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Community-Acquired Pneumonia : Evaluation of Corticosteroids (CAPE_COD)

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ClinicalTrials.gov Identifier: NCT02517489
Recruitment Status : Unknown
Verified May 2017 by University Hospital, Tours.
Recruitment status was:  Recruiting
First Posted : August 7, 2015
Last Update Posted : May 10, 2017
Sponsor:
Information provided by (Responsible Party):
University Hospital, Tours

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.


Condition or disease Intervention/treatment Phase
Community Acquired Pneumonia Drug: Hydrocortisone Drug: Placebo Phase 3

Detailed Description:

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Effects of Low-dose Corticosteroids on Survival of Severe Community-acquired Pneumonia
Study Start Date : October 2015
Estimated Primary Completion Date : October 2018
Estimated Study Completion Date : December 2018


Arm Intervention/treatment
Experimental: Hydrocortisone
Patients in the treatment group will receive intra-venous hydrocortisone (in addition to the standard treatment of severe Community-Acquired Pneumonia (CAP)
Drug: 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.

Placebo Comparator: 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)
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.




Primary Outcome Measures :
  1. Day 28 all causes mortality [ Time Frame: at day 28 ]

Secondary Outcome Measures :
  1. In patients non-invasively ventilated at inclusion, proportion of patients needing endotracheal intubation [ Time Frame: Participants will be followed for the duration of hospital stay, for a maximum of 28 days ]
  2. In patients non-ventilated at inclusion, proportion of patients requiring non-invasive ventilation [ Time Frame: Participants will be followed for the duration of hospital stay, for a maximum of 28 days ]
  3. In patients non-ventilated at inclusion, proportion of patients needing endotracheal intubation [ Time Frame: Participants will be followed for the duration of hospital stay, for a maximum of 28 days ]
  4. Day 28 ventilator-free-days [ Time Frame: between 0 and day 28 ]
  5. Number of patients with vasopressor therapy initiation from inclusion to day 28 [ Time Frame: between 0 and day 28 ]
  6. Day 28 vasopressor-free-days [ Time Frame: between 0 and day 28 ]
  7. ICU and/or intermediate care unit LOS [ Time Frame: Participants will be followed for the duration of hospital stay, for a maximum of 28 days ]
  8. All-causes mortality at day 90 [ Time Frame: at day 90 ]
  9. SF-36 Health Survey at day 90 [ Time Frame: at day 90 ]
  10. Biomarkers: procalcitonin at baseline, day 3 and day 7 [ Time Frame: at inclusion, day 3 and day 7 ]
  11. Biomarkers: C-reactive protein at baseline, day 3 and day 7 [ Time Frame: at inclusion, day 3 and day 7 ]
  12. Biomarkers: plasmatic concentration of pro-inflammatory cytokines (IL-6, IL-20, IL-22, IL-22BP, HBD2, TNF) at baseline, day 3 and day 7 [ Time Frame: at inclusion, day 3 and day 7 ]
  13. P/F ratio measured daily from baseline to day 7, at the end of treatment, at the end of ICU-stay and/or day 28 [ Time Frame: measured daily from baseline to day 7, at the end of treatment i.e 14 days after the start of treatment, at the end of ICU-stay (for a maximum of 28 days) and/or day 28 ]
  14. SOFA calculated daily from baseline to day 7, at the end of treatment, at the end of ICU-stay and/or day 28 [ Time Frame: calculated daily from baseline to day 7, at the end of treatment (i.e 14 days after the start of treatment), at the end of ICU-stay (for a maximum of 28 days) and/or day 28 ]
  15. Proportion of patients experiencing secondary infection during their ICU-stay [ Time Frame: Participants will be followed for the duration of hospital stay, for a maximum of 28 days ]
  16. Proportion of patients experiencing gastrointestinal bleeding during their ICU-stay [ Time Frame: Participants will be followed for the duration of hospital stay, for a maximum of 28 days ]
  17. Daily amount of insulin administered to the patient from day 1 to day 7 [ Time Frame: Patients will be followed from day 1 to day 7 ]
  18. Weight-gain at baseline and day 7 [ Time Frame: Patients will be followed at baseline and day 7 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 PaO2/FiO2 (P/F) ratio lower than 200
  • Patient already treated by antibiotics (at least one dose)
  • Informed consent signed by the patient, its relatives or emergency procedure

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 five 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
  • Pregnant or breastfeeding woman
  • Patient on judicial protection

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02517489


Contacts
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Contact: Pierre-François DEQUIN, MD-PhD 02.47.47.38.55 ext +33 pierre-françois.dequin@univ-tours.fr
Contact: Marie LECLERC 02.47.47.46.64 ext +33 m.leclerc@chu-tours.fr

