This phase II trial studies the effect of ivermectin, camostat mesilate, artemisia annua, or artesunate in treating patients with coronavirus disease 2019 (COVID-19) infection who have higher risk of worsening infection. Ivermectin is an antiparasitic drug with potential anti-viral activities and may prevent replication of the virus responsible for the COVID-19. Camostat mesylate is an anti-inflammatory drug with potential antiviral activities. It may prevent viral infection by blocking an enzyme in the cells that is required for the virus entry to infect the cells. Artemisia annua is a botanical plant that may prevent viral growth. Artesunate is a drug extracted from artemisia annua plant that with anti-malaria activity that may also prevent viral growth. Giving ivermectin, camostat mesilate, Artemisia annua, or artesunate may help decrease COVID-19 virus in the body and ultimately help decrease the chance of clinical symptoms getting worse from COVID-19 and may prevent patients’ hospitalization.
Additional locations may be listed on ClinicalTrials.gov for NCT04374019.
See trial information on ClinicalTrials.gov for a list of participating sites.
PRIMARY OBJECTIVE:
I. To rapidly evaluate initial efficacy of multiple potential inhibitors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral replication in COVID-19 positive patients with high-risk factors in order to decrease clinical deterioration, as defined as a less than a 2-point decrease from initial COVID 7-POINT ORDINAL OUTCOMES SCALE within 14 days from study entry.
SECONDARY OBJECTIVES:
I. To assess the decrease in viral load at day 14.
II. To assess the development of severe respiratory or other organ failure in the study population.
III. To assess progression to intensive care unit (ICU) care or ventilation in non-critically ill hospitalized patients and overall study population.
IV. To assess clearance of viral ribonucleic acid (RNA) by polymerase chain reaction (PCR) testing at days 1, 14, 28, and 40 days.
V. To assess mortality, clinical status of subject at day 14, using the COVID 7-point ordinal outcomes scale, and rate of severe adverse events defined as grade 3 non hematologic or greater by Division of Microbiology and Infectious Diseases (DMID) Toxicity Scale for Determining Severity of Adverse Events.
VI. To assess the safety, tolerability and compliance with each regimen.
EXPLORATORY OBJECTIVES:
I. To observe and record the impact of each drug combination on inflammatory markers (procalcitonin, D-dimer, high sensitivity C-reactive protein [hs-CRP]) and their potential prognostic/predictive value.
II. To determine the rate and timeframe of SARS-CoV-2 seroconversion as a marker of acquired immunity via the presence of COVID-19 antibodies in RNA negative patients as a marker of acquired immunity using either a rapid diagnostic test (RDT) or enzyme-linked immunosorbent assay (ELISA) assay.
III. To determine if early detection of elevated inflammatory cytokines are predictive of severe infection or severe disease.
IV. To perform post-hoc covariate adjusted analysis for potential pre-treatment, outcome-prognostic covariates such as age, sex, degree of illness, clinical chemistries, and timing of onset of symptoms relative to study inclusion.
V. To evaluate the effect of COVID-19 on platelet function to assess severe coagulation complications.
VI. To evaluate viral clearance at day 14, 28 and 40.
OUTLINE: Patients are randomized to 1 of 4 arms.
ARM C: Patients receive ivermectin orally (PO) daily on days 1 and 2 in the absence of disease progression or unacceptable toxicity.
ARM D: Patients receive camostat mesilate PO three times daily (TID) on days 1-14 in the absence of disease progression or unacceptable toxicity.
ARM E: Patients receive artemesia annua tea or coffee PO TID on days 1-14 in the absence of disease progression or unacceptable toxicity.
ARM F: Patients receive artesunate PO once daily (QD) on days 1-14 in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 28 and 40 days.
Lead OrganizationUniversity of Kentucky/Markey Cancer Center
Principal InvestigatorSusanne Markesbery Arnold
