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A randomized controlled trial to evaluate outcomes with Aggrenox in patients with SARS-CoV-2 infection

Singla et al., PLOS ONE, doi:10.1371/journal.pone.0274243, NCT04410328

Jan 2023

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Aspirin for COVID-19

24th treatment shown to reduce risk in August 2021

^*, now known with p = 0.000087 from 73 studies, recognized in 2 countries.

Lower risk for mortality and progression.

No treatment is 100% effective. Protocols combine complementary and synergistic treatments. ^* >10% efficacy in meta analysis with ≥3 clinical studies.

4,000+ studies for 60+ treatments. c19early.org

RCT 98 hospitalized patients in the USA, 49 treated with aspirin and dipyridamole, showing improved results with treatment, but without statistical significance.

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risk of death, 57.4% lower, RR 0.43, p = 0.44, treatment 3 of 49 (6.1%), control 5 of 49 (10.2%), adjusted per study, odds ratio converted to relative risk, multivariable, day 28.

risk of death, 15.0% lower, OR 0.85, p = 0.87, treatment 49, control 49, adjusted per study, multivariable, day 14, RR approximated with OR.

risk of mechanical ventilation, 20.0% lower, RR 0.80, p = 1.00, treatment 4 of 49 (8.2%), control 5 of 49 (10.2%), NNT 49.

risk of ICU admission, 28.6% lower, RR 0.71, p = 0.76, treatment 5 of 49 (10.2%), control 7 of 49 (14.3%), NNT 25.

risk of progression, 33.3% lower, RR 0.67, p = 0.74, treatment 4 of 49 (8.2%), control 6 of 49 (12.2%), NNT 24, day 28.

risk of progression, 76.3% lower, RR 0.24, p = 0.22, treatment 4 of 49 (8.2%), control 7 of 49 (14.3%), odds ratio converted to relative risk, respiratory failure, day 28.

risk of progression, 44.4% lower, RR 0.56, p = 0.39, treatment 5 of 49 (10.2%), control 9 of 49 (18.4%), NNT 12, AKI.

risk of progression, 85.7% lower, RR 0.14, p = 0.24, treatment 0 of 49 (0.0%), control 3 of 49 (6.1%), NNT 16, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), DIC.

risk of progression, 25.0% lower, RR 0.75, p = 0.62, treatment 9 of 49 (18.4%), control 12 of 49 (24.5%), NNT 16, liver dysfunction.

Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates

Singla et al., 30 Jan 2023, Randomized Controlled Trial, USA, peer-reviewed, 26 authors, study period 1 October, 2020 - 30 April, 2021, this trial uses multiple treatments in the treatment arm (combined with dipyridamole) - results of individual treatments may vary, trial NCT04410328 (history). Contact: as3321@njms.rutgers.edu.

This Paper Aspirin All

A randomized controlled trial to evaluate outcomes with Aggrenox in patients with SARS-CoV-2 infection

Amit Singla, Nicholas B Dadario, Ashima Singla, Patricia Greenberg, Rachel Yan, Anil Nanda, Detlev Boison, Rakesh Malhotra, Sunil Patel, Suri Nipun, Kaur Maninderpal, Dorothy Castro, Sanaa Bdiiwi, Hala Boktor, Htay Htay Kyi, Anne Sutherland, Amee Patrawalla, Kevin Ly, Yingda Xie, Ashish Sonig, Priyank Khandelwal, James Liu, Joseph Koziol, Diana Finkle, Sara Subanna, Steven K Libutti

PLOS ONE, doi:10.1371/journal.pone.0274243

Background Coronavirus disease 2019 (COVID-19) is an immunoinflammatory and hypercoagulable state that contributes to respiratory distress, multi-organ dysfunction, and mortality. Dipyridamole, by increasing extracellular adenosine, has been postulated to be protective for COVID-19 patients through its immunosuppressive, anti-inflammatory, anti-coagulant, vasodilatory, and anti-viral actions. Likewise, low-dose aspirin has also demonstrated protective effects for COVID-19 patients. This study evaluated the effect of these two drugs formulated together as Aggrenox in hospitalized COVID-19 patients. Methods In an open-label, single site randomized controlled trial (RCT), hospitalized COVID-19 patients were assigned to adjunctive Aggrenox (Dipyridamole ER 200mg/ Aspirin 25mg orally/enterally) with standard of care treatment compared to standard of care treatment alone. Primary endpoint was illness severity according to changes on the eight-point COVID ordinal scale, with levels of 1 to 8 where higher scores represent worse illness. Secondary endpoints included all-cause mortality and respiratory failure. Outcomes were measured through days 14, 28, and/or hospital discharge.

Supporting information S1 File. (DOCX) S2 File. (PDF) Author Contributions Conceptualization: Amit Singla, Nicholas B. Dadario, Ashima Singla, Detlev Boison, Rakesh Malhotra, Yingda Xie, Steven K. Libutti. Data curation: Amit Singla, Nicholas B. Dadario, Patricia Greenberg, Rachel Yan, Detlev Boison, Sunil Patel, Suri Nipun, Kaur Maninderpal, Dorothy Castro, Sanaa Bdiiwi, Hala Boktor, Htay Htay Kyi, Anne Sutherland, Amee Patrawalla, Kevin Ly, Yingda Xie, Priyank Khandelwal, James Liu, Sara Subanna. Formal analysis: Amit Singla, Nicholas B. Dadario, Patricia Greenberg. Methodology: Amit Singla, Patricia Greenberg, Detlev Boison. Project administration: Amit Singla, Anil Nanda, Sunil Patel, Anne Sutherland, Steven K. Libutti. Resources: Amit Singla, Anil Nanda, Yingda Xie, Ashish Sonig, James Liu, Joseph Koziol, Diana Finkle, Steven K. Libutti. Software: Amit Singla, Patricia Greenberg. Supervision: Amit Singla, Anne Sutherland, Steven K. Libutti. Validation: Amit Singla, Patricia Greenberg, Ashish Sonig. Visualization: Amit Singla, Sunil Patel, Kaur Maninderpal. Writing -original draft: Amit Singla, Nicholas B. Dadario, Ashima Singla, Patricia Greenberg. Writing -review & editing: Amit Singla, Nicholas B. Dadario, Ashima Singla, Patricia Greenberg, Rachel Yan, Anil Nanda, Detlev Boison, Rakesh Malhotra, Sunil Patel, Suri Nipun, Kaur Maninderpal, Dorothy Castro, Sanaa Bdiiwi, Hala Boktor, Htay Htay Kyi, Anne Sutherland, Amee Patrawalla, Kevin Ly, Yingda Xie, Ashish..

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Late treatment
is less effective

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