This is a multi-arm, phase II trial for rapid efficacy and toxicity assessment of multiple therapies immediately after COVID19 positive testing in high-risk individuals. Therapies include stand-alone or combination treatment with hydroxychloroquine, azithromycin, ivermectin, or camostat mesilate, artemesia annua. The hypothesis of this study is that the addition of agents that inhibit viral entry or replication of SARS-CoV-2 virus replication in will be devoid of additional moderate to severe toxicities, will prevent clinical deterioration, and will improve viral clearance in high risk individuals.
Coronavirus Disease 2019 (COVID-19) is a highly contagious disease, caused by a novel
enveloped RNA beta-coronavirus, also known as severe acute respiratory syndrome coronavirus-2
(SARS-CoV-2). The first case of this unprecedented outbreak "pneumonia of unknown etiology"
was reported in Wuhan City, Hubei Province, China on December 8th, 2019 and reported to the
World Health Organization (WHO) on December 31st, 2019. WHO declared a COVID-19 global
emergency on January 30, 2020, and then categorized the outbreak as a pandemic on March 11,
2020. As of April 22, 2020, more than 2,628,894 confirmed cases of COVID-19 worldwide and
182,740 people globally have died from COVID-19 since it emerged in China, according to the
data from Johns Hopkins University.
While the majority of patients with COVID-19 develop mild or uncomplicated illness,
approximately 20-30% of hospitalized patients have required intensive care support and 5% of
those have multi-organ failure or shock. The case fatality rate ranges from 1 to 4% and it is
higher among those with pre-existing comorbid conditions such as cardiovascular disease,
diabetes mellitus, obesity, chronic respiratory disease, hypertension and cancer. The vast
majority of patients present with fever (83-99%), cough (59-82%), fatigue (44-70%), anorexia
(40-84%), shortness of breath (31-40%), sputum production (28-33%), myalgias (11-35%). Less
than 10% of patients will present with headache, confusion, rhinorrhea, sore throat,
hemoptysis, vomiting, or diarrhea. Anosmia or ageusia proceeding the onset of respiratory
symptoms has been anecdotally reported.
To date, treatments for COVID-19 in high risks individuals remain experimental and
therapeutic strategies to deal with the infection are at best supportive, with prevention
aimed at reducing transmission in the community as the best weapon. No proven therapies have
been demonstrated to prevent the progression of COVID-19 to severe illness and this is a
critical unmet need for high-risk individuals and warrants study. Recently, the Infectious
Disease Society of America has made recommendations for the treatment of patients with
COVID-19, focusing on inpatient care, and recommending randomized trials where possible as
the best step to improve treatment outcomes and to increase our understanding of this
coronavirus pandemic. Discoveries in this area may inform clinicians on effective treatment
for low-risk individuals who progress to severe illness, as well.
Drug: Ivermectin
Ivermectin:
Days 1-2: Weight < 75kg: 4 tabs (12 mg total daily dose) Days 1-2: Weight > 75kg: 5 tabs (15 mg total daily dose)
Drug: Camostat Mesilate
Days 1-14: 2 tab TID after a meal (600 mg total daily dose)
Dietary Supplement: Artemesia annua
Days 1-14: tea or coffee pod TID (1350 mg total daily dose)
Drug: Artesunate
Days 1-14:
Inclusion Criteria
- Age ≥18 years
- Laboratory-confirmed SARS-CoV-2 infection within the past 7 days or the presence of
symptoms or physical examination signs providing high probability of COVID-19 disease
- Patients must have adequate organ and marrow function measured within the last 6
months
- Subjects must have at least one of the following high-risk features for clinical
deterioration:
- Hypertension
- Diabetes Mellitus
- Moderate to severe Chronic Obstructive Pulmonary Disease, Emphysema, Cystic
Fibrosis, or Asthma
- Cancer patients who have received any immunosuppressive drugs within a year from
enrollment
- Sickle Cell disease or thalessemia
- Age > or = 50
- BMI > or = 30
- Living in a nursing home or long-term facility
- Underlying serious heart condition as determined by the treating physician
- Immunocompromised subject as defined by the treating physician or COVID-19
Telehealth Treatment Team
Exclusion Criteria
- Severe or life threating COVID
- Weight less than 45 kg.
- Pregnant or breast-feeding females
- Subjects on dialysis or with creatinine clearance < 45 ml/min
- Existing DMID Toxicity Scale for Determining Severity of Adverse Events grade 3 or
greater hepatic failure
- Previously documented moderate or severe retinopathy or macular degeneration
- Uncontrolled Seizure disorder
- Prolonged QT, defined as QTc ≥470 milliseconds for men and as QTc ≥480 for women using
Bazett's formula
- Known allergy to artesunate, artemisia annua, hydroxychloroquine, macrolides,
4-aminoquinolines, camostat mesilate, or other agents to be used in the trial.
- Currently receiving any study medications for other indications
- Concurrent use of medication that would cause drug-drug interactions
- Patients with psychiatric illness/social situations that would limit compliance
University of Kentucky Markey Cancer Center
Lexington, Kentucky, United States
Susanne Arnold, MD, Principal Investigator
University of Kentucky