An Outpatient Clinical Trial Using Ivermectin and Doxycycline in COVID-19 Positive Patients at High Risk to Prevent COVID-19 Related Hospitalization

Summary

The purpose of this Clinical trial is to explore the therapeutic benefits of Ivermectin and Doxycycline in different combinations in high risk patients diagnosed with COVID-19.

Timeline

Start

2020-12-28

Primary completion

2021-12-28

Completion

2022-03-28

Publications

• Background [1] World Health Organization. Novel Coronavirus-China [cited 2020 January 12]. https://www.who.int/csr/don/12-january-2020-novel-coronavirus-chinaExternal Link
• Background [2] Interim U.S. Guidance for Risk Assessment and Public Health Management of Persons with Potential Coronavirus Disease 2019 (COVID-19) Exposures: Geographic Risk and Contacts of Laboratory-confirmed Cases. www.cdc.gov/coronavirus/2019-ncov/php/risk-assessment.
• Background Holshue ML, DeBolt C, Lindquist S, Lofy KH, Wiesman J, Bruce H, Spitters C, Ericson K, Wilkerson S, Tural A, Diaz G, Cohn A, Fox L, Patel A, Gerber SI, Kim L, Tong S, Lu X, Lindstrom S, Pallansch MA, Weldon WC, Biggs HM, Uyeki TM, Pillai SK; Washington State 2019-nCoV Case Investigation Team. First Case of 2019 Novel Coronavirus in the United States. N Engl J Med. 2020 Mar 5;382(10):929-936. doi: 10.1056/NEJMoa2001191. Epub 2020 Jan 31.
• Background Fauci AS, Lane HC, Redfield RR. Covid-19 - Navigating the Uncharted. N Engl J Med. 2020 Mar 26;382(13):1268-1269. doi: 10.1056/NEJMe2002387. Epub 2020 Feb 28. No abstract available.
• Background [5] The RECOVERY trial in COVID-19 has provided initial results of the dexamethasone arm https://www.recoverytrial.net/files/recovery_dexamethasone_statement_160620_final.pdf
• Background [6] U.S. Food and Drug Administration. FDA cautions against the use of hydroxychloroquine or chloroquine for COVID-19 outside of the hospital setting or a clinical trial due to the risk of heart rhythm problems. Available at: https://www.fda.gov/drugs/drug-safety-and-availability/fda-cautions-against-use-hydroxychloroquine-or-chloroquine-covid-19-outside-hospital-setting-or (Accessed on April 24, 2020).
• Background [7] Georgi Momekov & Denitsa Momekova (2020) Ivermectin as a potential COVID-19 treatment from the pharmacokinetic point of view: antiviral levels are not likely attainable with known dosing regimens, Biotechnology & Biotechnological Equipment, 34:1, 469-474, DOI: 10.1080/13102818.2020.1775118
• Background [8] ICON (Ivermectin in COvid Nineteen) study: Use of Ivermectin is Associated with Lower Mortality in Hospitalized Patients with COVID19 Juliana CepelowiczRajter, M.D. 1 Michael S. Sherman, M.D.2NaazFatteh, M.D. 1 Fabio Vogel, Pharm. D., BCPS1 Jamie Sacks, Pharm. D. 1 Jean-Jacques Rajter, M.D.1,3 1. Broward Health Medical Center, Fort Lauderdale, FL 2. Emeritus Professor, Drexel University College of Medicine 3. Assistant Professor, Florida International University Corresponding author: Jean-Jacques Rajter, MD [email protected]
• Background [9] The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro, Leon Calya, Julian D. Drucea, Mike G. Cattona, David A. Jans, Kylie M. Wagstaffb,∗ a Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital, At the Peter Doherty Institute for Infection and Immunity, Victoria, 3000, Australia b Biomedicine Discovery Institute, Monash University, Clayton, Vic, 3800,
• Background [10] Ivermectin: a potential candidate for the treatment of COVID 19 Dhyuti Gupta 1, Ajaya Kumar Sahoo 1, Alok Singh ∗,1 Department of Pharmacology, All India Institute of Medical Sciences, Raipur, Chhattisgarh, India
• Background [11] Loukas A, Hotez PJ. Chemotherapy of helminth infections. In: Brunton LL, Lazo JS, Parker KL, editors. Goodman & Gilman's The pharmacological basis of therapeutics. 11th ed. New York (N.Y.): McGraw Hill; 2006. p. 1073-1093.