Locations
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France
Service de Réanimation - Unité de Soins Continus, CH d'Angoulême Recruiting
'Angoulême, France, 16959
Contact: Christophe CRACCO, MD         
Principal Investigator: Christophe CRACCO, MD         
Service de Réanimation Polyvalente, CH d'Argenteuil Recruiting
Argenteuil, France, 95107
Contact: Gaëtan PLANTEFEVE, MD         
Principal Investigator: Gaëtan PLANTEFEVE, MD         
Service de Réanimation HIA Clermont-Tonnerre Recruiting
Brest, France, 29240
Contact: Christophe GIACARDI, MD         
Principal Investigator: Christophe GIACARDI, MD         
Service de Réanimation Médicale, CHU de Brest Recruiting
Brest, France, 29609
Contact: Erwann L'HER, MD-PhD         
Principal Investigator: Erwann L'HER, MD-PhD         
Service de Réanimation Médicale, Hôpital Louis Pasteur, Chartres Not yet recruiting
Chartres, France, 28000
Contact: Abdelkader OUCHENIR, MD         
Principal Investigator: Abdelkader OUCHENIR, MD         
Service de Réanimation Médicale Polyvalente, Hôpital G Montpied Recruiting
Clermont Ferrand, France, 63003
Contact: Bertrand SOUWEINE, MCU-PH         
Principal Investigator: Bertrand SOUWEINE, MCU-PH         
Service de Réanimation, Hôpital Louis Mourier Recruiting
Colombes, France, 92700
Contact: Jean-Damien RICARD, MCU-PH         
Principal Investigator: Jean-Damien RICARD, MCU-PH         
Service de Réanimation Médicale, CHU de Dijon Recruiting
Dijon, France, 21079
Contact: Jean-Pierre QUENOT, MD         
Principal Investigator: Jean-Pierre QUENOT, MD         
Service de Réanimation Médico-Chirurgicale, Hôpital Raymond Poincarré, APHP Recruiting
Garches, France, 92380
Contact: Djillali ANNANE, MD-PhD         
Principal Investigator: Djillali ANNANE, MD-PhD         
Service de Réanimation Médicale, CHU de Grenoble Recruiting
Grenoble, France, 38043
Contact: Nicolas TERZI, MD         
Principal Investigator: Nicolas TERZI, MD         
Service de Réanimation Polyvalente, CHD La Roche sur Yon Recruiting
La Roche sur Yon, France, 85925
Contact: Jean REIGNIER, MD         
Principal Investigator: Jean REIGNIER, MD         
Service de Réanimation Polyvalente, Hôpital Salengro, CHU de Lille Recruiting
Lille, France, 59037
Contact: Mercé JOURDAIN, MD-PhD         
Principal Investigator: Mercé JOURDAIN, MD-PhD         
Service de Réanimation Polyvalente, CHU de Limoges Recruiting
Limoges, France, 87042
Contact: Bruno François, MD         
Principal Investigator: Bruno François, MD         
Service de Réanimation Médicale, Hôpital Nord Recruiting
Marseille, France, 13015
Contact: Laurent PAPAZIAN, MCU-PH         
Principal Investigator: Laurent PAPAZIAN, MCU-PH         
Service de Réanimation Polyvalente - Surveillance Continue, CH de Montauban Recruiting
Montauban, France, 82013
Contact: Frédéric BELLEC, MD         
Principal Investigator: Frédéric BELLEC, MD         
Service de Réanimation Médicale, CHU de Nancy Recruiting
Nancy, France, 54511
Contact: Sébastien GIBOT, MD-PhD         
Principal Investigator: Sébastien GIBOT, MD-PhD         
Service de Réanimation Polyvalente, Hôpital Hôtel Dieu, CHU de Nantes Recruiting
Nantes, France, 44093
Contact: Christophe GUITTON, MD         
Principal Investigator: Christophe GUITTON, MD         
Service de Réanimation Médicale, CHR d'Orléans Recruiting
Orléans, France, 45067
Contact: Thierry BOULAIN, MD         
Principal Investigator: Thierry BOULAIN, MD         
Service de Réanimation Médicale, Hôpital Cochin, APHP Recruiting
Paris, France, 75014
Contact: Jean-Paul MIRA, MD-PhD         
Principal Investigator: Jean-Paul MIRA, MD-PhD         
Service de Réanimation et USC médico-chirurgicale, Hôpital Tenon, APHP Recruiting
Paris, France, 75020
Contact: Muriel-Sarah FARTOUKH, MD-PhD         
Principal Investigator: Muriel-Sarah FARTOUKH, MD-PhD         
Service de Réanimation Médicale et Médecine Interne, CHU de Poitiers Recruiting
Poitiers, France, 86021
Contact: Jean-Pierre FRAT, MD         
Principal Investigator: Jean-Pierre FRAT, MD         
Service des Maladies Infectieuses et Réanimation Médicale, CHU de Rennes Recruiting
Rennes, France, 35033
Contact: Arnaud GACOUIN, MD         
Principal Investigator: Arnaud GACOUIN, MD         
Service de Réanimation Polyvalente, CH de Saint Malo Recruiting
Saint Malo, France, 35403
Contact: Stéphanie CHEVALIER, MD         
Principal Investigator: Stéphanie CHEVALIER, MD         
Service de Réanimation Recruiting
Saint-Brieuc, France, 22000
Contact: Nicolas BARBAROT, MD         
Principal Investigator: Nicolas BARBAROT, MD         
Service de Réanimation Médicale, Nouvel Hôpital Civil, CHU de Strasbourg Recruiting
Strasbourg, France, 67091
Contact: Ferhat MEZIANI, MD-PhD         
Principal Investigator: Ferhat MEZIANI, MD-PhD         
Service de Réanimation Médicale, Hôpital de Hautepierre, CHU de Strasbourg Recruiting
Strasbourg, France, 67098
Contact: Francis SCHNEIDER, MD-PhD         
Principal Investigator: Francis SCHNEIDER, MD-PhD         
Sponsors and Collaborators
University Hospital, Tours
Investigators
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Principal Investigator: Pierre-François DEQUIN, MD-PhD CHRU de TOURS

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Responsible Party: University Hospital, Tours
ClinicalTrials.gov Identifier: NCT02517489     History of Changes
Other Study ID Numbers: PHRN14-PFD/CAPE COD
First Posted: August 7, 2015    Key Record Dates
Last Update Posted: May 10, 2017
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University Hospital, Tours:
Community-Acquired Pneumonia (CAP)
Hydrocortisone
Corticosteroids

Additional relevant MeSH terms:
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Pneumonia
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Hydrocortisone
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone acetate
Hydrocortisone hemisuccinate
Anti-Inflammatory Agents