Trial of Combination Therapy to Treat COVID-19 Infection

Study Overview
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Brief Summary
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In this trial patients will be treated with either a combination of therapies to treat COVID-19 or a placebo. Treatment will last 10 days, and patients will be followed for 6 months.

Detailed Description
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Patients in this trial will undergo treatment for 10 days with either a combination of therapies or placebo. They will then be followed for an additional 20 days.

Official Title
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A Phase I Double-Blind Randomized Placebo-Controlled Trial of Combination Therapy to Treat COVID-19 Infection

Conditions
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COVID, Covid-19, Corona Virus Infection, Coronavirus Infection, Coronavirus-19, SARS-CoV2, SARS-CoV Infection

Intervention / Treatment
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* Drug: Ivermectin
* Drug: Doxycycline Hcl
* Dietary Supplement: Zinc
* Dietary Supplement: Vitamin D3
* Dietary Supplement: Vitamin C


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 male or female subjects at least 18 years of age Diabetic and obese (BMI > 30) patients will be included in the Trial but randomization will be stratified. Positive test for COVID-19 by RT-PCR or rapid antigen test at screening Subjects must agree to practice at least two highly effective methods of birth control for the duration of the study. One of these must be a barrier method. Exceptions for females and partners of females that are not of childbearing potential. (e.g. surgically sterilized, post-menopausal) Subjects must agree they will attend the treatment facility daily for 10d in the event of failure to attend, the patient will be visited at their home to collect the nasal swab and review data. 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 > 104.0 degrees F, pleuritic pain, or frequent cough. Known drug allergy to any of the investigational medications Currently taking medication with known drug interactions with investigational medications, found in Appendix II Prescription or other antiviral medications Any comorbidities which constitute health risk for the subject including known cardiac arrhythmias - but will be limited to those on hydroxychloroquine Inability to attend daily for 10 days

Ages Eligible for Study
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Minimum Age: 18 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: Active Arm<br>Patients will be treated with a combination of Ivermectin, Doxycycline, Zinc, Vitamin D3 and Vitamin C | Drug: Ivermectin<br>* Treatment days 1, 4, and 8<br>* Other names: Soolantra, Stromectol, Sklice;Drug: Doxycycline Hcl<br>* 10 day treatment<br>* Other names: Doxy-100, Monodox, Oracea, Targadox, Acticlate, Morgidox, Avidoxy, Doryx MPC, Mondoxyne NL, Dory;Dietary Supplement: Zinc<br>* 10 Day treatment<br>* Other names: Zinc sulphate;Dietary Supplement: Vitamin D3<br>* 10 day treatment<br>* Other names: cholecalciferol-D3;Dietary Supplement: Vitamin C<br>* 10 day treatment<br>* Other names: L-ascorbic acid;|
| Placebo Comparator: Placebo<br>Placebo and Vitamin D3, Vitamin C, and Zinc | Dietary Supplement: Zinc<br>* 10 Day treatment<br>* Other names: Zinc sulphate;Dietary Supplement: Vitamin D3<br>* 10 day treatment<br>* Other names: cholecalciferol-D3;Dietary Supplement: Vitamin C<br>* 10 day treatment<br>* Other names: L-ascorbic acid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Non-Infectivity by RT-PCR | Time to negative RT-PRC result indicating that patient is no longer infective | 6 months | 
| Time to Symptom progression in days as measured by NEWS scoring system (National Early Warning Score) | 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 | 
| Time to Symptom improvement as measured by NEWS scoring system (National Early Warning Score) | 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 as measured by Titer | Patients will have serum stored for titer testing to compare antibody levels over time | 6 months | 
| Efficacy of Treatment as measured by RT-PCR | Number of patients testing negative for SARS-CoV-2 by RT-PCR after 10 days of treatment | 10 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of Treatment as Measured by D-Dimer | Blood D-Dimer levels | 6 Months | 
| Safety of Treatment as Measured by Pro-Calcitonin | Blood Pro-Calcitonin levels | 6 Months | 
| Safety of Treatment as Measured by C-Reactive Protein | Blood CRP levels | 6 Months | 
| Safety of Treatment as Measured by Ferritin | Blood ferritin levels | 6 Months | 
| Safety of Treatment as Measured by Liver Enzymes | Blood enzyme levels | 6 Months | 
| Safety of Treatment as Measured by Complete Blood Count | CBC | 6 Months | 
| Safety of Treatment as Measured by Electrolyte Levels | Blood electrolytes | 6 Months | 
| Safety of Treatment as Measured by Treatment Related Adverse Events | Presence or absence of Grade 3 or high treatment related adverse events | 6 months |