The (HD)IVACOV Trial (The High-Dose IVermectin Against COVID-19 Trial)

NCT04712279 | Unknown Phase 2 DMC

• 1 other identifier: CORPO-DRUG-SARSCoV2-001
• Study Type: interventional
• Target: 294
• Locations: 0 countries
• Sites: N/A

Brief Summary

Ivermectin, a classical antiparasitic and anti-scabies agent, has demonstrated antiviral activity for a variety of viruses including chikungunya virus, zyka virus and dengue virus and was tested as a potentially effective for COVID-19. Although ivermectin demonstrated potent in vitro action by reducing viral load by 5000x after 48 hours of incubation, simultaneous pharmacokinetics simulations suggested that the minimum effective concentrations would be unfeasible to be reached within safety range (EC-50 = 2 Micromol). However, despite the theoretical unfeasible concentrations to be achieved, preliminary observational yet well-structured studies followed by randomized clinical trials (RCTs) demonstrated ivermectin efficacy when combined with hydroxychloroquine, doxycycline or azithromycin, which was corroborated by a recent systematic review and metanalysis. In common, a dose-response effect for effectiveness was observed, and no adverse effects was reported at any dose between 0.2mg/kg/day and 1.0mg/kg/day. Based on the scientific rationale combined with the preliminary evidence, ivermectin has sufficient evidence to be tested in higher doses in a RCT for COVID-19. The investigators propose to test ivermectin at high doses as a treatment for patients recently diagnosed with COVID-19, aiming to explore the possible protective role of high-dose ivermectin in SARS-CoV-2 infection in terms of reduction of clinic and virologic disease duration, and prevention of oxygen use, hospitalization, mechanical ventilation, death, and post-COVID persisting symptoms.

Conditions

Covid19

Keywords

COVID-19; SARS-CoV-2; Covid19; Ivermectin

Outcome Measures

Primary Outcomes (1)

• World Health Organization (WHO) Clinical Progression Scale [0 to 10; 0 = uninfected; 10 = death]

  Treatment efficacy of high-dose Ivermectin relative to placebo arm as assessed by World Health Organization (WHO) Clinical Progression Scale \[0 to 10; 0 = uninfected; 10 = death\]

  Day 14

Secondary Outcomes (38)

• World Health Organization (WHO) COVID=19 Ordinal Scale for Clinical Improvement [1 to 8; 1 = not hospitalized, no limitation on activities; 8 = death] [Time Frame: Day 7]

  Day 7

• Time-to-recovery

  Day 28

• Viral load

  Day 5

• Positivity rate of rtPCR-SARS-CoV-2 (qualitative analysis)

  Day 5

• Duration of fatigue

  Day 14

Study Arms (3)

Ivermectin 0.6mg/kg/day

ACTIVE COMPARATOR

Drug: Ivermectin 0.6mg/kg/day; Drug: Hydroxychloroquine

Ivermectin 1.0mg/kg/day

ACTIVE COMPARATOR

Drug: Ivermectin 1.0mg/kg/day; Drug: Hydroxychloroquine

Placebo

PLACEBO COMPARATOR

Drug: Placebo; Drug: Hydroxychloroquine

Interventions

Ivermectin 0.6mg/kg/day DRUG

Use of ivermectin 0.6m/kg/day q.d.for 05 days

Ivermectin 0.6mg/kg/day

Ivermectin 1.0mg/kg/day DRUG

Ivermectin 1.0mg/kg/day q.d. for 05 days

Ivermectin 1.0mg/kg/day

Placebo DRUG

Placebo q.d.for 05 days

Placebo

Hydroxychloroquine DRUG

Hydroxychloroquine 200mg/day q.d. for 05 days

Ivermectin 0.6mg/kg/day; Ivermectin 1.0mg/kg/day; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Laboratory or clinically confirmed positive SARS-CoV-2 rtPCR test (AndroCoV Clinical Scoring for COVID-19 Diagnosis1) within 7 days prior to randomization
• ≥18 years old
• Laboratory confirmed positive SARS-CoV-2 rtPCR test within 7 days prior to randomization
• Clinical status on the COVID-19 Ordinal Scale (defined in Section 5.1) of 1 to 3
• Subject (or legally authorized representative) gives written informed consent prior to performing any study procedures
• Subject (or legally authorized representative) agree that subject will not participate in another COVID-19 trial while participating in this study

You may not qualify if:

