Novel Agents for Treatment of High-risk COVID-19 Positive Patients
Novel Agents for Treatment of High-risk COVID-19 Positive Patients
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.
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