NCT04383899: RISC

Role of Ibuprofen and Other Medicines on Severity of Coronavirus Disease 2019

Withdrawn Last updated 25 February 2021

What this trial tests

trial testing Questionnaire in Coronavirus Infection. Withdrawn.

Timeline

30 September 2020

Primary endpoint
31 October 2020

30 November 2020

Quick facts

Lead sponsor	University Hospital, Bordeaux
Status	Withdrawn
Study type	OBSERVATIONAL
Start date	30 September 2020
Primary completion	31 October 2020
Estimated completion	30 November 2020

Drugs / interventions tested

• Questionnaire

Conditions studied

• Coronavirus Infection — all drugs for Coronavirus Infection →

Sponsor

University Hospital, Bordeaux

Who can join

Eligibility, any sex, with Coronavirus Infection. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

It has been suggested that ibuprofen might be associated with more severe cases of coronavirus infections, based on the observation that severe COVID cases had been exposed to ibuprofen, resulting in a warning by the French authorities.

This was attributed to:

1. a suggestion that ibuprofen might upregulate ACE-2 thereby increasing the entrance of COVID-19 into the cells,
2. an analogy with bacterial soft-tissue infections where more severe infections on NSAIDs are attributed to an immune-depressive action of NSAIDs, or to belated treatment because of initial symptom suppression,
3. fever is a natural response to viral infection, and reduces virus activity: antipyretic activity might reduce natural defenses against viruses. However fever reduction in critically ill patients had no effect on survival.

However, these assertions are unclear: upregulation of ACEII would increase the risk of infection, not necessarily its severity, and would only apply to the use of NSAIDs before the infection, i.e. chronic exposure. It would be irrelevant to the infection once the patients are infected, i.e., to symptomatic treatment of COVID-19 infection.

Anti-inflammatory effect masking the early symptoms of bacterial infections resulting in later antibiotic or other treatment is not applicable: there is no treatment of the virus that might be affected by masking symptoms.

Antipyretic effect increasing the risk or the severity of infection would apply equally to all antipyretic agents including paracetamol, which share the same mechanism of action for fever reduction.

EMA remains prudent about this assertion

In addition, excess reliance on paracetamol while discouraging the use of ibuprofen might increase the risk of hepatic injury from paracetamol overdose. Paracetamol is the prime drug associated with liver injury and transplantation, in voluntary and inadvertent overdose or even at normal doses. This might be increased by COVID-related liver function alterations.

It is therefore proposed to conduct a case-control study in a cohort of patients admitted to hospital in France with COVID-19 infection.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Does Ibuprofen Worsen COVID-19?
   Moore N, Carleton B, Blin P, Bosco-Levy P, et al · · 2020 · cited 51× · PMID 32529474 · DOI 10.1007/s40264-020-00953-0
2. Should ACE2 be given a chance in COVID-19 therapeutics: A semi-systematic review of strategies enhancing ACE2.
   Kaur U, Acharya K, Mondal R, Singh A, et al · · 2020 · cited 30× · PMID 32926917 · DOI 10.1016/j.ejphar.2020.173545
3. DrugWAS: Drug-wide Association Studies for COVID-19 Drug Repurposing.
   Bejan CA, Cahill KN, Staso PJ, Choi L, et al · · 2021 · cited 20× · PMID 34314511 · DOI 10.1002/cpt.2376
4. Inflammation, immunity and potential target therapy of SARS-COV-2: A total scale analysis review.
   Smail SW, Saeed M, Twana Alkasalias, Khudhur ZO, et al · · 2021 · cited 20× · PMID 33640537 · DOI 10.1016/j.fct.2021.112087
5. Challenges and Opportunities from Targeting Inflammatory Responses to SARS-CoV-2 Infection: A Narrative Review.
   Lariccia V, Magi S, Serfilippi T, Toujani M, et al · · 2020 · cited 19× · PMID 33322733 · DOI 10.3390/jcm9124021
6. COVID-19 and Headache Medicine: A Narrative Review of Non-Steroidal Anti-Inflammatory Drug (NSAID) and Corticosteroid Use.
   Arca KN, Smith JH, Chiang CC, Starling AJ, et al · · 2020 · cited 16× · PMID 32648592 · DOI 10.1111/head.13903
7. Crosstalk between hypoxic cellular micro-environment and the immune system: a potential therapeutic target for infectious diseases.
   Akinsulie OC, Shahzad S, Ogunleye SC, Oladapo IP, et al · · 2023 · cited 11× · PMID 37600803 · DOI 10.3389/fimmu.2023.1224102
8. DrugWAS: Leveraging drug-wide association studies to facilitate drug repurposing for COVID-19
   Bejan CA, Cahill KN, Staso PJ, Choi L, et al · · 2021 · DOI 10.1101/2021.02.04.21251169