Extended Steroid in CAP(e) (ESCAPe)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Department of Veterans Affairs
Sponsor:
Information provided by (Responsible Party):
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT01283009
First received: January 21, 2011
Last updated: September 18, 2014
Last verified: September 2014
  Purpose

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 and 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 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). We 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 Intervention Phase
Community Acquired Respiratory Disease Syndrome
Drug: Methylprednisolone
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: CSP #574 - Evaluate the Safety and Efficacy of Methylprednisolone in Hospitalized Veterans With Severe Community-Acquired Pneumonia

Resource links provided by NLM:


Further study details as provided by Department of Veterans Affairs:

Primary Outcome Measures:
  • All cause mortality [ Time Frame: 60-day ] [ Designated as safety issue: Yes ]
    The primary outcome is all-cause mortality at 60 days, defined by whether the patient has died by the end of study day 60.


Estimated Enrollment: 1450
Study Start Date: January 2012
Estimated Study Completion Date: January 2018
Estimated Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm 1
Methylprednisolone
Drug: Methylprednisolone
Methylprednisolone or placebo 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
Placebo Comparator: Arm 2
Inactive substance
Drug: Methylprednisolone
Methylprednisolone or placebo 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

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  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient's origin. Patients are classified as having 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 greater than 38 C oral (>38.5 C rectally or tympanically) or hypothermia (<35 C) White blood cell count greater than 10,000 cells/mm3 or less than 4,500 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 IDSA/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.
  • 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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01283009

Contacts
Contact: Lisa Bridges, MSN (901) 577-7597 lisa.bridges2@va.gov

  Show 43 Study Locations
Sponsors and Collaborators
Investigators
Study Chair: Gianfranco Umberto Meduri, MD VA Medical Center, Memphis
  More Information

No publications provided

Responsible Party: Department of Veterans Affairs
ClinicalTrials.gov Identifier: NCT01283009     History of Changes
Other Study ID Numbers: 574
Study First Received: January 21, 2011
Last Updated: September 18, 2014
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by Department of Veterans Affairs:
Mycoplasma pneumoniae

Additional relevant MeSH terms:
Respiratory Tract Diseases
Respiration Disorders
Methylprednisolone acetate
Prednisolone acetate
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Neuroprotective Agents
Protective Agents
Antineoplastic Agents, Hormonal
Antineoplastic Agents

ClinicalTrials.gov processed this record on September 22, 2014