A Study of Combination Therapies to Treat COVID-19 Infection

Study Overview
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Brief Summary
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This study seeks to determine whether dual or quadruple therapy is more effective in treating COVID-19.

Detailed Description
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In this study, patients will be administered either dual or quadruple therapy and have PCR tests run daily to determine efficacy as indicated by time to non-infectivity

Official Title
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A Phase IIa Randomized, Controlled Study of Combination Therapies to Treat COVID-19 Infection

Conditions
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COVID, COVID-19, Corona Virus Infection, Coronavirus Infection, Coronavirus Sars-Associated as Cause of Disease Classified Elsewhere, Coronavirus-19, SARS-CoV 2, SARS Pneumonia

Intervention / Treatment
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* Drug: hydroxychloroquine
* Drug: Azithromycin
* Drug: Ritonavir
* Drug: Lopinavir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent, demonstrating that the subject understands the procedures required for the study and the purpose of the study Healthy, ambulant male or female subjects 18 years of age to 65 years of age Positive test for COVID-19 by RT-PCR at screening Subjects must agree to practice at least one highly effective method of birth control for the duration of the study. This includes condoms with spermicide, oral birth control pills, contraceptive implants, intra-uterine devices, or diaphragms. Subjects not of reproductive potential will be exempt (e.g. post-menopausal, surgically sterilized) Subjects must agree they will do their best to attend the treatment facility daily for 10 days Exclusion Criteria: Refusal to sign informed consent form Negative test for COVID-19 by RT-PCR at screening Severe disease symptomatically including pneumonia, respiratory distress, tachypnea, shortness of breath, temperature > 38 degrees; pleuritic pain, or frequent cough. Known drug allergy to any of the investigational medications Currently taking medication with known drug interactions with investigational medications (listed in appendix) Prescription or other antiviral medications Any comorbidities which constitute health risk for the subject Pregnant or lactating females; weight < 110lb; porphyria established retinal disease Inability to attend daily for 10 days Any contraindications for treatment with hydroxychloroquine Hypoglycemia Known G6PD deficiency Porphyria Anemia Neutropenia Alcoholism Myasthenia gravis Skeletal muscle disorders Maculopathy Changes in visual field Liver disease Psoriasis History of QT >500msec History of torsades de pointes Anemia from pyruvate kinase and G6PD deficiencies Abnormal EKG with QT prolongation acquired or from birth History of jaundice or high fevers prior to developing COVID-19 Treatment with any of the medications listed in Appendix II Treatment with any anti-epileptic medication Treatment with any other drug not listed that affects the QT interval

