Community-Acquired Pneumonia : Evaluation of Corticosteroids

NCT ID: NCT02517489

Last Updated: 2025-12-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

952 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-10-28

Study Completion Date

2020-08-28

Brief Summary

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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.

Detailed Description

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Patients will receive state-of-the-art standard therapy for severe Community-Acquired Pneumonia (CAP), including antibiotics and supportive care. Correction of hypoxemia will use standard low-flow oxygen therapy, high-flow oxygen therapy, non-invasive-ventilation or invasive ventilation with endotracheal tube, as required. Patients in the treatment group will receive intra-venous hydrocortisone. Patients of the control group will receive an intravenous placebo by intravenous route at the same frequency.

Hydrocortisone or 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.

A substantial amendment to the CAPE COD study has been submitted to the Competent Authorities in order to conduct a specific analysis on the sub-group of patients included with COVID19 (coronavirus disease 2019), in order to get a quick response in this specific population and in the context of an epidemic emergency.

The aim is to answer as quickly as possible a therapeutic question of major importance in the treatment of severe respiratory infections with CoV-2 SARS (severe acute respiratory syndrome coronavirus 2). Modifications made to the original study for patients with COVID (coronavirus disease) include some inclusion criteria, the primary endpoint, and secondary endpoints.

Conditions

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Community Acquired Pneumonia

Keywords

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Community-Acquired Pneumonia (CAP) Hydrocortisone Corticosteroids COronaVIrus Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Hydrocortisone

Patients in the treatment group will receive intra-venous hydrocortisone (in addition to the standard treatment of severe Community-Acquired Pneumonia (CAP)

Group Type EXPERIMENTAL

Hydrocortisone

Intervention Type DRUG

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

Patients of the control group will receive an intravenous placebo by intravenous route (in addition to the standard treatment of severe Community-Acquired Pneumonia (CAP)

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

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.

Interventions

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Hydrocortisone

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.

Intervention Type DRUG

Placebo

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.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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

On the sub-group of patients included with COVID19 :

* Diagnosis of COVID19 either as certain (PCR) or probable (evocative clinical and radiological features AND epidemic context AND absence of other microbiological documentation).
* Study drug infusion initiated no longer than 24 hours post first severity criterion ; in case of transfer from another hospital, this period will be prolonged to 48 hours
* Patient receiving the best available treatment as define by up-to-date scientific knowledge

Exclusion Criteria

* Patient treated by vasopressors for septic shock at the time of inclusion
* 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
* Patient already enrolled in another drug trial with mortality as an end-point. If the patient is already participating in another therapeutic trial with a different endpoint, the investigator must verify that inclusion in CAPE COD can not prejudice it.
* Pregnant or breastfeeding woman
* Patient on judicial protection
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Hospital, Tours

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Pierre-François DEQUIN, MD-PhD

Role: PRINCIPAL_INVESTIGATOR

CHRU de TOURS

Locations

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Service de Réanimation - Unité de Soins Continus, CH d'Angoulême

Angoulême, , France

Site Status

Service de Réanimation Polyvalente, CH d'Argenteuil

Argenteuil, , France

Site Status

Service de Réanimation, CHR Metz-Thionville

Ars-Laquenexy, , France

Site Status

Service de Réanimation

Aulnay-sous-Bois, , France

Site Status

Service de Réanimation

Belfort, , France

Site Status

Service de Réanimation

Bourg-en-Bresse, , France

Site Status

Service de Réanimation HIA Clermont-Tonnerre

Brest, , France

Site Status

Service de Réanimation Médicale, CHU de Brest

Brest, , France

Site Status

Service de Réanimation, CHU Côte de Nacre

Caen, , France

Site Status

Service de Réanimation Médicale, Hôpital Louis Pasteur, Chartres

Chartres, , France

Site Status

Service de Réanimation Médicale Polyvalente, Hôpital G Montpied

Clermont-Ferrand, , France

Site Status

Service de Réanimation, Hôpital Louis Mourier

Colombes, , France

Site Status

Service de Réanimation Médicale, CHU de Dijon

Dijon, , France

Site Status

Service de Réanimation Médico-Chirurgicale, Hôpital Raymond Poincarré, APHP

Garches, , France

Site Status

Service de Réanimation Médicale, CHU de Grenoble

Grenoble, , France

Site Status

Service de Réanimation Polyvalente, CHD La Roche sur Yon

La Roche-sur-Yon, , France

Site Status

Service de Réanimation, CH Le Mans

Le Mans, , France

Site Status

Service de Réanimation Polyvalente, Hôpital Salengro, CHU de Lille

Lille, , France

Site Status

Service de Réanimation Polyvalente, CHU de Limoges

Limoges, , France

Site Status

Service de Réanimation Médicale, Hôpital Nord

Marseille, , France

Site Status

Service de Réanimation Polyvalente - Surveillance Continue, CH de Montauban

Montauban, , France

Site Status

Service de Réanimation Médicale, CHU de Nancy

Nancy, , France

Site Status

Service de Réanimation Polyvalente, Hôpital Hôtel Dieu, CHU de Nantes

Nantes, , France

Site Status

Service de Réanimation Médicale, CHR d'Orléans

Orléans, , France

Site Status

Service de Réanimation Médicale, Hôpital Cochin, APHP

Paris, , France

Site Status

Service de Réanimation et USC médico-chirurgicale, Hôpital Tenon, APHP

Paris, , France

Site Status

Service de Réanimation Médicale et Médecine Interne, CHU de Poitiers

Poitiers, , France

Site Status

Service des Maladies Infectieuses et Réanimation Médicale, CHU de Rennes

Rennes, , France

Site Status

Service de Réanimation

Saint-Brieuc, , France

Site Status

Service de Réanimation Polyvalente, CH de Saint Malo

St-Malo, , France

Site Status

Service de Réanimation Médicale, Nouvel Hôpital Civil, CHU de Strasbourg

Strasbourg, , France

Site Status

Service de Réanimation Médicale, Hôpital de Hautepierre, CHU de Strasbourg

Strasbourg, , France

Site Status

Countries

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France

References

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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.

Reference Type RESULT
PMID: 32876689 (View on PubMed)

Friedrich 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.

Reference Type DERIVED
PMID: 37585638 (View on PubMed)

Dequin 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.

Reference Type DERIVED
PMID: 36942789 (View on PubMed)

Provided Documents

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Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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PHRN14-PFD/CAPE COD

Identifier Type: -

Identifier Source: org_study_id