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All Studies   Meta Analysis    Recent:   
0 0.5 1 1.5 2+ SHOKS-COVID score 11% Improvement Relative Risk PCR+ on day 10 or hospita.. 39% Hospitalization time 8% Viral clearance 87% Bromhexine  Mareev et al.  LATE TREATMENT  RCT Is late treatment with bromhexine + spironolactone beneficial for COVID-19? RCT 66 patients in Russia Improved recovery (p=0.47) and viral clearance (p=0.077), not sig. c19early.org Mareev et al., Кардиология, December 2020 Favors bromhexine Favors control

Results of Open-Label non-Randomized Comparative Clinical Trial: “BromhexIne and Spironolactone for CoronаvirUs Infection requiring hospiTalization (BISCUIT)

Mareev et al., Кардиология, doi:10.18087/cardio.2020.11.n1440, NCT04424134
Dec 2020  
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Prospective 103 PCR+ patients in Russia, 33 treated with bromexhine+spironolactone, showing lower PCR+ at day 10 or hospitalization >10 days with treatment. Bromhexine 8mg 4 times daily, spironolactone 25-50 mg/day for 10 days.
Bromhexine efficacy may vary depending on the degree of TMPRSS-dependent fusion for different variants Peacock, Willett.
Study covers bromhexine and spironolactone.
relative SHOKS-COVID score, 11.3% better, RR 0.89, p = 0.47, treatment mean 2.12 (±1.39) n=33, control mean 2.39 (±1.59) n=33.
risk of PCR+ on day 10 or hospitalization >10 days, 38.8% lower, RR 0.61, p = 0.02, treatment 14 of 24 (58.3%), control 20 of 21 (95.2%), NNT 2.7, odds ratio converted to relative risk.
hospitalization time, 8.2% lower, relative time 0.92, p = 0.35, treatment 33, control 33.
risk of no viral clearance, 87.4% lower, RR 0.13, p = 0.08, treatment 0 of 17 (0.0%), control 3 of 13 (23.1%), NNT 4.3, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), day 10.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Mareev et al., 3 Dec 2020, Randomized Controlled Trial, Russia, peer-reviewed, 20 authors, this trial uses multiple treatments in the treatment arm (combined with spironolactone) - results of individual treatments may vary, trial NCT04424134 (history).
This PaperBromhexineAll
Abstract: § EDITORIAL ARTICLES Mareev V. Yu.1,2, Orlova Ya.A.1,2, Plisyk A.G.1,2, Pavlikova E.P.1,2, Matskeplishvili S.Т.1, Akopyan Z.A.1,2, Seredenina E. M.1,2, Potapenko A. V.1,2, Agapov M.A.1,2, Asratyan D.A.1, Dyachuk L.I.1,2, Samokhodskaya L. M.1,2, Mershina Е. А.1,2, Sinitsyn V. E.1,2, Pakhomov P. V.2, Bulanova M.M.2, Fuks A.A.2, Mareev Yu.V.3,4, Begrambekova Yu. L.1,2, Kamalov А. А.1,2 Medical Research and Educational Center of the M. V. Lomonosov Moscow State University, Moscow, Russia Faculty of Fundamental Medicine, Lomonosov Moscow State University, Russia 3 National Medical Research Centre for Therapy and Preventive Medicine Moscow, Russia 4 Robertson Centre for Biostatistics, Glasgow, Great Britain 1 2 Results of Open-Label non-Randomized Comparative Clinical Trial: “BromhexIne and Spironolactone for CoronаvirUs Infection requiring hospiTalization (BISCUIT)
{ 'DOI': '10.18087/cardio.2020.11.n1440', 'ISSN': ['2412-5660', '0022-9040'], 'URL': 'http://dx.doi.org/10.18087/cardio.2020.11.n1440', 'abstract': '<jats:p><jats:italic>Introduction</jats:italic> The aim of this study was to assess the ' 'efficacy and safety of a combination of bromhexine at a dose of 8 mg 4 times a day and ' 'spironolactone 50 mg per day in patients with mild and moderate COVID ' '19.<jats:italic>Material and methods</jats:italic> It was an open, prospective comparative ' 'non-randomized study. 103 patients were included (33 in the bromhexine and spironolactone ' 'group and 70 in the control group). All patients had a confirmed 2019 novel coronavirus ' 'infection (COVID 19) based on a positive polymerase chain reaction (PCR) for SARS-CoV-2 virus ' 'RNA and/or a typical pattern of viral pneumonia on multispiral computed tomography. The ' 'severity of lung damage was limited to stage I-II, the level of CRP should not exceed 60 mg / ' 'dL and SO2 in the air within 92-98%. The duration of treatment is 10 ' 'days.