Community-Acquired Pneumonia : Evaluation of Corticosteroids
CAPE_COD
Effects of Low-dose Corticosteroids on Survival of Severe Community-acquired Pneumonia
1 other identifier
interventional
952
1 country
32
Brief Summary
Mortality of severe Community-Acquired Pneumonia (CAP) has not declined over time and is between 25 and 30% in sub-groups of patients. Corticosteroids (CTx) could down-regulate pulmonary and systemic inflammation, accelerate clinical resolution and decrease the rate of inflammation-associated systemic complications. Two recent meta-analyses suggest a positive effect on severe CAP day 28 survival when CTx are added to standard therapy. However they are based on only four trials gathering less than 300 patients, of which only one was positive. Recently published guidelines do not recommend CTx as part of CAP treatment. Therefore a well-powered trial appears necessary to test the hypothesis that CTx - and more specifically hydrocortisone - could improve day 28 survival of critically-ill patients with severe CAP, severity being assessed either on a Pulmonary Severity Index ≥ 130 (Fine class V) or by the use of mechanical ventilation or high-FiO2 high-flow oxygen therapy. A phase-III multicenter add-on randomized controlled double-blind superiority trial assessing the efficacy of hydrocortisone vs. placebo on Day 28 all-causes mortality, in addition to antibiotics and supportive care, including the correction of hypoxemia. Randomization will be stratified on: (i) centers; (ii) use of mechanical ventilation at the time of inclusion.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Oct 2015
Longer than P75 for phase_3
32 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 31, 2015
CompletedFirst Posted
Study publicly available on registry
August 7, 2015
CompletedStudy Start
First participant enrolled
October 28, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 19, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
August 28, 2020
CompletedDecember 22, 2025
January 1, 2023
4.7 years
July 31, 2015
December 15, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Day 28 all causes mortality
at day 28
Day 21 failure
For the sub-group of patients included with COVID19, failure is defined as death or need of respiratory support (mechanical ventilation or high-flow oxygen therapy);
at day 21
Secondary Outcomes (18)
In patients non-invasively ventilated at inclusion, proportion of patients needing endotracheal intubation
Participants will be followed for the duration of hospital stay, for a maximum of 28 days
In patients non-ventilated at inclusion, proportion of patients requiring non-invasive ventilation
Participants will be followed for the duration of hospital stay, for a maximum of 28 days
In patients non-ventilated at inclusion, proportion of patients needing endotracheal intubation
Participants will be followed for the duration of hospital stay, for a maximum of 28 days
Day 28 ventilator-free-days
between 0 and day 28
Number of patients with vasopressor therapy initiation from inclusion to day 28
between 0 and day 28
- +13 more secondary outcomes
Other Outcomes (3)
P/F ratio measured daily from Day1 to Day7, at Day 14 and at Day 21 and/or at the end of ICU-stay
from day 1 to day 7, at day 14 and day 21 and/or at the end of ICU-stay
Proportion of patients needing endotracheal intubation
at day 21
Proportion of patients experiencing secondary infection during their ICU-stay
From baseline to day 21
Study Arms (2)
Hydrocortisone
EXPERIMENTALPatients in the treatment group will receive intra-venous hydrocortisone (in addition to the standard treatment of severe Community-Acquired Pneumonia (CAP)
Placebo
PLACEBO COMPARATORPatients of the control group will receive an intravenous placebo by intravenous route (in addition to the standard treatment of severe Community-Acquired Pneumonia (CAP)
Interventions
Hydrocortisone will be given in a double-blind fashion for 8 or 14 full days. The intravenous route will be used. The treatment course will include 4 or 7 days of full dose (200 mg/day by continuous infusion), 2 or 4 days of half dose (100 mg/day by continuous infusion), and 2 or 3 days of tapering dose (50 mg/day by continuous infusion). Duration of treatment is chosen upon patient initial improvement.
