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

A

Assistance Publique - Hôpitaux de Paris

Status and phase

Terminated
Phase 3

Conditions

COVID-19

Treatments

Drug: 2: Standard of care
Drug: 1: Naproxen

Study type

Interventional

Funder types

Other

Identifiers

NCT04325633
APHP200387

Details and patient eligibility

About

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.

Full 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.

Enrollment

30 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

30 participants in 2 patient groups, including a placebo group

1: Naproxen
Experimental group
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)
Treatment:
Drug: 2: Standard of care
Drug: 1: Naproxen
2: Standard of care
Placebo Comparator group
Description:
Standard of care
Treatment:
Drug: 2: Standard of care

Trial contacts and locations

2

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Data sourced from clinicaltrials.gov

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