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NCT01283009: ESCAPe

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

Completed Phase 3 Results posted Last updated 8 October 2020
What this trial tests

Phase 3 trial testing Inactive Substance in Community Acquired Respiratory Disease Syndrome in 584 participants. Completed in 31 August 2016.

Timeline
9 January 2012
Primary endpoint
31 July 2016
31 August 2016

Quick facts

Lead sponsorVA Office of Research and Development
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment584
Start date9 January 2012
Primary completion31 July 2016
Estimated completion31 August 2016
Sites30 locations across Puerto Rico, United States

Drugs / interventions tested

Conditions studied

Sponsor

VA Office of Research and Development — full company profile →

Who can join

18 and older, any sex, with Community Acquired Respiratory Disease Syndrome. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

60-day Mortality Primary · 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.

Died on or prior to study day 60
GroupValue95% CI
Arm 1: Inactive Substance50
Arm 2: Methylprednisolone47
Arm 1: Inactive Substance227
Arm 2: Methylprednisolone239
Arm 1: Inactive Substance10
Arm 2: Methylprednisolone11
On Mechanical Ventilation at Study Entry
GroupValue95% CI
Arm 1: Inactive Substance24
Arm 2: Methylprednisolone22
Arm 1: Inactive Substance70
Arm 2: Methylprednisolone72
Arm 1: Inactive Substance2
Arm 2: Methylprednisolone3
Not on Mechanical Ventilation
GroupValue95% CI
Arm 1: Inactive Substance26
Arm 2: Methylprednisolone25
Arm 1: Inactive Substance157
Arm 2: Methylprednisolone167
Arm 1: Inactive Substance8
Arm 2: Methylprednisolone8

Adverse events — posted to ClinicalTrials.gov

Time frame: All SAEs were reported from Randomization to day 180.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Arm 1: Inactive Substance
Serious: 162/287 (56%)
Deaths: 84/287
Arm 2: Methylprednisolone
Serious: 167/297 (56%)
Deaths: 79/297

Serious adverse events (236 terms)

ReactionSystemArm 1: Inactive SubstanceArm 2: Methylprednisolone
PneumoniaInfections and infestations
Cardiac failure congestiveCardiac disorders
Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders
Acute kidney injuryRenal and urinary disorders
Multiple organ dysfunction syndromeGeneral disorders
Respiratory failureRespiratory, thoracic and mediastinal disorders
Pneumonia aspirationRespiratory, thoracic and mediastinal disorders
Acute myocardial infarctionCardiac disorders
Urinary tract infectionInfections and infestations
Cerebrovascular accidentNervous system disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
AnaemiaBlood and lymphatic system disorders
Atrial fibrillationCardiac disorders
Cardiac failureCardiac disorders
Clostridium difficile colitisInfections and infestations
SepsisInfections and infestations
DeliriumPsychiatric disorders
Mental status changesPsychiatric disorders
Acute respiratory distress syndromeRespiratory, thoracic and mediastinal disorders
Pleural effusionRespiratory, thoracic and mediastinal disorders
Gastrointestinal haemorrhageGastrointestinal disorders
Adverse drug reactionGeneral disorders
CellulitisInfections and infestations
Septic shockInfections and infestations
DehydrationMetabolism and nutrition disorders

Most-reported serious reactions: Pneumonia, Cardiac failure congestive, Chronic obstructive pulmonary disease, Acute kidney injury, Multiple organ dysfunction syndrome, Respiratory failure, Pneumonia aspiration, Acute myocardial infarction.

Data from ClinicalTrials.gov NCT01283009 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Diagnosis and Treatment of Adults with Community-acquired Pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America.
    Metlay JP, Waterer GW, Long AC, Anzueto A, et al · · 2019 · cited 2326× · PMID 31573350 · DOI 10.1164/rccm.201908-1581st
  2. Corticosteroids for pneumonia.
    Stern A, Skalsky K, Avni T, Carrara E, et al · · 2017 · cited 157× · PMID 29236286 · DOI 10.1002/14651858.cd007720.pub3
  3. Diagnosis and treatment of acute pulmonary inflammation in critically ill patients: The role of inflammatory biomarkers.
    Chalmers S, Khawaja A, Wieruszewski PM, Gajic O, et al · · 2019 · cited 47× · PMID 31559145 · DOI 10.5492/wjccm.v8.i5.59
  4. Effectiveness of a Bundled Intervention Including Adjunctive Corticosteroids on Outcomes of Hospitalized Patients With Community-Acquired Pneumonia: A Stepped-Wedge Randomized Clinical Trial.
    Lloyd M, Karahalios A, Janus E, Skinner EH, et al · · 2019 · cited 41× · PMID 31282921 · DOI 10.1001/jamainternmed.2019.1438
  5. Recent advances in our understanding of Streptococcus pneumoniae infection.
    Feldman C, Anderson R. · · 2014 · cited 41× · PMID 25343039 · DOI 10.12703/p6-82
  6. Corticosteroids in Community-Acquired Bacterial Pneumonia: a Systematic Review, Pairwise and Dose-Response Meta-Analysis.
    Pitre T, Abdali D, Chaudhuri D, Pastores SM, et al · · 2023 · cited 31× · PMID 37076606 · DOI 10.1007/s11606-023-08203-6
  7. Real-world corticosteroid use in severe pneumonia: a propensity-score-matched study.
    Ceccato A, Russo A, Barbeta E, Oscanoa P, et al · · 2021 · cited 16× · PMID 34915895 · DOI 10.1186/s13054-021-03840-x
  8. Statistical Considerations for Sequential Analysis of the Restricted Mean Survival Time for Randomized Clinical Trials.
    Lu Y, Tian L. · · 2021 · cited 14× · PMID 33927801 · DOI 10.1080/19466315.2020.1816491

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