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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04325633
Recruitment Status : Not yet recruiting
First Posted : March 27, 2020
Last Update Posted : April 14, 2020
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

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.

Condition or disease Intervention/treatment Phase
COVID-19 Drug: 1: Naproxen Drug: 2: Standard of care Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 584 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Efficacy of Addition of Naproxen in the Treatment of Critically Ill Patients Hospitalized for COVID-19 Infection
Estimated Study Start Date : April 13, 2020
Estimated Primary Completion Date : May 13, 2021
Estimated Study Completion Date : July 13, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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)
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

Placebo Comparator: 2: Standard of care
Standard of care
Drug: 2: Standard of care
Standard of care




Primary Outcome Measures :
  1. Mortality all causes at day30 [ Time Frame: at day30 ]

Secondary Outcome Measures :
  1. Number of days alive free of mechanical ventilation [ Time Frame: during 30 days after randomization ]
  2. Number of days alive outside [ Time Frame: during 30 days after randomization ]
  3. Number of days alive outside hospital [ Time Frame: during 30 days after randomization ]
  4. Maximal changes in Sofa score [ Time Frame: in the first 7 days after randomization ]
  5. Time to negativation of virus titer in the nasopharyngeal aspirate (NPA) [ Time Frame: during 90 days after randomization ]


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:

  • 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

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): NCT04325633


Contacts
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Contact: Frédéric ADNET, MD, PhD +33 1-48-96-44-08 frederic.adnet@aphp.fr
Contact: Anny SLAMA SCHWOK, MD anny.slama-schwok@inserm.fr

Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
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Principal Investigator: Frédéric ADNET, MD, PhD Assistance Publique - Hôpitaux de Paris
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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT04325633    
Other Study ID Numbers: APHP200387
First Posted: March 27, 2020    Key Record Dates
Last Update Posted: April 14, 2020
Last Verified: April 2020

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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 Assistance Publique - Hôpitaux de Paris:
COVID-19
SARS-COV-2
Naproxen
Nonsteroidal anti-inflamatory drug
Additional relevant MeSH terms:
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Critical Illness
Disease Attributes
Pathologic Processes
Naproxen
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Gout Suppressants
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action