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.
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)
Days 1-14: 2 tab TID after a meal (600 mg total daily dose)
Days 1-14: tea or coffee pod TID (1350 mg total daily dose)
University of Kentucky Markey Cancer Center
Lexington, Kentucky, United States
Clinical Deterioration
Number of patients experiencing clinical deterioration. Clinical deterioration is defined as a less than a 2-point change from the initial COVID 7-Point Ordinal Outcomes Scale within 14 days from the study start. This scale ranges from 1-7. Lower scores indicate worse outcomes (death); higher scores indicate fewer symptoms and better outcomes.
Time frame: 14 days
Change in Viral Load
The change in (clearance of) viral RNA will be measured by PCR testing at days 1, 14, 28, and 40 days.
Time frame: 40 days
Rate of Organ Failure
Number of patients that experienced severe respiratory or other organ failure.
Time frame: 28 days
Progression to ICU Care or Ventilation
Percentage of patients requiring ICU admission or ventilation.
Time frame: 28 days
Number of Participants Who Had a Change in Clinical Status Measured by Decrease in COVID 7-point Ordinal Scale
Number of participants who died or had greater than a 2-point decrease in COVID 7-Point Ordinal Outcomes Scale from Day to Day 14. COVID 7-point ordinal outcomes scale: 1. Death 2. Hospitalized on invasive mechanical ventilation or ECMO 3. Hospitalized on non-invasive ventilation or high flow nasal cannula 4. Hospitalized on supplemental oxygen 5. Hospitalized not on supplemental oxygen 6. Not hospitalized with limitation in activity (continued symptoms) 7. Not hospitalized without limitation in activity (no symptoms)
Time frame: 14 days
Mortality
Percentage of patients who have died by day 14.
Time frame: 14 days
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Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
13
Days 1-14:
Rate of Severe Adverse Events
Percentage of patients experiencing severe adverse events, defined as grade 3 non-hematologic or greater by DMID Toxicity Scale for Determining Severity of Adverse Events.
Time frame: 14 days
Number of Patients That Required Oxygen Supplementation
Number of patients that required oxygen supplementation during study treatment Days 1-28
Time frame: 28 days
Number of Patients That Required Mechanical Ventilation
Number of patients that required mechanical ventilation during the study period. Days 1-28
Time frame: 28 days
Number of Patients Who Required Vasopressors
Number of patients who required vasopressor treatment Days 1 to 28
Time frame: 28 days
Number of Patients Who Required ICU Services
Number of patients who required ICU services during study treatment Days 1-28.
Time frame: 28 days
Number of Patients That Required Hospitalization
Number of patients that required hospitalization during study treatment
Time frame: 28 days
Heart Function
Proportion of patients with significant changes in ECG findings, including heart rate, ECG intervals (PR, QTcB, QTcF), conduction changes, or abnormalities including severe QTc prolongation of \> 500 ms.
Time frame: 28 days