<jats:italic>Results</jats:italic> The decrease in scores on the SHOKS-COVID scale, ' 'which, in addition to assessing the clinical status, the dynamics of CRP (a marker of ' 'inflammation), D-dimer (a marker of thrombus formation), and the degree of lung damage on CT ' '(primary endpoint) was statistically significant in both groups and differences between them ' 'was not identified. Analysis for the group as a whole revealed a statistically significant ' 'reduction in hospitalization time from 10.4 to 9.0 days (by 1.5 days, p=0.033) and fever time ' 'from 6.5 to 3.9 days (by 2.5 days, p&lt;0.001). Given the incomplete balance of the groups, ' 'the main analysis included 66 patients who were match with using propensity score matching. ' 'In matched patients, temperature normalization in the bromhexine/spironolactone group ' 'occurred 2 days faster than in the control group (p=0.008). Virus elimination by the 10th day ' 'was recorded in all patients in the bromhexine/spironolactone group; the control group ' 'viremia continued in 23.3% (p=0.077). The number of patients who had a positive PCR to the ' 'SARS-CoV-2 virus on the 10th day of hospitalization or longer (≥10 days) hospitalization in ' 'the control group was 20/21 (95.2%), and in the group with bromhexine /spironolactone -14/24 ' '(58.3%), p=0.012. The odds ratio of having a positive PCR or more than ten days of ' 'hospitalization was 0.07 (95% CI: 0.008 - 0.61, p=0.0161) with bromhexine and spironolactone ' 'versus controls. No side effects were reported in the study ' 'group.<jats:italic>Conclusion</jats:italic> The combination of bromhexine with spironolactone ' 'appeared effective in treating a new coronavirus infection by achieving a faster ' 'normalization of the clinical condition, lowering the temperature one and a half times ' 'faster, and reducing explanatory combine endpoint the viral load or long duration of ' 'hospitalization (≥ 10 days).</jats:p>', 'author': [ { 'ORCID': 'http://orcid.org/0000-0002-7285-2048', 'affiliation': [ { 'name': 'Medical Research and Educational Center of the M. V. Lomonosov ' 'Moscow State University, Moscow, Russia\r\n' 'Faculty of Fundamental Medicine, Lomonosov Moscow State ' 'University, Russia'}], 'authenticated-orcid': True, 'family': 'Mareev', 'given': 'V. Yu.', 'sequence': 'first'}, { 'ORCID': 'http://orcid.org/0000-0002-8160-5612', 'affiliation': [ { 'name': 'Medical Research and Educational Center of the M. V. Lomonosov ' 'Moscow State University, Moscow, Russia\r\n' 'Faculty of Fundamental Medicine, Lomonosov Moscow State ' 'University, Russia'}], 'authenticated-orcid': True, 'family': 'Orlova', 'given': 'Ya. A.', 'sequence': 'additional'}, { 'affiliation': [ { 'name': 'Medical Research and Educational Center of the M. V. Lomonosov ' 'Moscow State University, Moscow, Russia\r\n' 'Faculty of Fundamental Medicine, Lomonosov Moscow State ' 'University, Russia'}], 'family': 'Plisyk', 'given': 'A. G.', 'sequence': 'additional'}, { 'ORCID': 'http://orcid.org/0000-0001-7693-5281', 'affiliation': [ { 'name': 'Medical Research and Educational Center of the M. V. Lomonosov ' 'Moscow State University, Moscow, Russia\r\n' 'Faculty of Fundamental Medicine, Lomonosov Moscow State ' 'University, Russia'}], 'authenticated-orcid': True, 'family': 'Pavlikova', 'given': 'E. P.', 'sequence': 'additional'}, { 'ORCID': 'http://orcid.org/0000-0002-5670-167X', 'affiliation': [ { 'name': 'Medical Research and Educational Center of the M. V. Lomonosov ' 'Moscow State University, Moscow, Russia'}], 'authenticated-orcid': True, 'family': 'Matskeplishvili', 'given': 'S. T.', 'sequence': 'additional'}, { 'affiliation': [ { 'name': 'Medical Research and Educational Center of the M. V. Lomonosov ' 'Moscow State University, Moscow, Russia\r\n' 'Faculty of Fundamental Medicine, Lomonosov Moscow State ' 'University, Russia'}], 'family': 'Akopyan', 'given': 'Z. A.', 'sequence': 'additional'}, { 'ORCID': 'http://orcid.org/0000-0002-1490-2078', 'affiliation': [ { 'name': 