Hydroxychloroquine and Zinc With Either Azithromycin or Doxycycline for Treatment of COVID-19 in Outpatient Setting

Study Overview
=================
Brief Summary
-----------------
This is a randomized, open-label trial to assess the safety and efficacy of hydroxychloroquine, and zinc in combination with either azithromycin or doxycycline in a higher risk COVID-19 positive outpatient population.

Detailed Description
-----------------
COVID-19 is an aggressive and contagious virus, found to have high mortality especially in persons with comorbidities (Age>60, hypertension [HTN], diabetes mellitus [DM], Cancer, and otherwise immunocompromised). Zinc is a supplement with possible antiviral properties, having been shown to have effect in the common cold, many of which are due to coronavirus. In addition, elderly patients and patients with co-morbidities have high incidence of zinc deficiency. We are repleting zinc in all patients and studying its direct effect in combination with hydroxychloroquine, and an antibiotic, either azithromycin or doxycycline to see if there is enhanced treatment efficacy in early COVID-19 infection and assess the safety of these two regimen.

Official Title
-----------------
A Randomized Study Evaluating the Safety and Efficacy of Hydroxychloroquine and Zinc in Combination With Either Azithromycin or Doxycycline for the Treatment of COVID-19 in the Outpatient Setting

Conditions
-----------------
COVID-19

Intervention / Treatment
-----------------
* Drug: Hydroxychloroquine
* Drug: Azithromycin
* Drug: Zinc Sulfate
* Drug: Doxycycline


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Able to read and understand informed consent. High initial clinical suspicion by physician based on signs and symptoms (fever, cough, myalgias, fatigue, shortness of breath) followed by RT-PCR for confirmation of COVID-19 diagnosis Any gender Age 60 years and older Age 30-59 years with one or more of the following: abnormal lung exam abnormal oxygen staturation <95% abnormal chest x-ray or chest CT persistent fever >100.4 degrees Fahrenheit upon arrival to Emergency department (ED) one of the following co-morbidities: hypertension, diabetes mellitus, history of coronary artery disease, chronic kidney disease (CKD), asthma, chronic obstructive pulmonary disease, current or former smoker, or morbid obesity (Body Mass Index ≥35) Exclusion Criteria: Pregnant or breastfeeding female Severe COVID-19 requiring admission for inpatient treatment Need for any oxygen supplementation Need for mechanical ventilatory support History of oxygen supplementation dependency History of cancer with ongoing chemotherapy or radiation therapy Concurrent antimicrobial therapy Known hypersensitivity to hydroxychloroquine or other 4-aminoquinoline compounds Already taking hydroxychloroquine or chloroquine within 1 month Known G6-PD deficiency History of retinopathy History of current cardiac diseases (heart failure, ventricular arrhythmias, Left bundle branch block and/or Right bundle branch block, QTc prolongation >480ms), or family history of sudden cardiac death Ongoing use of drugs that prolong the QTc interval (antipsychotics, antidepressants, class I and III antiarrhythmics, triptans) Severe renal disease: glomerular filtration rate (GFR) <30ml/min Severe hepatic impairment (elevated total bilirubin >2 mg/dL, decreased albumin <2.8 g/dL, signs of jaundice and ascites.) Active alcohol abuse (>5 drinks per day or >20 drinks per week.) Seizure disorder, currently on medications Known hypersensitivity to any tetracyclines.

Ages Eligible for Study
-----------------
Minimum Age: 30 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Arm 1<br>Hydroxychloroquine Azithromycin Zinc sulfate | Drug: Hydroxychloroquine<br>* Hydroxychloroquine 400mg twice a day (BID) on day 1, followed by 200mg BID for days 2-5<br>Drug: Azithromycin<br>* Azithromycin 500mg on day 1, followed by 250mg once daily for days 2-5<br>Drug: Zinc Sulfate<br>* Zinc sulfate 220mg once daily for 5 days<br>|
| Experimental: Experimental Arm 2<br>Hydroxychloroquine Doxycycline Zinc sulfate | Drug: Hydroxychloroquine<br>* Hydroxychloroquine 400mg twice a day (BID) on day 1, followed by 200mg BID for days 2-5<br>Drug: Zinc Sulfate<br>* Zinc sulfate 220mg once daily for 5 days<br>Drug: Doxycycline<br>* Doxycycline 200 mg once daily for 5 days<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Resolution of Symptoms relative to baseline (day 1 of trial) | Patients will be assessed on day 5 for when COVID-19 symptoms completely resolve compared to baseline (day 1 of trial) | Day 5 | 
| Time to Resolution of Symptoms relative to baseline (day 1 of trial) | Patients will be assessed on day 14 for when COVID-19 symptoms completely resolve compared to baseline (day 1 of trial) | Day 14 | 
| Time to Resolution of Symptoms relative to baseline (day 1 of trial) | Patients will be assessed on day 21 for when COVID-19 symptoms completely resolve compared to baseline (day 1 of trial) | Day 21 | 
| Number of participants hospitalized and/or requiring repeat ER visits | Number of participants hospitalized and/or requiring repeat ER visits related to COVID-19 complications | 21 days | 
| ICU Length of Stay | If hospitalized, number of participants admitted to the ICU, and number of days in the ICU | Until Discharged up to 30 days | 
| Ventilator | If placed on ventilator, number of days on a ventilator | Until extubated up to 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severity of symptoms | Severity of symptoms evaluated at day 5, day 14, and day 21 scored by the participant for feverishness, sore throat, cough, shortness of breath, myalgias. (0 =none; 1 = mild; 2 = moderate; 3 = severe) | Day 5, Day 14, and Day 21 | 
| Number of participants with adverse events due to drug regimen | Number of participants with adverse events due to drug regimen | 21 days | 
| Number of participants with QTc prolongation >500ms | Assess all patients to evaluate for QTc prolongation >500ms | Days 1 thru 5, Day 10, Day 21 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
coronavirus, hydroxychloroquine, zinc sulfate