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

{ 'indexed': {'date-parts': [[2023, 1, 31]], 'date-time': '2023-01-31T06:13:56Z', 'timestamp': 1675145636995}, 'reference-count': 45, 'publisher': 'Public Library of Science (PLoS)', 'issue': '1', 'license': [ { 'start': { 'date-parts': [[2023, 1, 30]], 'date-time': '2023-01-30T00:00:00Z', 'timestamp': 1675036800000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'http://creativecommons.org/licenses/by/4.0/'}], 'funder': [ {'DOI': '10.13039/100001003', 'name': 'Boehringer Ingelheim', 'doi-asserted-by': 'publisher'}, { 'DOI': '10.13039/100000002', 'name': 'National Institutes of Health', 'doi-asserted-by': 'publisher', 'award': ['UL1TR003017']}, { 'DOI': '10.13039/100000002', 'name': 'National Institutes of Health', 'doi-asserted-by': 'publisher', 'award': ['NS065957 and NS103740']}], 'content-domain': {'domain': ['www.plosone.org'], 'crossmark-restriction': False}, 'abstract': '<jats:sec id="sec001">\n' '<jats:title>Background</jats:title>\n' '<jats:p>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 <jats:italic>Aggrenox</jats:italic> in hospitalized COVID-19 ' 'patients.</jats:p>\n' '</jats:sec>\n' '<jats:sec id="sec002">\n' '<jats:title>Methods</jats:title>\n' '<jats:p>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.</jats:p>\n' '</jats:sec>\n' '<jats:sec id="sec003">\n' '<jats:title>Results</jats:title>\n' '<jats:p>From October 1, 2020 to April 30, 2021, a total of 98 patients, who had a median ' '[IQR] age of 57 [47, 62] years and were 53.1% (n = 52) female, were randomized equally ' 'between study groups (n = 49 Aggrenox plus standard of care versus n = 49 standard of care ' 'alone). No clinically significant differences were found between those who received ' 'adjunctive Aggrenox and the control group in terms of illness severity (COVID ordinal scale) ' 'at days 14 and 28. The overall mortality through day 28 was 6.1% (3 patients, n = 49) in the ' 'Aggrenox group and 10.2% (5 patients, n = 49) in the control group (OR [95% CI]: 0.40 [0.04, ' '4.01], p = 0.44). Respiratory failure through day 28 occurred in 4 (8.3%, n = 48) patients in ' 'the Aggrenox group and 7 (14.6%, n = 48) patients in the standard of care group (OR [95% CI]: ' '0.21 [0.02, 2.56], p = 0.22). A larger decrease in the platelet count and blood glucose ' 'levels, and larger increase in creatinine and sodium levels within the first 7 days of ' 'hospital admission were each independent predictors of 28-day mortality (p &lt; ' '0.05).</jats:p>\n' '</jats:sec>\n' '<jats:sec id="sec004">\n' '<jats:title>Conclusion</jats:title>\n' '<jats:p>In this study of hospitalized patients with COVID-19, while the outcomes of COVID ' 'illness severity, odds of mortality, and chance of respiratory failure were better in the ' 'Aggrenox group compared to standard of care alone, the data did not reach statistical ' 'significance to support the standard use of adjuvant Aggrenox in such patients.</jats:p>\n' '</jats:sec>', 'DOI': '10.1371/journal.pone.0274243', 'type': 'journal-article', 'created': {'date-parts': [[2023, 1, 30]], 'date-time': '2023-01-30T19:36:19Z', 'timestamp': 1675107379000}, 'page': 'e0274243', 'update-policy': 'http://dx.doi.org/10.1371/journal.pone.corrections_policy', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'A randomized controlled trial to evaluate outcomes with Aggrenox in patients with SARS-CoV-2 ' 'infection', 'prefix': '10.1371', 'volume': '18', 'author': [ { 'ORCID': 'http://orcid.org/0000-0002-4162-4691', 'authenticated-orcid': True, 'given': 'Amit', 'family': 'Singla', 'sequence': 'first', 'affiliation': []}, {'given': 'Nicholas B.', 'family': 'Dadario', 'sequence': 'additional', 'affiliation': []}, {'given': 'Ashima', 'family': 'Singla', 'sequence': 'additional', 'affiliation': []}, {'given': 'Patricia', 'family': 'Greenberg', 'sequence': 'additional', 'affiliation': []}, {'given': 'Rachel', 'family': 'Yan', 'sequence': 'additional', 'affiliation': []}, {'given': 'Anil', 'family': 'Nanda', 'sequence': 'additional', 'affiliation': []}, {'given': 'Detlev', 'family': 'Boison', 'sequence': 'additional', 'affiliation': []}, {'given': 'Rakesh', 'family': 'Malhotra', 'sequence': 'additional', 'affiliation': []}, {'given': 'Sunil', 'family': 'Patel', 'sequence': 'additional', 'affiliation': []}, {'given': 'Suri', 'family': 'Nipun', 'sequence': 'additional', 'affiliation': []}, {'given': 'Kaur', 'family': 'Maninderpal', 'sequence': 'additional', 'affiliation': []}, {'given': 'Dorothy', 'family': 'Castro', 'sequence': 'additional', 'affiliation': []}, {'given': 'Sanaa', 'family': 'Bdiiwi', 'sequence': 'additional', 'affiliation': []}, {'given': 'Hala', 'family': 'Boktor', 'sequence': 'additional', 'affiliation': []}, {'given': 'Htay Htay', 'family': 'Kyi', 'sequence': 'additional', 'affiliation': []}, {'given': 'Anne', 'family': 'Sutherland', 'sequence': 'additional', 'affiliation': []}, {'given': 'Amee', 'family': 'Patrawalla', 'sequence': 'additional', 'affiliation': []}, {'given': 'Kevin', 'family': 'Ly', 'sequence': 'additional', 'affiliation': []}, {'given': 'Yingda', 'family': 'Xie', 'sequence': 'additional', 'affiliation': []}, {'given': 'Ashish', 'family': 'Sonig', 'sequence': 'additional', 'affiliation': []}, {'given': 'Priyank', 'family': 'Khandelwal', 'sequence': 'additional', 'affiliation': []}, {'given': 'James', 'family': 'Liu', 'sequence': 'additional', 'affiliation': []}, {'given': 'Joseph', 'family': 'Koziol', 'sequence': 'additional', 'affiliation': []}, {'given': 'Diana', 'family': 'Finkle', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0003-1222-9980', 'authenticated-orcid': True, 'given': 'Sara', 'family': 'Subanna', 'sequence': 'additional', 'affiliation': []}, {'given': 'Steven K.', 'family': 'Libutti', 'sequence': 'additional', 'affiliation': []}], 'member': '340', 'published-online': {'date-parts': [[2023, 1, 30]]}, 'reference': [ { 'key': 'pone.0274243.ref001', 'unstructured': 'WHO. 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