'Medical Research and Educational Center of the M. V. Lomonosov ' 'Moscow State University, Moscow, Russia\r\n' 'Faculty of Fundamental Medicine, Lomonosov Moscow State ' 'University, Russia'}], 'authenticated-orcid': True, 'family': 'Seredenina', 'given': 'E. M.', 'sequence': 'additional'}, { 'ORCID': 'http://orcid.org/0000-0002-9820-4276', 'affiliation': [ { 'name': 'Medical Research and Educational Center of the M. V. Lomonosov ' 'Moscow State University, Moscow, Russia\r\n' 'Faculty of Fundamental Medicine, Lomonosov Moscow State ' 'University, Russia'}], 'authenticated-orcid': True, 'family': 'Potapenko', 'given': 'A. V.', 'sequence': 'additional'}, { 'affiliation': [ { 'name': 'Medical Research and Educational Center of the M. V. Lomonosov ' 'Moscow State University, Moscow, Russia\r\n' 'Faculty of Fundamental Medicine, Lomonosov Moscow State ' 'University, Russia'}], 'family': 'Agapov', 'given': 'M. A.', 'sequence': 'additional'}, { 'ORCID': 'http://orcid.org/0000-0002-1939-7189', 'affiliation': [ { 'name': 'Medical Research and Educational Center of the M. V. Lomonosov ' 'Moscow State University, Moscow, Russia'}], 'authenticated-orcid': True, 'family': 'Asratyan', 'given': 'D. A.', 'sequence': 'additional'}, { 'affiliation': [ { 'name': 'Medical Research and Educational Center of the M. V. Lomonosov ' 'Moscow State University, Moscow, Russia\r\n' 'Faculty of Fundamental Medicine, Lomonosov Moscow State ' 'University, Russia'}], 'family': 'Dyachuk', 'given': 'L. I.', 'sequence': 'additional'}, { 'ORCID': 'http://orcid.org/0000-0001-6734-3989', 'affiliation': [ { 'name': 'Medical Research and Educational Center of the M. V. Lomonosov ' 'Moscow State University, Moscow, Russia\r\n' 'Faculty of Fundamental Medicine, Lomonosov Moscow State ' 'University, Russia'}], 'authenticated-orcid': True, 'family': 'Samokhodskaya', 'given': 'L. M.', 'sequence': 'additional'}, { 'ORCID': 'http://orcid.org/0000-0002-1266-4926', 'affiliation': [ { 'name': 'Medical Research and Educational Center of the M. V. Lomonosov ' 'Moscow State University, Moscow, Russia\r\n' 'Faculty of Fundamental Medicine, Lomonosov Moscow State ' 'University, Russia'}], 'authenticated-orcid': True, 'family': 'Mershina', 'given': 'Е. А.', 'sequence': 'additional'}, { 'ORCID': 'http://orcid.org/0000-0002-5649-2193', 'affiliation': [ { 'name': 'Medical Research and Educational Center of the M. V. Lomonosov ' 'Moscow State University, Moscow, Russia\r\n' 'Faculty of Fundamental Medicine, Lomonosov Moscow State ' 'University, Russia'}], 'authenticated-orcid': True, 'family': 'Sinitsyn', 'given': 'V. E.', 'sequence': 'additional'}, { 'affiliation': [ { 'name': 'Faculty of Fundamental Medicine, Lomonosov Moscow State ' 'University, Russia'}], 'family': 'Pakhomov', 'given': 'P. V.', 'sequence': 'additional'}, { 'affiliation': [ { 'name': 'Faculty of Fundamental Medicine, Lomonosov Moscow State ' 'University, Russia'}], 'family': 'Bulanova', 'given': 'M. M.', 'sequence': 'additional'}, { 'affiliation': [ { 'name': 'Faculty of Fundamental Medicine, Lomonosov Moscow State ' 'University, Russia'}], 'family': 'Fuks', 'given': 'A. A.', 'sequence': 'additional'}, { 'ORCID': 'http://orcid.org/0000-0002-1939-7189', 'affiliation': [ { 'name': 'National Medical Research Centre for Therapy and Preventive ' 'Medicine, Moscow, Russia\r\n' 'Robertson Centre for Biostatistics, Glasgow, Great Britain'}], 'authenticated-orcid': True, 'family': 'Mareev', 'given': 'Yu. V.', 'sequence': 'additional'}, { 'ORCID': 'http://orcid.org/0000-0001-7992-6081', 'affiliation': [ { 'name': 'Medical Research and Educational Center of the M. V. Lomonosov ' 'Moscow State University, Moscow, Russia\r\n' 'Faculty of Fundamental Medicine, Lomonosov Moscow State ' 'University, Russia'}], 'authenticated-orcid': True, 'family': 'Begrambekova', 'given': 'Yu. 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Late treatment
is less effective
Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
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