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

Phase 4

Completed

Interventions: Drug: Hydroxychloroquine
Drug: Zinc Sulfate
Drug: Azithromycin
Drug: Doxycycline

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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
Experimental Arm 2	Hydroxychloroquine	Hydroxychloroquine Doxycycline Zinc sulfate
Experimental Arm 2	Zinc Sulfate	Hydroxychloroquine Doxycycline Zinc sulfate
Experimental Arm 2	Doxycycline	Hydroxychloroquine Doxycycline Zinc sulfate
Experimental Arm 1	Hydroxychloroquine	Hydroxychloroquine Azithromycin Zinc sulfate
Experimental Arm 1	Azithromycin	Hydroxychloroquine Azithromycin Zinc sulfate
Experimental Arm 1	Zinc Sulfate	Hydroxychloroquine Azithromycin Zinc sulfate

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Severity of symptoms	Day 5, Day 14, and Day 21	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)
Number of participants with adverse events due to drug regimen	21 days	Number of participants with adverse events due to drug regimen
Number of participants with QTc prolongation >500ms	Days 1 thru 5, Day 10, Day 21	Assess all patients to evaluate for QTc prolongation \>500ms