Low Doses Corticosteroids as Adjuvant Therapy for the Treatment of Severe H1N1 Flu (CORTIFLU)

• ClinicalTrials.gov Identifier: NCT01014364
• Recruitment Status: Terminated
• First Posted: November 17, 2009
• Last Update Posted: December 18, 2014
• Sponsor: University of Versailles
• Collaborator: Assistance Publique - Hôpitaux de Paris
• Information provided by (Responsible Party): Djillali Annane, University of Versailles

Tracking Information

• First Submitted Date: November 16, 2009
• First Posted Date: November 17, 2009
• Last Update Posted Date: December 18, 2014
• Study Start Date: March 2010
• Actual Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: December 17, 2014): in hospital all cause morality [ Time Frame: hospital discharge up to 90 days ]
• Original Primary Outcome Measures (submitted: November 16, 2009): in hospital all cause morality [ Time Frame: hospital discharge ]

Current Secondary Outcome Measures (submitted: December 17, 2014)

• 28 day mortality [ Time Frame: 28 day ]
• 90 day all cause mortality [ Time Frame: 90 day ]
• 6 month all cause mortality [ Time Frame: 180 days ]
• mechanical ventilation free days [ Time Frame: hospital discharge up to 90 days ]
• intensive care unit free days [ Time Frame: hospital discharge up to 90 days ]
• proportion of patients with secondary infections [ Time Frame: hospital discharge up to 90 days ]
• proportion of patients who require ECMO [ Time Frame: hospital discharge up to 90 days ]
• respiratory function and health status [ Time Frame: 180 days ]

Original Secondary Outcome Measures (submitted: November 16, 2009)

• 28 day mortality [ Time Frame: 28 day ]
• 90 day all cause mortality [ Time Frame: 90 day ]
• 6 month all cause mortality [ Time Frame: 180 days ]
• mechanical ventilation free days [ Time Frame: hospital discharge ]
• intensive care unit free days [ Time Frame: hospital discharge ]
• proportion of patients with secondary infections [ Time Frame: hospital discharge ]
• proportion of patients who require ECMO [ Time Frame: hospital discharge ]
• respiratory function and health status [ Time Frame: 180 days ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Low Doses Corticosteroids as Adjuvant Therapy for the Treatment of Severe H1N1 Flu
• Official Title: Phase III Study of Hydrocortisone in Patients With Severe H1N1 Related Pneumonia
• Brief Summary: The H1N1 flu pandemic is one of the major infectious threat of the past half century. it is rapidly progressing worldwide and a substantial number of patients get severe H1N1 related pneumonia that requires mechanical ventilation and admission to the intensive care unit. The acute respiratory distress syndrome is associated with a substantial mortality and morbidity partly as a consequence of uncontrolled lung and systemic inflammation. many physicians are trying to counteract this pro-inflammatory storm by the use of corticosteroids albeit these drugs may cause super infection or metabolic disorders. Thus, there is a need for a randomized double blind, placebo controlled trial to define the benefit to risk ratio of corticosteroids in this patient.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Pneumonia, Viral
• Influenza in Humans

Intervention

• Drug: hydrocortisone
  50mg intravenous bolus every 6 hours for one week, then every 12 hours for one week and then every 24 hours for one week
  Other Name: hydrocortisone acetate
• Drug: isotonic saline
  intravenous bolus every 6 hours for one week, then every 12 hours for one week and then every 24 hours for one week
  Other Name: normal saline

Study Arms

• Experimental: Corticosteroids
  Hydrocortisone
  Intervention: Drug: hydrocortisone
• Placebo Comparator: Control
  isotonic saline
  Intervention: Drug: isotonic saline

• Publications *: Annane D, Antona M, Lehmann B, Kedzia C, Chevret S; CORTIFLU Investigators; CRICs; AZUREA; REVA/SRLF networks. Designing and conducting a randomized trial for pandemic critical illness: the 2009 H1N1 influenza pandemic. Intensive Care Med. 2012 Jan;38(1):29-39. doi: 10.1007/s00134-011-2409-8. Epub 2011 Nov 26.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: December 17, 2014): 40
• Original Estimated Enrollment (submitted: November 16, 2009): 448
• Actual Study Completion Date: December 2011
• Actual Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• age above 15 years old
• admitted to intensive care unit
• proven or strong suspicion of H1N1 Influenza infection
• diffuse pneumonia (for less than 96 hours)
• need for non invasive or invasive mechanical ventilation

Exclusion Criteria:

• pregnancy
• an age of 15 or less
• rapidly fatal underlying disease with a life expectancy of one month or less
• more than 3 organ dysfunction upon admission
• previous treatment with corticosteroids (ie prednisone 30 mg per day or more, or equivalent, for at least one month)
• formal indication for corticosteroids (eg Addison disease, status asthmaticus)
• already on corticosteroids for 2 days or more in the management of the current episode
• acute lung injury not related to viral pneumonia
• presence of H1N1 related acute myocarditis or encephalitis
• receiving antiviral treatment for more than 5 days

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 15 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France

Administrative Information

• NCT Number: NCT01014364
• Other Study ID Numbers: PCR09006
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Djillali Annane, University of Versailles
• Study Sponsor: University of Versailles
• Collaborators: Assistance Publique - Hôpitaux de Paris

Investigators

• Study Chair: Djillali Annane, MD,PhD; AP--HP and University of Versailles SQY
• Principal Investigator: Christian Brun Buisson, MD; AP-HP and Paris XII University
• Principal Investigator: Charles Mayaud; AP-HP and University of Paris VII
• Principal Investigator: Bernard Régnier; AP-HP and Paris VII University
• Principal Investigator: Christian Perronne; AP-HP and University of Versailles SQY

• PRS Account: University of Versailles
• Verification Date: December 2014