Placebo will be given in a double-blind fashion for 8 or 14 full days. The intravenous route will be used. The treatment course will include 4 or 7 days of full dose (200 mg/day by continuous infusion), 2 or 4 days of half dose (100 mg/day by continuous infusion), and 2 or 3 days of tapering dose (50 mg/day by continuous infusion). Duration of treatment is chosen upon patient initial improvement.
Eligibility Criteria
You may qualify if:
- Age ≥ 18 years
- Patients affiliated to social security scheme
- Admission to an Intensive Care Unit (ICU) or intermediate care unit participating to the trial
- Diagnosis of Community- Acquired Pneumonia (CAP) suggested by at least two of the following: cough, purulent sputum, chest pain and dyspnea
- Focal shadowing/infiltrate on chest X-ray or CT-scan
- Diagnosis of Community- Acquired Pneumonia (CAP) during the 48 hours post-hospital admission
- Study drug infusion initiated no longer than 24 hours post first severity criterion
- Severity defined by at least one of the following:
- Pneumonia Severity Index (PSI) \> 130 (Fine class V)
- Patient placed on mechanical ventilation (invasive or not) for acute respiratory failure, with a PEEP level of 5 cm of water or more
- Patient treated by high-flow oxygen therapy with a FiO2 of 50% or more and a P/F ratio less than 300
- Patient treated by oxygen therapy with a partial rebreathing-mask with a reservoir bag, provided that the PaO2 is less than (cf. table):
- Oxygen flow (L/min) 6 7 8 9 10 or more PaO2 (mmHg) less than 180 210 240 270 300
- Patient already treated by antibiotics (at least one dose since admission to hospital)
- Informed consent signed by the patient, its relatives or emergency procedure
- +4 more criteria
You may not qualify if:
- Clinical history suggesting of aspiration of gastric content
- Patient treated by invasive mechanical ventilation within 14 days before current hospital admission
- Patient treated by antibiotics for a respiratory infection for more than seven days at the admission to the hospital (except if a pathogen resistant to this antibiotics is isolated)
- History of cystic fibrosis
- Post-obstructive pneumonia
- Patients in which rapid PCR-test is positive for flu
- Active tuberculosis or fungal infection
- Active viral hepatitis or active infection with herpes viruses
- Myelosuppression
- Decision of withholding mechanical ventilation or endotracheal intubation
- Hypersensitivity to corticosteroids
- Patient needing anti-inflammatory corticosteroids or substitutive hydrocortisone for any reason
- Patients under treatment by more than 15 mg/d of prednisone (or equivalent) for more than 30 days
- Pregnant or breastfeeding woman
- Patient on judicial protection
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (32)
Service de Réanimation - Unité de Soins Continus, CH d'Angoulême
Angoulême, 16959, France
Service de Réanimation Polyvalente, CH d'Argenteuil
Argenteuil, 95107, France
Service de Réanimation, CHR Metz-Thionville
Ars-Laquenexy, 57530, France
Service de Réanimation
Aulnay-sous-Bois, 93602, France
Service de Réanimation
Belfort, 90015, France
Service de Réanimation
Bourg-en-Bresse, France
Service de Réanimation HIA Clermont-Tonnerre
Brest, 29240, France
Service de Réanimation Médicale, CHU de Brest
Brest, 29609, France
Service de Réanimation, CHU Côte de Nacre
Caen, 14033, France
Service de Réanimation Médicale, Hôpital Louis Pasteur, Chartres
Chartres, 28000, France
Service de Réanimation Médicale Polyvalente, Hôpital G Montpied
