Efficacy of Addition of Naproxen in the Treatment of Critically Ill Patients Hospitalized for COVID-19 Infection (ENACOVID)
Primary Purpose
COVID-19
Status
Terminated
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
1: Naproxen
2: Standard of care
Sponsored by
About this trial
This is an interventional treatment trial for COVID-19 focused on measuring COVID-19, SARS-COV-2, Naproxen, Nonsteroidal anti-inflamatory drug
Eligibility 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
Sites / Locations
- Réanimation médico-chirurgicale, Avicenne Hospital
- Urgences, Avicenne Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
1: Naproxen
2: Standard of care
Arm 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)
Standard of care
Outcomes
Primary Outcome Measures
Mortality all causes at day30
Secondary Outcome Measures
Number of days alive free of mechanical ventilation
Number of days alive outside
Number of days alive outside hospital
Maximal changes in Sofa score
Time to negativation of virus titer in the nasopharyngeal aspirate (NPA)
Full Information
NCT ID
NCT04325633
First Posted
March 26, 2020
Last Updated
February 24, 2021
Sponsor
Assistance Publique - Hôpitaux de Paris
1. Study Identification
Unique Protocol Identification Number
NCT04325633
Brief Title
Efficacy of Addition of Naproxen in the Treatment of Critically Ill Patients Hospitalized for COVID-19 Infection
Acronym
ENACOVID
Official Title
Efficacy of Addition of Naproxen in the Treatment of Critically Ill Patients Hospitalized for COVID-19 Infection
Study Type
Interventional
2. Study Status
Record Verification Date
February 2021
Overall Recruitment Status
Terminated
Why Stopped
Stop inclusions for insufficient recruitment
Study Start Date
April 24, 2020 (Actual)
Primary Completion Date
December 15, 2020 (Actual)
Study Completion Date
December 15, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19
Keywords
COVID-19, SARS-COV-2, Naproxen, Nonsteroidal anti-inflamatory drug
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1: Naproxen
Arm Type
Experimental
Arm 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)
Arm Title
2: Standard of care
Arm Type
Placebo Comparator
Arm Description
Standard of care
Intervention Type
Drug
Intervention Name(s)
1: Naproxen
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
2: Standard of care
Intervention Description
Standard of care
Primary Outcome Measure Information:
Title
Mortality all causes at day30
Time Frame
at day30
Secondary Outcome Measure Information:
Title
Number of days alive free of mechanical ventilation
Time Frame
during 30 days after randomization
Title
Number of days alive outside
Time Frame
during 30 days after randomization
Title
Number of days alive outside hospital
Time Frame
during 30 days after randomization
Title
Maximal changes in Sofa score
Time Frame
in the first 7 days after randomization
Title
Time to negativation of virus titer in the nasopharyngeal aspirate (NPA)
Time Frame
during 90 days after randomization
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Frédéric ADNET, MD, PhD
Organizational Affiliation
Assistance Publique - Hôpitaux de Paris
Official's Role
Principal Investigator
Facility Information:
Facility Name
Réanimation médico-chirurgicale, Avicenne Hospital
City
Bobigny
ZIP/Postal Code
93000
Country
France
Facility Name
Urgences, Avicenne Hospital
City
Bobigny
ZIP/Postal Code
93000
Country
France
12. IPD Sharing Statement
Learn more about this trial
Efficacy of Addition of Naproxen in the Treatment of Critically Ill Patients Hospitalized for COVID-19 Infection
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