Placebo Controlled Trial to Evaluate Zinc for the Treatment of COVID-19 in the Outpatient Setting

• ClinicalTrials.gov Identifier: NCT04621461
• Recruitment Status: Completed
• First Posted: November 9, 2020
• Last Update Posted: February 11, 2021
• Sponsor: St. Francis Hospital, New York
• Information provided by (Responsible Party): St. Francis Hospital, New York

Study Description

Brief Summary:

This is a randomized, double-blind, placebo-controlled trial to assess the efficacy of zinc in a higher risk COVID-19 positive outpatient population.

Condition or disease	Intervention/treatment	Phase
Corona Virus Infection	Dietary Supplement: Zinc Sulfate 220 MG; Drug: Placebo	Phase 4

Detailed Description:

Zinc, a micronutrient, appears to have anti-viral properties with various mechanisms of action depending on the concentration Zinc supplementation has been reviewed extensively for use in the common cold, and has been shown to reduce the duration of symptoms. In-vitro studies have shown zinc can inhibit RNA-dependent RNA polymerase (RdRP) in coronavirus, which is typically a conserved region in the viral genome. In-vitro experiments have also shown that lung epithelium in a zinc depleted state can become susceptible to apoptosis and loss of barrier function, increasing permeability, which can lead to acute respiratory distress syndrome (ARDS).

If a patient can travel to St. Francis Hospital they can have a COVID test on site at a designated St. Francis testing location. The COVID test will be resulted via a rapid Covid (Point of Care device) or at a local lab.

Patients who are unable to travel to St. Francis Hospital or one of the outpatient practices, will be allowed to enroll remotely. Patients are eligible to enroll within 72 hours of a positive Covid-19 test result. Study medications will be mailed to the patient overnight after being enrolled.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 3 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Intervention Model Description: This is a randomized, double-blind, placebo-controlled trial to assess the efficacy of zinc in a higher risk COVID-19 positive outpatient population. Patients will randomized to zinc or placebo.
• Masking: Double (Participant, Investigator)
• Masking Description: Patients will be randomized via a randomization block. Only the research coordinator will know which group the patients belong to. Placebo pills given to the patient will be similar in size and shape to zinc.
• Primary Purpose: Treatment
• Official Title: A Randomized, Placebo-Controlled Study Evaluating the Efficacy of Zinc for the Treatment of COVID-19 in the Outpatient Setting
• Actual Study Start Date: December 20, 2020
• Actual Primary Completion Date: February 8, 2021
• Actual Study Completion Date: February 8, 2021

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Experimental Arm #1; Placebo	Drug: Placebo; Once daily for 5 days
Experimental: Experimental Arm #2; Zinc sulfate	Dietary Supplement: Zinc Sulfate 220 MG; 220mg once daily for 5 days

Outcome Measures

Primary Outcome Measures :

1. Number of participants hospitalized and/or requiring repeat emergency room visits [ Time Frame: 21 days ]
   COVID-19 related complications that require the participant to be hospitalized or have an emergency room visit
2. Number of participants admitted to the Intensive care unit (ICU) [ Time Frame: 30 days ]
   If hospitalized, number of participants admitted to the ICU, and number of days in the ICU
3. Number of participants on a ventilator [ Time Frame: 30 days ]
   If placed on ventilator, number of days on a ventilator

Secondary Outcome Measures :

1. All-cause mortality [ Time Frame: Up to 30 days ]
   Total number of deaths in the cohort.
2. Time to resolution of COVID-19 symptoms [ Time Frame: Evaluated at day 2, 6, day 14, and day 21 ]
   Time at which the patient is completely symptom free.
3. Severity of symptoms [ Time Frame: Evaluated at day 2, 6, 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)

Eligibility Criteria

• Ages Eligible for Study: 30 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 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 saturation <95%
  • abnormal Chest X-ray or chest CT
  • persistent fever >100.4 degrees Fahrenheit
  • one of the following co-morbidities: hypertension, diabetes mellitus, history of coronary artery disease, chronic kidney disease (CKD), asthma, COPD, current or former smoker, or morbid obesity (Body Mass Index ≥35)

Exclusion Criteria:

• 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
• Known hypersensitivity to zinc
• Severe renal disease: Glomerular Filtration Rate <30ml/min

Contacts and Locations

Locations

United States, New York

St. Francis Hospital - The Heart Center

Roslyn, New York, United States, 11576

Sponsors and Collaborators

St. Francis Hospital, New York

Investigators

• Principal Investigator: Avni Thakore, MD; St. Francis Hospital - The Heart Center

More Information

Publications:

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.

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.

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.

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.

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.

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.

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.

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

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.

• Responsible Party: St. Francis Hospital, New York
• ClinicalTrials.gov Identifier: NCT04621461
• Other Study ID Numbers: 20-19
• First Posted: November 9, 2020
• Last Update Posted: February 11, 2021
• Last Verified: February 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by St. Francis Hospital, New York:

COVID-19; Zinc

Additional relevant MeSH terms:

COVID-19; Coronavirus Infections; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Zinc Sulfate; Astringents; Physiological Effects of Drugs; Dermatologic Agents