Skip to content

Clinical Trial Design to Test Isosorbide Dinitrate as an Anti-Viral Treatment for COVID-19

March 8, 2021

Poster Presentation at the American Society of Clinical Pharmacology and Therapeutics March 8 — March 17, 2021

Deployed service members are at risk now and in the future to current and new coronavirus strains. This is evident by outbreaks onboard the USS Theodore Roosevelt, USS San Diego, and USS Philippine Sea. Better treatments to prevent mortality are needed should vaccines be ineffective against new coronavirus strains. The following abstract and poster on isosorbide dinitrate as a repurposed drug addresses this need. is promoting future trials of isosorbide dinitrate as a COVID-19 treatment through various efforts. Partners are invited to join in this endeavor. Contact

To view an enlarged poster version, click on the poster overlay below:

Copyright 2021 Thomas R. Roesel

The following abstract for this poster has been published in Clinical Pharmacology and Therapeutics. The citation should read: Roesel, T. Clinical Trial Design to Test Isosorbide Dinitrate as an Anti-Viral Treatment for COVID-19. Clinical Pharmacology and Therapeutics 2021, 109 (S1):47. It can be found at by scrolling halfway down the list of posters. It is identified as poster PIII-009 and reads as follows:


T. Roesel;, Bozman, MD, USA.

BACKGROUND: COVID-19 is characterized by pulmonary disease that can lead to death. In the RECOVERY trial (1), those infected and intubated who received dexamethasone (DXM) for 3 to 10-days (6 mg/day), had an improved 28-day mortality of 29.3% vs. 41.4% for control (RR of 0.64, 95% CI 0.51 to 0.81). lists several COVID randomized clinical trials (RCTs) testing nitric oxide (NO) gas, but none use NO donor isosorbide dinitrate (ISDN). Since ISDN antiviral activity was shown in vitro and in Coxsackie B3 virus (CVB3) infected mice (2), an RCT using ISDN vs. placebo is proposed for intubated COVID patients who receive 10-days of DXM concomitantly.

METHODS: Log-rank analysis determined sample size for RCT feasibility. Accrual time was 240 days with 90-day follow-up. Placebo to drug allocation was 1:1. Power was 0.85, and type I error was 0.05. A calculated median survival time for those intubated and on DXM was derived from the RECOVERY trial. The RR ratio of 0.85 was deemed significant. All subjects would receive 10days of DXM with either 10days of placebo or IDSN.

RESULTS: Calculations reveal that an RCT with a 28 day mortality end-point requires 1492 patients, divided between 746 experimental subjects and 746 controls.

CONCLUSION: An RCT pitting repurposed ISDN against placebo to treat COVID is feasible. A positive ISDN RCT in DXM-treated COVID patients would then warrant evaluation in non-intubated patients. ISDN enhances O2-release from oxyhemoglobin in vitro under low O2, a possible benefit for hypoxic patients. Others postulate that NO inactivates the catalytic cysteine 147 residue of the CVB3 3C protease as the mechanism of antiviral ISDN action. Based on catalytic site homology between the SARS-CoV-2 3CLpro (Mpro) and CVB3 3C protease, one could infer a shared mechanism.

1. The RECOVERY Collaborative Group. Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report. New England Journal of Medicine 2020. doi: 10.1056/NEJMoa2021436.

2. Zell, R., et al. Nitric oxide donors inhibit the Coxsackievirus B3 proteinases 2A and 3C in vitro, virus production in cells, and signs of myocarditis in virus-infected mice. Med. Microbiol. Immunol. 193, 91:100 (2004).

From → Posts

Leave a Comment

Leave a Reply

%d bloggers like this: