Extended Steroid in Use in Community Acquired Pneumonia (CAP)(e)
Status:
Completed
Trial end date:
2016-08-31
Target enrollment:
Participant gender:
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.