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dual Therapy<br>Dual Therapy utilizing hydroxychloroquine and azithromycin. | Drug: hydroxychloroquine<br>* Treatment with the drug hydroxychloroquine<br>* Other names: Plaquenil;Drug: Azithromycin<br>* Treatment with the drug azithromycin<br>* Other names: Zithromax;|
| Experimental: Quadruple Therapy<br>Quadruple therapy utilizing hydroxychloroquine, lopinavir, ritonavir, and azithromycin | Drug: hydroxychloroquine<br>* Treatment with the drug hydroxychloroquine<br>* Other names: Plaquenil;Drug: Azithromycin<br>* Treatment with the drug azithromycin<br>* Other names: Zithromax;Drug: Ritonavir<br>* Treatment with the drug ritonavir<br>* Other names: norvir;Drug: Lopinavir<br>* Treatment with the drug lopinavir<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of Treatment by Reduced Symptoms NEWS (National Early Warning System) scores | Time to reduced symptoms in each treatment group as indicated by NEWS scores, which rate patient status based on a zero to three scale for 8 parameters. These values are added up to create the NEWS score. The lower the NEWS score, the better the patient's clinical condition. Zero is the lowest possible score, whereas 7 or greater represents a high degree of clinical risk. | 6 months | 
| Efficacy of Treatment by Time to Non-Infectivity | Time to non-infectivity as measured by PCR testing | 10 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of Dual Therapy as Measured by Symptoms rated on the NEWS (National Early Warning System) sores | Patient symptoms will be recorded using the NEWS system, which rates patient status based on a zero to three scale for 8 parameters. These values are added up to create the NEWS score. The lower the NEWS score, the better the patient's clinical condition. Zero is the lowest possible score, whereas 7 or greater represents a high degree of clinical risk. | 6 months | 
| Safety of Quadruple Therapy as Measured by Symptoms rated on the NEWS (National Early Warning System) scores. | Patient symptoms will be recorded using the NEWS system, which rates patient status based on a zero to three scale for 8 parameters. These values are added up to create the NEWS score. The lower the NEWS score, the better the patient's clinical condition. Zero is the lowest possible score, whereas 7 or greater represents a high degree of clinical risk. | 6 months | 
| Safety of Dual Therapy as Measured by Complete Blood Count | Changes in blood parameters measured in a Complete Blood Count (CBC). | 6 months | 
| Safety of Quadruple Therapy as Measured by Complete Blood Count | Changes in blood parameters measured in a Complete Metabolic Panel. | 6 months | 
| Safety of Dual Therapy as Measured by Metabolic Panel -Albumin | Changes in serum albumin levels | 6 months | 
| Safety of Quadruple Therapy as Measured by Metabolic Panel - Albumin | Changes in serum albumin levels | 6 months | 
| Safety of Quadruple Therapy as Measured by Metabolic Panel - A/G Ratio | Changes in serum albumin/globulin ratio | 6 months | 
| Safety of Dual Therapy as Measured by Metabolic Panel A/G Ratio | Changes in serum albumin/globulin ratio | 6 months | 
| Safety of Quadruple Therapy as Measured by Metabolic Panel - Alkaline Phosphatase | Changes in serum alkaline phosphatase levels | 6 months | 
| Safety of Dual Therapy as Measured by Metabolic Panel Alkaline Phosphatase | Changes in serum alkaline phosphatase levels | 6 months | 
| Safety of Dual Therapy as Measured by Metabolic Panel - AST | Changes in serum AST levels | 6 months | 
| Safety of Quadruple Therapy as Measured by Metabolic Panel - AST | Changes in serum AST levels | 6 months | 
| Safety of Quadruple Therapy as Measured by Metabolic Panel - ALT | Changes in serum ALT levels | 6 months | 
| Safety of Dual Therapy as Measured by Metabolic Panel ALT | Changes in serum ALT levels | 6 months | 
| Safety of Dual Therapy as Measured by Metabolic Panel BUN/Creatinine Ratio | Changes in serum BUN/Creatinine Ratio | 6 months | 
| Safety of Quadruple Therapy as Measured by Metabolic Panel BUN/Creatinine Ratio | Changes in serum BUN/Creatinine Ratio | 6 months | 
| Safety of Quadruple Therapy as Measured by Metabolic Panel - BUN | Changes in serum Blood Urea Nitrogen levels | 6 months | 
| Safety of Dual Therapy as Measured by Metabolic Panel - BUN | Changes in serum Blood Urea Nitrogen levels | 6 months | 
| Safety of Dual Therapy as Measured by Metabolic Panel - Calcium | Changes in serum calcium levels | 6 months | 
| Safety of Quadruple Therapy as Measured by Metabolic Panel - Calcium | Changes in serum calcium levels | 6 months | 
| Safety of Quadruple Therapy as Measured by Metabolic Panel - Carbon Dioxide | Changes in serum carbon dioxide levels | 6 months | 
| Safety of Dual Therapy as Measured by Metabolic Panel - Carbon Dioxide | Changes in serum carbon dioxide levels | 6 months | 
| Safety of Dual Therapy as Measured by Metabolic Panel - Chloride | Changes in serum chloride levels | 6 months | 
| Safety of Quadruple Therapy as Measured by Metabolic Panel - Chloride | Changes in serum chloride levels | 6 months | 
| Safety of Quadruple Therapy as Measured by Metabolic Panel - Creatinine | Changes in serum creatinine levels | 6 months | 
| Safety of Dual Therapy as Measured by Metabolic Panel - Creatinine | Changes in serum creatinine levels | 6 months | 
| Safety of Dual Therapy as Measured by Metabolic Panel - Globulin | Changes in serum globulin levels | 6 months | 
| Safety of Quadruple Therapy as Measured by Metabolic Panel - Globulin | Changes in serum globulin levels | 6 months | 
| Safety of Quadruple Therapy as Measured by Metabolic Panel - Glucose | Changes in blood glucose levels | 6 months | 
| Safety of Dual Therapy as Measured by Metabolic Panel - Glucose | Changes in blood glucose levels | 6 months | 
| Safety of Dual Therapy as Measured by Metabolic Panel - Potassium | Changes in blood potassium levels | 6 months | 
| Safety of Quadruple Therapy as Measured by Metabolic Panel - Potassium | Changes in blood potassium levels | 6 months | 
| Safety of Quadruple Therapy as Measured by Metabolic Panel - Total Bilirubin | Changes in serum total bilirubin levels | 6 months | 
| Safety of Dual Therapy as Measured by Metabolic Panel - Total Bilirubin | Changes in serum total bilirubin levels | 6 months | 
| Safety of Dual Therapy as Measured by Metabolic Panel - Total Protein | Changes in serum total protein levels | 6 months | 
| Safety of Quadruple Therapy as Measured by Metabolic Panel - Total Protein | Changes in serum total protein levels | 6 months | 
| Safety of Dual Therapy as Measured by Treatment Related SAE | Presence or absence of treatment related serious adverse events Grade III or higher | 6 months | 
| Safety of Quadruple Therapy as Measured by Treatment Related SAE | Presence or absence of treatment related serious adverse events Grade III or higher | 6 months |