• Subject enrolled in a study to investigate a treatment for COVID-19
• Require oxygen use, hospitalization or mechanical ventilation
• Tachycardia (HR \> 150 bpm) or hypotension (BP \< 90/60 mmHg)
• Patients who are allergic to the investigational product or similar drugs (or any excipients);
• Subjects with QTcF \> 450 ms
• Subjects with uncontrolled medical conditions that could compromise participation in the study - uncontrolled hypertension (BP \> 220/120 mmHg), uncontrolled hypothyroidism (TSH \> 10 iU/L), uncontrolled diabetes mellitus (HbA1c \> 12%)
• Alanine Transaminase (ALT) or Aspartate Transaminase (AST) \> 5 times the upper limit of normal.
• Estimated glomerular filtration rate (eGFR) \< 30 ml/min or requiring dialysis
• Subject (or legally authorized representative) not willing or unable to provide informed consent

Sponsors & Collaborators

• Corpometria Institute: lead

Related Publications (11)

• Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, Liu L, Shan H, Lei CL, Hui DSC, Du B, Li LJ, Zeng G, Yuen KY, Chen RC, Tang CL, Wang T, Chen PY, Xiang J, Li SY, Wang JL, Liang ZJ, Peng YX, Wei L, Liu Y, Hu YH, Peng P, Wang JM, Liu JY, Chen Z, Li G, Zheng ZJ, Qiu SQ, Luo J, Ye CJ, Zhu SY, Zhong NS; China Medical Treatment Expert Group for Covid-19. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020 Apr 30;382(18):1708-1720. doi: 10.1056/NEJMoa2002032. Epub 2020 Feb 28.

  PMID: 32109013 RESULT

• Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-1062. doi: 10.1016/S0140-6736(20)30566-3. Epub 2020 Mar 11.

  PMID: 32171076 RESULT

• Lauer SA, Grantz KH, Bi Q, Jones FK, Zheng Q, Meredith HR, Azman AS, Reich NG, Lessler J. The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application. Ann Intern Med. 2020 May 5;172(9):577-582. doi: 10.7326/M20-0504. Epub 2020 Mar 10.

  PMID: 32150748 RESULT

• Li L, Liu J, Qin K. Comparison of double-dose vs standard-dose oseltamivir in the treatment of influenza: A systematic review and meta-analysis. J Clin Pharm Ther. 2020 Oct;45(5):918-926. doi: 10.1111/jcpt.13203. Epub 2020 Jun 4.

  PMID: 32497319 RESULT

• Varghese FS, Kaukinen P, Glasker S, Bespalov M, Hanski L, Wennerberg K, Kummerer BM, Ahola T. Discovery of berberine, abamectin and ivermectin as antivirals against chikungunya and other alphaviruses. Antiviral Res. 2016 Feb;126:117-24. doi: 10.1016/j.antiviral.2015.12.012. Epub 2016 Jan 2.

  PMID: 26752081 RESULT

• Padhy BM, Mohanty RR, Das S, Meher BR. Therapeutic potential of ivermectin as add on treatment in COVID 19: A systematic review and meta-analysis. J Pharm Pharm Sci. 2020;23:462-469. doi: 10.18433/jpps31457.

  PMID: 33227231 RESULT

• Rajter JC, Sherman MS, Fatteh N, Vogel F, Sacks J, Rajter JJ. Use of Ivermectin Is Associated With Lower Mortality in Hospitalized Patients With Coronavirus Disease 2019: The Ivermectin in COVID Nineteen Study. Chest. 2021 Jan;159(1):85-92. doi: 10.1016/j.chest.2020.10.009. Epub 2020 Oct 13.

  PMID: 33065103 RESULT

• Elgazzar, A et al. Efficacy and Safety of Ivermectin for Treatment and prophylaxis of COVID-19 Pandemic. Research Square doi.org/10.21203, 2020

  RESULT

• Chowdhury, ATMM et al. A Randomized Trial of Ivermectin-Doxycycline and Hydroxychloroquine-Azithromycin therapy on COVID19 patients. Research Square: https://doi.org/10.21203/rs.3.rs-38896/v1, 2020.

  RESULT

• Niaee, MS et al. Ivermectin as an adjunct treatment for hospitalized adult COVID-19 patients: A randomized multi-center clinical trial. Research Square: https://doi.org/10.21203/rs.3.rs-109670/v1, 2020.

  RESULT

• Francés-Monerris, A et al. Has Ivermectin Virus-Directed Effects against SARS-CoV-2? Rationalizing the Action of a Potential Multitarget Antiviral Agent. ChemRxiv, 2020.

  RESULT

MeSH Terms

Conditions

COVID-19

Interventions

Ivermectin; Hydroxychloroquine

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; Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Ricardo A Zimerman, MD

  Corpometria Institute

  STUDY DIRECTOR

• Flavio A Cadegiani, MD, PhD

  Corpometria Institute; Applied Biology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Flavio A Cadegiani, MD, PhD

CONTACT

+55 61 99650.6111; flavio.cadegiani@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 13, 2021
• First Posted: January 15, 2021
• Study Start: January 25, 2021
• Primary Completion: March 21, 2021
• Study Completion: April 20, 2021
• Last Updated: January 15, 2021

Record last verified: 2021-01