• Background Guzzo CA, Furtek CI, Porras AG, Chen C, Tipping R, Clineschmidt CM, Sciberras DG, Hsieh JY, Lasseter KC. Safety, tolerability, and pharmacokinetics of escalating high doses of ivermectin in healthy adult subjects. J Clin Pharmacol. 2002 Oct;42(10):1122-33. doi: 10.1177/009127002401382731.
• Background Navarro M, Camprubi D, Requena-Mendez A, Buonfrate D, Giorli G, Kamgno J, Gardon J, Boussinesq M, Munoz J, Krolewiecki A. Safety of high-dose ivermectin: a systematic review and meta-analysis. J Antimicrob Chemother. 2020 Apr 1;75(4):827-834. doi: 10.1093/jac/dkz524.
• Background [14] Dalvi P.S.; Singh A; Trivedi HR; et al. (2011).
• Background McCullough PA, Kelly RJ, Ruocco G, Lerma E, Tumlin J, Wheelan KR, Katz N, Lepor NE, Vijay K, Carter H, Singh B, McCullough SP, Bhambi BK, Palazzuoli A, De Ferrari GM, Milligan GP, Safder T, Tecson KM, Wang DD, McKinnon JE, O'Neill WW, Zervos M, Risch HA. Pathophysiological Basis and Rationale for Early Outpatient Treatment of SARS-CoV-2 (COVID-19) Infection. Am J Med. 2021 Jan;134(1):16-22. doi: 10.1016/j.amjmed.2020.07.003. Epub 2020 Aug 7.
• Background [16] Goodman and Gilman's The Pharmacological Basis of Therapeutics, 11th edition, page 122, 1084-1087.
• Background [17] COMFORTIS® and ivermectin interaction Safety Warning Notification
• Background Smith K, Leyden JJ. Safety of doxycycline and minocycline: a systematic review. Clin Ther. 2005 Sep;27(9):1329-42. doi: 10.1016/j.clinthera.2005.09.005.
• Background [19] Information for Clinicians on Therapeutic Options for COVID-19 Patients. www.cdc.gov/coronavirus/2019-ncov/hcp/therapeutic-options.
• Background Teuwen LA, Geldhof V, Pasut A, Carmeliet P. COVID-19: the vasculature unleashed. Nat Rev Immunol. 2020 Jul;20(7):389-391. doi: 10.1038/s41577-020-0343-0.
• Background Sodhi M, Etminan M. Therapeutic Potential for Tetracyclines in the Treatment of COVID-19. Pharmacotherapy. 2020 May;40(5):487-488. doi: 10.1002/phar.2395. Epub 2020 May 4. No abstract available.
• Background Henehan M, Montuno M, De Benedetto A. Doxycycline as an anti-inflammatory agent: updates in dermatology. J Eur Acad Dermatol Venereol. 2017 Nov;31(11):1800-1808. doi: 10.1111/jdv.14345. Epub 2017 Jun 7.
• Background Yoshikawa T, Hill T, Li K, Peters CJ, Tseng CT. Severe acute respiratory syndrome (SARS) coronavirus-induced lung epithelial cytokines exacerbate SARS pathogenesis by modulating intrinsic functions of monocyte-derived macrophages and dendritic cells. J Virol. 2009 Apr;83(7):3039-48. doi: 10.1128/JVI.01792-08. Epub 2008 Nov 12.
• Background Kritas SK, Ronconi G, Caraffa A, Gallenga CE, Ross R, Conti P. Mast cells contribute to coronavirus-induced inflammation: new anti-inflammatory strategy. J Biol Regul Homeost Agents. 2020 January-February,;34(1):9-14. doi: 10.23812/20-Editorial-Kritas.
• Background Dutta K, Basu A. Use of minocycline in viral infections. Indian J Med Res. 2011 May;133(5):467-70.
• Background Zakeri B, Wright GD. Chemical biology of tetracycline antibiotics. Biochem Cell Biol. 2008 Apr;86(2):124-36. doi: 10.1139/O08-002.
• Background Phillips JM, Gallagher T, Weiss SR. Neurovirulent Murine Coronavirus JHM.SD Uses Cellular Zinc Metalloproteases for Virus Entry and Cell-Cell Fusion. J Virol. 2017 Mar 29;91(8):e01564-16. doi: 10.1128/JVI.01564-16. Print 2017 Apr 15.
• Background Rothan HA, Mohamed Z, Paydar M, Rahman NA, Yusof R. Inhibitory effect of doxycycline against dengue virus replication in vitro. Arch Virol. 2014 Apr;159(4):711-8. doi: 10.1007/s00705-013-1880-7. Epub 2013 Oct 19.
• Background Sargiacomo C, Sotgia F, Lisanti MP. COVID-19 and chronological aging: senolytics and other anti-aging drugs for the treatment or prevention of corona virus infection? Aging (Albany NY). 2020 Mar 30;12(8):6511-6517. doi: 10.18632/aging.103001. Epub 2020 Mar 30.
• Background [30] Beigel JH, Tomashek KM, Dodd LE, Mehta AK, Zingman BS, Kalil AC, et al. (May 2020).

Drugs

Indications