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

NCT04729140 | Unknown Phase 4 DMC FDA Drug

• 1 other identifier: COVIVER-OUT PLUS
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Covid19

Keywords

COVID 19; Ivermectin; Doxycycline

Outcome Measures

Primary Outcomes (1)

• Decreased admission rate to the hospital secondary to respiratory illness related to COVID-19

  The investigators will be assessing for decreased admission rate to the hospital secondary to respiratory illness related to COVID-19. This will be assessed over the duration of 5 weeks.

  5 weeks

Secondary Outcomes (62)

• Decrease in total duration of symptoms secondary to respiratory illness related to COVID-19

  5 weeks

• Assessment of White Blood Cell Count

  2 weeks

• Assessment of Hemoglobin level

  2 weeks

• Assessment of Hematocrit level

  2 weeks

• Assessment of Platelet Count

  2 weeks

Study Arms (3)

Ivermectin plus Doxycycline

ACTIVE COMPARATOR

Ivermectin 200 mcg/kg on day 1 and day 2-plus doxycycline 100 mg tablets twice a day for seven days Body Weight (kg) Single oral Dose number of 3 mg tablets of Ivermectin 15-24 kg 1 tablet 25-35 kg 2 tablets 36-50 kg 3 tablets 51-65 kg 4 tablets 66-79 kg 5 tablets 80-109 kg 6 tablets \>110 kg 7 tablets

Drug: Ivermectin Tablets; Drug: Doxycycline Tablets

Ivermectin plus Placebo

ACTIVE COMPARATOR

Ivermectin 200 mcg/kg on day 1 and day 2-plus placebo tablet twice a day for seven days Body Weight (kg) Single oral Dose number of 3 mg tablets of Ivermectin and Placebo 15-24 kg 1 tablet 25-35 kg 2 tablets 36-50 kg 3 tablets 51-65 kg 4 tablets 66-79 kg 5 tablets 80-109 kg 6 tablets \>110 kg 7 tablets

Drug: Ivermectin Tablets; Drug: Placebo

Placebo plus Placebo

PLACEBO COMPARATOR

Placebo (number of tablets according to weight) plus placebo twice a day for seven days Body Weight (kg) Single oral Dose number of 3 mg tablets of Placebo 15-24 kg 1 tablet 25-35 kg 2 tablets 36-50 kg 3 tablets 51-65 kg 4 tablets 66-79 kg 5 tablets 80-109 kg 6 tablets \>110 kg 7 tablets

Drug: Placebo

Interventions

Ivermectin Tablets DRUG

Double-blinded, prospective, placebo controlled outpatient randomized clinical trial.

Ivermectin plus Doxycycline; Ivermectin plus Placebo

Doxycycline Tablets DRUG

Double-blinded, prospective, placebo controlled outpatient randomized clinical trial.

Ivermectin plus Doxycycline

Placebo DRUG

Double-blinded, prospective, placebo controlled outpatient randomized clinical trial.

Ivermectin plus Placebo; Placebo plus Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age greater than or equal to 18
• Willing and able to provide verbal /telephonic/Personal or computer based Informed Consent
• Experiencing symptoms of COVID-19 illness and tested positive for SARS CoV-2 with either PCR, NAAT or antigen testing
• Residents in a Nursing Home or long-term care facility
• Immunocompromised state, including solid organ transplant, HIV infection, other immune deficiency, immunosuppressant medication including systemic corticosteroids
• Chronic lung disease, including Chronic Obstructive Pulmonary Disease (COPD), moderate to severe asthma, cystic fibrosis, pulmonary fibrosis
• Cardiovascular Disease
• Cancer
• Hypertension
• Obesity (body mass index \[BMI greater then or equal to 30 kg/m\^2\]
• Diabetes Mellitus
• Chronic Kidney Disease
• Chronic Liver Disease
• Cerebrovascular Disease
• Neurological Disorders including dementia

You may not qualify if:

