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

NCT04370782 | Completed Phase 4 FDA Drug

• 1 other identifier: 20-21
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

COVID-19

Keywords

coronavirus; hydroxychloroquine; zinc sulfate

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (3)

• Severity of symptoms

  Day 5, Day 14, and Day 21

• Number of participants with adverse events due to drug regimen

  21 days

• Number of participants with QTc prolongation >500ms

  Days 1 thru 5, Day 10, Day 21

Study Arms (2)

Experimental Arm 1

EXPERIMENTAL

Hydroxychloroquine Azithromycin Zinc sulfate

Drug: Hydroxychloroquine; Drug: Azithromycin; Drug: Zinc Sulfate

Experimental Arm 2

EXPERIMENTAL

Hydroxychloroquine Doxycycline Zinc sulfate

Drug: Hydroxychloroquine; Drug: Zinc Sulfate; Drug: Doxycycline

Interventions

Hydroxychloroquine DRUG

Hydroxychloroquine 400mg twice a day (BID) on day 1, followed by 200mg BID for days 2-5

Experimental Arm 1; Experimental Arm 2

Azithromycin DRUG

Azithromycin 500mg on day 1, followed by 250mg once daily for days 2-5

Experimental Arm 1

Zinc Sulfate DRUG

Zinc sulfate 220mg once daily for 5 days

Experimental Arm 1; Experimental Arm 2

Doxycycline DRUG

Doxycycline 200 mg once daily for 5 days

Experimental Arm 2

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.)

Sponsors & Collaborators

• St. Francis Hospital, New York: lead

Study Sites (1)

St Francis Hospital

Roslyn, New York, 11576, United States

Location

Related Publications (15)

• Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, Shi Z, Hu Z, Zhong W, Xiao G. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020 Mar;30(3):269-271. doi: 10.1038/s41422-020-0282-0. Epub 2020 Feb 4. No abstract available.

  PMID: 32020029 BACKGROUND

• Yao X, Ye F, Zhang M, Cui C, Huang B, Niu P, Liu X, Zhao L, Dong E, Song C, Zhan S, Lu R, Li H, Tan W, Liu D. In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis. 2020 Jul 28;71(15):732-739. doi: 10.1093/cid/ciaa237.

  PMID: 32150618 BACKGROUND

• Devaux CA, Rolain JM, Colson P, Raoult D. New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19? Int J Antimicrob Agents. 2020 May;55(5):105938. doi: 10.1016/j.ijantimicag.2020.105938. Epub 2020 Mar 12.

  PMID: 32171740 BACKGROUND

• Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Mailhe M, Doudier B, Courjon J, Giordanengo V, Vieira VE, Tissot Dupont H, Honore S, Colson P, Chabriere E, La Scola B, Rolain JM, Brouqui P, Raoult D. RETRACTED: Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020 Jul;56(1):105949. doi: 10.1016/j.ijantimicag.2020.105949. Epub 2020 Mar 20.

  PMID: 32205204 BACKGROUND

• Kim AHJ, Sparks JA, Liew JW, Putman MS, Berenbaum F, Duarte-Garcia A, Graef ER, Korsten P, Sattui SE, Sirotich E, Ugarte-Gil MF, Webb K, Grainger R; COVID-19 Global Rheumatology Alliance. A Rush to Judgment? Rapid Reporting and Dissemination of Results and Its Consequences Regarding the Use of Hydroxychloroquine for COVID-19. Ann Intern Med. 2020 Jun 16;172(12):819-821. doi: 10.7326/M20-1223. Epub 2020 Mar 30. Erratum In: Ann Intern Med. 2020 Jun 16;172(12):844. doi: 10.7326/L20-0417.

  PMID: 32227189 BACKGROUND

• Wu C, Liu Y, Yang Y, Zhang P, Zhong W, Wang Y, Wang Q, Xu Y, Li M, Li X, Zheng M, Chen L, Li H. Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods. Acta Pharm Sin B. 2020 May;10(5):766-788. doi: 10.1016/j.apsb.2020.02.008. Epub 2020 Feb 27.

  PMID: 32292689 BACKGROUND

• Korant BD, Butterworth BE. Inhibition by zinc of rhinovirus protein cleavage: interaction of zinc with capsid polypeptides. J Virol. 1976 Apr;18(1):298-306. doi: 10.1128/JVI.18.1.298-306.1976.

  PMID: 176466 BACKGROUND

• Katz E, Margalith E. Inhibition of vaccinia virus maturation by zinc chloride. Antimicrob Agents Chemother. 1981 Feb;19(2):213-7. doi: 10.1128/AAC.19.2.213.

  PMID: 7347557 BACKGROUND

• Kumel G, Schrader S, Zentgraf H, Daus H, Brendel M. The mechanism of the antiherpetic activity of zinc sulphate. J Gen Virol. 1990 Dec;71 ( Pt 12):2989-97. doi: 10.1099/0022-1317-71-12-2989.

  PMID: 2177090 BACKGROUND

• Suara RO, Crowe JE Jr. Effect of zinc salts on respiratory syncytial virus replication. Antimicrob Agents Chemother. 2004 Mar;48(3):783-90. doi: 10.1128/AAC.48.3.783-790.2004.

  PMID: 14982765 BACKGROUND

• Eby GA, Davis DR, Halcomb WW. Reduction in duration of common colds by zinc gluconate lozenges in a double-blind study. Antimicrob Agents Chemother. 1984 Jan;25(1):20-4. doi: 10.1128/AAC.25.1.20.

  PMID: 6367635 BACKGROUND

• te Velthuis AJ, van den Worm SH, Sims AC, Baric RS, Snijder EJ, van Hemert MJ. Zn(2+) inhibits coronavirus and arterivirus RNA polymerase activity in vitro and zinc ionophores block the replication of these viruses in cell culture. PLoS Pathog. 2010 Nov 4;6(11):e1001176. doi: 10.1371/journal.ppat.1001176.

  PMID: 21079686 BACKGROUND

• Singh M, Das RR. Zinc for the common cold. Cochrane Database Syst Rev. 2013 Jun 18;(6):CD001364. doi: 10.1002/14651858.CD001364.pub4.

  PMID: 23775705 BACKGROUND

• Bao S, Knoell DL. Zinc modulates airway epithelium susceptibility to death receptor-mediated apoptosis. Am J Physiol Lung Cell Mol Physiol. 2006 Mar;290(3):L433-41. doi: 10.1152/ajplung.00341.2005. Epub 2005 Nov 11.

  PMID: 16284213 BACKGROUND

• Xue J, Moyer A, Peng B, Wu J, Hannafon BN, Ding WQ. Chloroquine is a zinc ionophore. PLoS One. 2014 Oct 1;9(10):e109180. doi: 10.1371/journal.pone.0109180. eCollection 2014.

  PMID: 25271834 BACKGROUND

MeSH Terms

Conditions

COVID-19; Coronavirus Infections

Interventions

Hydroxychloroquine; Azithromycin; Zinc Sulfate; Doxycycline

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals; Sulfates; Sulfuric Acids; Sulfur Acids; Sulfur Compounds; Inorganic Chemicals; Zinc Compounds; Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Study Officials

• Avni Thakore, MD

  Saint Francis Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 26, 2020
• First Posted: May 1, 2020
• Study Start: April 28, 2020
• Primary Completion: September 30, 2020
• Study Completion: September 30, 2020
• Last Updated: December 9, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)