/treatment Phase
Community Acquired Respiratory Disease Syndrome Drug: Inactive Substance Drug: Methylprednisolone Phase 3

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 584 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: CSP #574 - Evaluate the Safety and Efficacy of Methylprednisolone in Hospitalized Veterans With Severe Community-Acquired Pneumonia
Actual Study Start Date : January 9, 2012
Actual Primary Completion Date : July 31, 2016
Actual Study Completion Date : August 31, 2016

Arm Intervention/treatment
Placebo Comparator: Arm 1: Inactive substance
Inactive substance
Drug: Inactive Substance
Inactive Substance will be given in a double-blind fashion for 20 full days. The treatment course includes a bolus dose on the day of randomization, 7 days of full dose (40 mg/day), 7 days of half dose (20 mg/day), and 6 days of tapering doses (12 mg/day and 4 mg/day).

Active Comparator: Arm 2: Methylprednisolone
Drug: Methylprednisolone
Methylprednisolone will be given in a double-blind fashion for 20 full days. The treatment course includes a bolus dose on the day of randomization, 7 days of full dose (40 mg/day), 7 days of half dose (20 mg/day), and 6 days of tapering doses (12 mg/day and 4 mg/day).
Other Name: Medrol

Primary Outcome Measures :
  1. 60-day Mortality [ Time Frame: 60-day ]
    The primary outcome is all-cause mortality at 60 days, defined by whether the patient has died by the end of study day 60.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patient's origin. Patients are classified as having Community Acquired Pneumonia (CAP) if they are admitted directly from outside the hospital, including private residence, nursing home, rehabilitation center, other long-term care facility (health care-associated pneumonia (HCAP)).
  • Clinical diagnosis of CAP.
  • Have radiographically confirmed pneumonia (new or progressive pulmonary infiltrate(s) on chest radiograph or chest computed tomography scan consistent with bacterial pneumonia) AND have acute illness ( <=7 days' duration) with at least three of the following clinical signs or symptoms consistent with a lower respiratory tract infection:

New or increased cough Purulent sputum or change in sputum character Auscultatory findings consistent with pneumonia (e.g., rales, egophony, findings of consolidation) Dyspnea, tachypnea, or hypoxemia (O2 saturation <90% on room air or PaO2 <60 mmHg) Fever >= 38 C oral (>=38.5 C rectally or tympanically) or hypothermia (<=36 C) White blood cell count greater than 10,000 cells/mm3 or less than 4,000 cells/mm3 Greater than 15% immature neutrophils (bands) irrespective of WBC count

  • Diagnosis of severe CAP. Pneumonia of sufficient severity to require admission to the ICU (including intermediate care unit) and meeting >=1 major or >= 3 minor modified Infectious Diseases Society of America (IDSA)/American

Thoracic Society (ATS) criteria.:

  • 1 Major Criteria

    1. Use of invasive or noninvasive mechanical ventilation
    2. Vasopressors for shock despite adequate fluid resuscitation
    3. Arterial pH < 7.30 -OR >=3 Minor Criteria
    1. New onset of confusion or disorientation
    2. Hypothermia (core temperature <=36 C)
    3. Respiratory rate >=30 breaths/min
    4. Hypotension requiring aggressive fluid resuscitation
    5. Uremia (BUN >=20 mg/dL)
    6. PaO2: FiO2 ratio <=250 or SaO2:FiO2 ratio <=250
    7. Leukopenia (WBC count < 4000 cells/mm3)
    8. Platelet count < 100,000 cells/mm3 or > 400,000 cells/mm3
    9. Multilobar infiltrates

      Exclusion Criteria:

      - Patient's age 17 years or younger.

      - Vasopressor-dependent shock requiring moderate-to-high dose vasopressor (i.e., norepinephrine >=0.3 mcg/Kg/min) treatment for greater than 2 hours in patient that is adequately fluid-resuscitated (at least 4 liters of crystalloids) WITH central venous pressure (CVP) equal to or greater than 8 mm Hg for nonventilated patients and equal to or greater than 12 mm Hg for ventilated patients. (See explanation below)*

      - Major gastrointestinal bleeding requiring transfusion of 5 units or more of packed red blood cells within 3 months of current hospitalization.

      - Any condition requiring 20 mg of prednisone equivalent/day for greater than 14 days, over the last 3 months.

      - Chronic obstructive pulmonary disease (COPD) with acute exacerbation requiring glucocorticoid treatment at hospital admission. Patients with short-term glucocorticoid use (e.g., methylprednisolone up to 300 mg within 5 days of randomization) will not be excluded.

      - Patients enrolled in another experimental (interventional) protocol.

      - Pregnancy, confirmed by urine or serum test.

      - Presence of postobstructive pneumonia or cystic fibrosis.

      - Clinical history consistent with aspiration of gastric content (i.e., loss of consciousness or seizure).

      - Active tuberculosis or fungal infection.

      - Moribund patient (i.e., not expected to live more than 24 h) or with recent (within 7 days) cardiopulmonary arrest, or with (known or suspected) irreversible cessation of all brain function, or comfort measure status.

      - Presence of preexisting medical condition that is irreversible and expected to be fatal within 3 months.

      • Patients with severe immunosuppression (i.e., HIV with CD4 <200), neutropenia (less than 1000 neutrophils) not related to pneumonia, acute burn injury, or receiving immunosuppressive or cytotoxic therapy for any reason.
      • Chronic severe cognitive impairment caused by dementia or central nervous system pathologies (tumor, cerebro-vascular accident, infections, or head injuries) as defined by the site investigator by obtaining medical history and reviewing medical record.
      • The physician doesn't feel the patient is a viable candidate for the study (e.g., presence of hypersensitivity or previous severe adverse reaction to cosyntropin or any glucocorticoid, history of adrenal insufficiency or chronic systemic steroid use placing the patient at risk for relative adrenal insufficiency).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01283009

Show Show 30 study locations
Sponsors and Collaborators
VA Office of Research and Development
Layout table for investigator information
Study Chair: Gianfranco U Meduri, MD Memphis VA Medical Center, Memphis, TN
Publications automatically indexed to this study by Identifier (NCT Number):
Layout table for additonal information
Responsible Party: VA Office of Research and Development Identifier: NCT01283009    
Other Study ID Numbers: 574
First Posted: January 25, 2011    Key Record Dates
Results First Posted: October 8, 2020
Last Update Posted: October 8, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by VA Office of Research and Development:
Additional relevant MeSH terms:
Layout table for MeSH terms
Respiration Disorders
Respiratory Tract Diseases
Respiratory Tract Infections
Lung Diseases
Methylprednisolone Acetate
Methylprednisolone Hemisuccinate
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Anti-Inflammatory Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Neuroprotective Agents
Protective Agents
Antineoplastic Agents, Hormonal
Antineoplastic Agents