• Participants under the age of 18
• Received any COVID vaccine within the last 30 days
• Contraindications to Ivermectin or Doxycycline
• History of Seizure Disorder or Epilepsy
• History of Myocardial Infarction or Heart Attack within the last one month
• Already receiving Ivermectin or Doxycycline for treatment of any other disease or disorder
• Allergies to Ivermectin or Doxycycline including angioedema, severe asthma, exfoliative dermatitis, Steven Jonson syndrome or psoriasis
• History of angioedema, exfoliative dermatitis, Steven Johnson syndrome, psoriasis
• Currently Pregnant or planning to conceive soon
• Breastfeeding
• History of prior Clostridium Difficile infection

Sponsors & Collaborators

• Max Health, Subsero Health: lead

Study Sites (1)

MAX HEALTH, Subsero Health 2055 Wood Street, Suite 100

Sarasota, Florida, 34237, United States

RECRUITING

Related Publications (30)

• [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.

  PMID: 32004427 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.

  PMID: 32109011 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 covid19@pscflorida.com

  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.

  PMID: 12362927 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.

  PMID: 31960060 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.

  PMID: 32771461 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.

  PMID: 16291409 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.

  PMID: 32439870 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.

  PMID: 32267566 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.

  PMID: 28516469 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.

  PMID: 19004938 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.

  PMID: 32013309 BACKGROUND

• Dutta K, Basu A. Use of minocycline in viral infections. Indian J Med Res. 2011 May;133(5):467-70.

  PMID: 21623029 BACKGROUND

• Zakeri B, Wright GD. Chemical biology of tetracycline antibiotics. Biochem Cell Biol. 2008 Apr;86(2):124-36. doi: 10.1139/O08-002.

  PMID: 18443626 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.

  PMID: 28148786 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.

  PMID: 24142271 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.

  PMID: 32229706 BACKGROUND

• [30] Beigel JH, Tomashek KM, Dodd LE, Mehta AK, Zingman BS, Kalil AC, et al. (May 2020).

  BACKGROUND

MeSH Terms

Conditions

COVID-19

Interventions

Ivermectin; Doxycycline

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Polyketides; Lactones; Organic Chemicals; Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Study Officials

• Werther Marciales, MD

  Clinical Trial Principal Investigator

  PRINCIPAL INVESTIGATOR

• Ryan Salom

  sub Clinical Trial Prinicipal Investigator

  PRINCIPAL INVESTIGATOR

• Faheem Ahmad, MD

  sub Clinical Trial Prinicipal Investigator

  PRINCIPAL INVESTIGATOR

• Divisha Sharma, MD

  Clinical Trial Investigator

  PRINCIPAL INVESTIGATOR

• Nicholas Guy Ross, DO

  Clinical Trial Investigator

  PRINCIPAL INVESTIGATOR

• Terry Fredeking

  Clinical Trial Investogator

  PRINCIPAL INVESTIGATOR

• Michael Ricciardi, PhD

  Clinical Trial Investogator

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Inita Bedi

CONTACT

941 371 3500; ibedi@mymaxdoc.com

Werther Marciales, MD

CONTACT

941 545 8857; werther40@msn.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Data analysis will be carried out using statistical package for the social sciences software (SPSS). Interim data analysis will be performed at three different levels of the number of participants starting at sample size 20, 30 and 50. If no significant findings are obtained from the data at N=50, then it will add more participants to the study to achieve statistical significance. Sponsor and Principal Investigator will defer data analysis to a statistician. A Data Monitoring Committee (DMC) is going to be established in order to review accumulating trial data by treatment group in order to monitor patient safety and efficacy, ensure validity and integrity of the trial and make benefit-risk assessment. This is going to be conducted by a third party external DMC.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Double-blinded, prospective, placebo controlled outpatient randomized clinical trial.

Study Record Dates

• First Submitted: December 30, 2020
• First Posted: January 28, 2021
• Study Start: December 28, 2020
• Primary Completion: December 28, 2021
• Study Completion: March 28, 2022
• Last Updated: April 1, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: December 28 2020 to March 28 2022

Locations

US (1)