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

NCT ID: NCT04374019

Last Updated: 2022-01-20

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-05-01
• Study Completion Date: 2022-01-12

Brief Summary

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.

Detailed Description

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.

Conditions

COVID; Sars-CoV2

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm C: Ivermectin

Ivermectin

Group Type: EXPERIMENTAL

Ivermectin

Intervention Type: DRUG

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)

Arm D: Camostat Mesilate

Camostat Mesilate

Group Type: EXPERIMENTAL

Camostat Mesilate

Intervention Type: DRUG

Days 1-14: 2 tab TID after a meal (600 mg total daily dose)

Arm E: Artemesia annua

Artemesia annua tea or coffee

Group Type: EXPERIMENTAL

Artemesia annua

Intervention Type: DIETARY_SUPPLEMENT

Days 1-14: tea or coffee pod TID (1350 mg total daily dose)

Arm F: Artesunate

Artesunate

Group Type: EXPERIMENTAL

Artesunate

Intervention Type: DRUG

Days 1-14:

Interventions

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)

Intervention Type: DRUG

Camostat Mesilate

Days 1-14: 2 tab TID after a meal (600 mg total daily dose)

Intervention Type: DRUG

Artemesia annua

Days 1-14: tea or coffee pod TID (1350 mg total daily dose)

Intervention Type: DIETARY_SUPPLEMENT

Artesunate

Days 1-14:

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Susanne Arnold

OTHER

Sponsor Role: lead

Responsible Party

Susanne Arnold

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Susanne Arnold, MD

Role: PRINCIPAL_INVESTIGATOR

University of Kentucky

Locations

University of Kentucky Markey Cancer Center

Lexington, Kentucky, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

MCC-20-COVID-01-PMC

Identifier Type: -

Identifier Source: org_study_id