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Efficacy of Addition of Naproxen in the Treatment of Critically Ill Patients Hospitalized for COVID-19 Infection (ENACOVID)

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ClinicalTrials.gov Identifier: NCT04325633
Recruitment Status : Terminated (Stop inclusions for insufficient recruitment)
First Posted : March 27, 2020
Last Update Posted : February 25, 2021
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Tracking Information
First Submitted Date  ICMJE March 26, 2020
First Posted Date  ICMJE March 27, 2020
Last Update Posted Date February 25, 2021
Actual Study Start Date  ICMJE April 24, 2020
Actual Primary Completion Date December 15, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 26, 2020)
Mortality all causes at day30 [ Time Frame: at day30 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 26, 2020)
  • Number of days alive free of mechanical ventilation [ Time Frame: during 30 days after randomization ]
  • Number of days alive outside [ Time Frame: during 30 days after randomization ]
  • Number of days alive outside hospital [ Time Frame: during 30 days after randomization ]
  • Maximal changes in Sofa score [ Time Frame: in the first 7 days after randomization ]
  • Time to negativation of virus titer in the nasopharyngeal aspirate (NPA) [ Time Frame: during 90 days after randomization ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy of Addition of Naproxen in the Treatment of Critically Ill Patients Hospitalized for COVID-19 Infection
Official Title  ICMJE Efficacy of Addition of Naproxen in the Treatment of Critically Ill Patients Hospitalized for COVID-19 Infection
Brief Summary The symptoms of respiratory distress caused by COVID-19 may be reduced by drugs combining anti-inflammatory and antiviral effects. This dual effect may simultaneously protect severely-ill patients and reduce the viral load, therefore limiting virus dissemination We want to demonstrate the superiority of naproxen (anti-inflamatory drug) treatment addition to standard of care compared to standard of care in term of 30-day mortality.
Detailed Description Coronavirus Disease 2019 (COVID-19) is due to SARS-CoV-2 infection. (1,2) The exacerbated inflammatory response in COVID-19 infected critically ill patients calls for appropriate anti inflammatory therapeutics combined with antiviral effects. Thus, drugs combining anti-inflammatory and antiviral effects may reduce the symptoms of respiratory distress caused by COVID-19. This dual effect may simultaneously protect severely ill patients and reduce the viral load, therefore limiting virus dissemination. Naproxen, an approved anti-inflammatory drug, is an inhibitor of both cyclo oxygenase (COX-2) and of Influenza A virus nucleoprotein (NP). The NP of Coronavirus (CoV), positive-sense single-stranded viruses, share with negative-sense single-stranded viruses as Influenza the ability to bind to- and protect genomic RNA by forming self-associated oligomers in a helical structure with RNA. Naproxen was shown to bind the Influenza A virus NP making electrostatic and hydrophobic interactions with conserved residues of the RNA binding groove and C terminal domain. (3) Consequently, naproxen binding competed with NP association with viral RNA and impeded the NP self-association process which strongly reduced viral transcription/replication. This drug may have the potential to present antiviral properties against SARS-CoV-2 suggested by modelling work based on the structures of CoV NP. The high sequence conservation within the coronavirus family, including severe acute respiratory syndrome (SARS-CoV) and the present SARSCoV-2 coronavirus allows to perform this comparison. (4) A recent clinical trial shown that the combination of clarithromycin, naproxen and oseltamivir reduced mortality of patients hospitalized for H3N2 Influenza infection. (5). Inappropriate inflammatory response in CODIV-19 patients was demonstrated in a recent study where Intensive Care Unit (ICU) patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNF? compared with non-ICU patients.(2) We suggest that naproxen could combine a broad-spectrum antiviral activity with its well-known anti inflammatory action that could help reducing severe respiratory mortality associated with COVID-19.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE COVID-19
Intervention  ICMJE
  • Drug: 1: Naproxen
    Description : Administration of naproxen 250 mg twice and lansoprazole 30 mg daily for prevention of gastropathy induced by stress or a nonsteroidal anti-inflammatory drug (NSAID) in addition to standard of care (SOC)
  • Drug: 2: Standard of care
    Standard of care
Study Arms  ICMJE
  • Experimental: 1: Naproxen
    Administration of naproxen 250 mg twice and lansoprazole 30 mg daily for prevention of gastropathy induced by stress or a nonsteroidal anti-inflammatory drug (NSAID) in addition to standard of care (SOC)
    Interventions:
    • Drug: 1: Naproxen
    • Drug: 2: Standard of care
  • Placebo Comparator: 2: Standard of care
    Standard of care
    Intervention: Drug: 2: Standard of care
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: February 24, 2021)
30
Original Estimated Enrollment  ICMJE
 (submitted: March 26, 2020)
584
Actual Study Completion Date  ICMJE December 15, 2020
Actual Primary Completion Date December 15, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • COVID-19 infected patient
  • Age 18 years or older
  • Presence of pneumonia
  • PaO2/FiO2 < 300 mm Hg or SpO2 < 93% in air ambient or need to supplementary oxygen administration in order to maintain SpO2 range in [94-98%] or lung infiltrates > 50%
  • Medical insurance

Exclusion Criteria:

  • Presence of do-not-resuscitate order
  • Pregnancy
  • Prisoners
  • Known Naproxen allergy or intolerance
  • Severe renal failure
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04325633
Other Study ID Numbers  ICMJE APHP200387
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Assistance Publique - Hôpitaux de Paris
Study Sponsor  ICMJE Assistance Publique - Hôpitaux de Paris
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Frédéric ADNET, MD, PhD Assistance Publique - Hôpitaux de Paris
PRS Account Assistance Publique - Hôpitaux de Paris
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP