Atovaquone and Azithromycin Combination for Confirmed COVID-19 Infection

Open-Label, Non-Randomized Study to Evaluate Anti-Malarial/Anti-Infective Combination Therapies in Patients With Confirmed COVID-19 Infection

This study will evaluate anti-malarial/anti-infective single-agent and in combination for patients with confirmed COVID-19 infection. The first combination to be evaluated is atovaquone and azithromycin.

Study Overview

• Status: Terminated
• Conditions: Covid19
• Intervention / Treatment: Drug: Atovaquone/Azithromycin

Detailed Description

This is an open-label, non-randomized study to evaluate anti-malarial/anti-infective single-agents and combination therapies for patients with confirmed COVID-19 infection requiring therapy as determined by risk factors for complication (age, comorbid illness) or the presence of respiratory compromise. The first combination to be evaluated is atovaquone/azithromycin. Other combinations may be added to the study at future amendments as information of potential benefit arises. The first part of the study will enroll 25 evaluable male and female patients 18 years of age or older with confirmed COVID-19 infection.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • HonorHealth

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 95 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and Female patients age 18 years or older
• COVID-19 confirmed positive test results
• High risk for complications including with Medium (5-6) or High (More than or equal to 7) NEWS score
• Hematology criteria: ANC >500 cells/mcl, HGB >9 g/dl, Platelet count >75,000/mcl
• Metabolic criteria: Serum creatinine <2.0 mg/dl or calculated creatinine clearance (using Cockcroft-Gault) >30 ml/min, AST/ALT <5x ULN AND Total Bilirubin WNL (for patients with Gilbert's disease, direct bilirubin <ULN)

Exclusion Criteria:

• COVID-19 negative test result
• Inability to adhere to study protocol requirements
• Inability to provide informed consent
• Other acute or chronic medical or psychiatric condition that in the judgment of the investigator would make the participant inappropriate to take part in the study
• Pregnant and breastfeeding individuals
• QTc interval greater than 470 msecs at baseline
• History of hypersensitivity to atovaquone and/or azithromycin.
• History of known intolerance to atovaquone and/or azithromycin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Atovaquone/Azithromycin; Atovaquone 750 mg PO Q12H for up to 10 days Azithromycin 500 mg PO Day 1 followed by 250 mg PO daily for up to 10 days (Days 2-10)	Drug: Atovaquone/Azithromycin; Atovaquone 750 mg PO Q12H for up to 10 Days Azithromycin 500 mg PO Daily 1 followed by 250 mg PO Daily for up to 10 days (days 2-10); Other Names: Mepron/Zithromax

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Virology Cure Rate	COVID-19 serology testing	10 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of GI adverse events	Measure incidence of diarrhea, vomiting, nausea and constipation	47 days
Cardiac Toxicity	12-Lead ECG daily if QTc >500 msec	10 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in WBC w Diff, B cells, T cells, NK cells	Measure blood counts	10 days
Changes in cytokine levels, IL-1, IL-6, IL-12, IL-18, TNF-a	Measure changes in plasma cytokines throughout course of infection	10 days

Collaborators and Investigators

• Sponsor: HonorHealth Research Institute
• Investigators: Principal Investigator: Michael Gordon, MD, HonorHealth Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): April 20, 2020
• Primary Completion (Actual): February 11, 2022
• Study Completion (Actual): February 11, 2022

Study Registration Dates

• First Submitted: April 7, 2020
• First Submitted That Met QC Criteria: April 7, 2020
• First Posted (Actual): April 9, 2020

Study Record Updates

• Last Update Posted (Actual): March 4, 2022
• Last Update Submitted That Met QC Criteria: February 16, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Atovaquone; Azithromycin
• Other Study ID Numbers: HRI-COVID-19-Anti-Malarial-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No