Clermont-Ferrand, 63003, France
Service de Réanimation, Hôpital Louis Mourier
Colombes, 92700, France
Service de Réanimation Médicale, CHU de Dijon
Dijon, 21079, France
Service de Réanimation Médico-Chirurgicale, Hôpital Raymond Poincarré, APHP
Garches, 92380, France
Service de Réanimation Médicale, CHU de Grenoble
Grenoble, 38043, France
Service de Réanimation Polyvalente, CHD La Roche sur Yon
La Roche-sur-Yon, 85925, France
Service de Réanimation, CH Le Mans
Le Mans, 72037, France
Service de Réanimation Polyvalente, Hôpital Salengro, CHU de Lille
Lille, 59037, France
Service de Réanimation Polyvalente, CHU de Limoges
Limoges, 87042, France
Service de Réanimation Médicale, Hôpital Nord
Marseille, 13015, France
Service de Réanimation Polyvalente - Surveillance Continue, CH de Montauban
Montauban, 82013, France
Service de Réanimation Médicale, CHU de Nancy
Nancy, 54511, France
Service de Réanimation Polyvalente, Hôpital Hôtel Dieu, CHU de Nantes
Nantes, 44093, France
Service de Réanimation Médicale, CHR d'Orléans
Orléans, 45067, France
Service de Réanimation Médicale, Hôpital Cochin, APHP
Paris, 75014, France
Service de Réanimation et USC médico-chirurgicale, Hôpital Tenon, APHP
Paris, 75020, France
Service de Réanimation Médicale et Médecine Interne, CHU de Poitiers
Poitiers, 86021, France
Service des Maladies Infectieuses et Réanimation Médicale, CHU de Rennes
Rennes, 35033, France
Service de Réanimation
Saint-Brieuc, 22000, France
Service de Réanimation Polyvalente, CH de Saint Malo
St-Malo, 35403, France
Service de Réanimation Médicale, Nouvel Hôpital Civil, CHU de Strasbourg
Strasbourg, 67091, France
Service de Réanimation Médicale, Hôpital de Hautepierre, CHU de Strasbourg
Strasbourg, 67098, France
Related Publications (3)
Dequin PF, Heming N, Meziani F, Plantefeve G, Voiriot G, Badie J, Francois B, Aubron C, Ricard JD, Ehrmann S, Jouan Y, Guillon A, Leclerc M, Coffre C, Bourgoin H, Lengelle C, Caille-Fenerol C, Tavernier E, Zohar S, Giraudeau B, Annane D, Le Gouge A; CAPE COVID Trial Group and the CRICS-TriGGERSep Network. Effect of Hydrocortisone on 21-Day Mortality or Respiratory Support Among Critically Ill Patients With COVID-19: A Randomized Clinical Trial. JAMA. 2020 Oct 6;324(13):1298-1306. doi: 10.1001/jama.2020.16761.
PMID: 32876689RESULTFriedrich JO, Gouvea Bogossian E. Hydrocortisone in Severe Community-Acquired Pneumonia. N Engl J Med. 2023 Aug 17;389(7):670-671. doi: 10.1056/NEJMc2307400. No abstract available.
PMID: 37585638DERIVEDDequin PF, Meziani F, Quenot JP, Kamel T, Ricard JD, Badie J, Reignier J, Heming N, Plantefeve G, Souweine B, Voiriot G, Colin G, Frat JP, Mira JP, Barbarot N, Francois B, Louis G, Gibot S, Guitton C, Giacardi C, Hraiech S, Vimeux S, L'Her E, Faure H, Herbrecht JE, Bouisse C, Joret A, Terzi N, Gacouin A, Quentin C, Jourdain M, Leclerc M, Coffre C, Bourgoin H, Lengelle C, Caille-Fenerol C, Giraudeau B, Le Gouge A; CRICS-TriGGERSep Network. Hydrocortisone in Severe Community-Acquired Pneumonia. N Engl J Med. 2023 May 25;388(21):1931-1941. doi: 10.1056/NEJMoa2215145. Epub 2023 Mar 21.
PMID: 36942789DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Pierre-François DEQUIN, MD-PhD
CHRU de TOURS
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 31, 2015
First Posted
August 7, 2015
Study Start
October 28, 2015
Primary Completion
July 19, 2020
Study Completion
August 28, 2020
Last Updated
December 22, 2025
Record last verified: 2023-01
Data Sharing
- IPD Sharing
- Will not share