New Antiviral Drugs for Treatment of COVID-19

September 1, 2020 updated by: Hatem Elalfy, Mansoura University

Effect of a Combination of Nitazoxanide, Ribavirin and Ivermectin Plus Zinc Supplement on the Clearance of COVID-19: a Pilot Sequential Clinical Trial

Background: In December 2019, SARS-CoV-2 was isolated on Vero E6 and Huh7 cell lines after an outbreak of pneumonia of unknown origin in Wuhan, Hubei Province, China. Since the basis for pathogenesis of this virus and its proliferation is unclear, there is still no definitive treatment or vaccine against it. Thus, medications used against SARS-CoV-2 are mainly based on their effectiveness on in vitro studies, virtual screenings and records of their effects on earlier strains of coronavirus, SARS and MERS. Therefore, the immediate introduction of potential COVID-19 treatments can be essential and salvaging. Aim: to compare the rate and time of viral clearance in subjects receiving the combination of Nitazoxanide, Ribavirin and Ivermectin vs. those control group (without any intervention). Methods: a sequential clinical trial in this design sample size is not fixed in advance. Instead data will be evaluated as they are collected, and further sampling is will be stopped in accordance with a pre-defined stopping rule as soon as significant results are observed. After "n" (10 subjects in each group) subjects in each group are available an interim analysis will be conducted. A statistical test will be performed to compare the two groups and if the null hypothesis is rejected the trial is terminated; otherwise, the trial continues, another n subjects per group will be recruited, and the statistical test is performed again, including all subjects. If the null is rejected, the trial is terminated, and otherwise it continues with periodic evaluations until a maximum number of interim analyses have been performed, at which point the last statistical test is conducted and the trial is discontinued [25]. Outcome: The combination of Nitazoxanide, Ribavirin, Ivermectin and Zinc could be effective in clearance of COVID 19.

KEY WOARD: COVID-19; clinical trial; corona virus

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

  • Research Design and Methodologies:

This search will focus on patients with COVID 19 infection this study is a prospective cohort study based on the analysis of response in comparative panel between two arm Nitazoxanide, Ribavirin and Ivermectin plus Zinc arm and other arm without any intervention as regards the safety and efficacy and cost effective result. Two years duration of the project would be enough to cover the stages of the work as shown below in the time plan. Initial stage of collecting materials and patients' clinical data, each patient will undergoes strict follow up period to reveal the clinical, laboratory and radiological response. The procedures are to be approved by the institutional ethical committee.

Study Design:

After obtaining informed consent from the subjects and IRB approval from Mansoura Faculty of Medicine.

Technical Design:

The proposed study will be hospital- based cross- sectional study.

Data collection tools and techniques:

1-Clinical work package: The aim of the Tropical Department in Mansoura University within WP1 is to implement surveillance, diagnostic and monitoring models for the disease management of patients with COVID 19 infection according to the current scientific evidence. They will evaluate the clinical usefulness of the application of therapeutic clinical trial, to improve the disease outcomes and reduce the costs of the disease burdens.

In brief, the approach will consist of the following steps:

  1. Diagnosis of patient with COVID 19 infection by swab and PCR testing
  2. Tailored therapeutic strategy in patients with COVID 19 infection undergoing treatment by nitazoxanide, Ribavirin and Ivermectin plus Zinc (this done in collaboration with biochemical department and Clinical Pathology department in Mansoura University).
  3. Patients with the other group will not undergoes any intervention.
  4. Specific laboratory analysis for COVID 19 RNA by Polymerase Chain Reaction in nasopharyngeal and oropharyngeal swabs will be don't to both groups.
  5. Monitoring the treatment response in the follow up periods.

Description of work and role of participants:

Rationale of study: COVID-19 is an emerging infection with relatively high transmission rate from healthy carriers to their contacts. There is no known drug that eliminate the virus from the nasopharynx.

Study objectives: to compare the rate and time of viral clearance in subjects receiving the combination of Nitazoxanide, Ribavirin and Ivermectin vs. those control group (without any intervention) Study hypothesis: The combination of Nitazoxanide, Ribavirin, Ivermectin plus zinc supplement have higher rate of viral clearance at earlier time than the control group

Population and methods:

  • Study locality: subject with proven COVID-infection admitted to quarantine centers of Mansoura University Hospitals
  • Study design: a sequential clinical trial in this design sample size is not fixed in advance. Instead data will be evaluated as they are collected, and further sampling is will be stopped in accordance with a pre-defined stopping rule as soon as significant results are observed. After "n" (10 subjects in each group) subjects in each group are available an interim analysis will be conducted. A statistical test will be performed to compare the two groups and if the null hypothesis is rejected the trial is terminated; otherwise, the trial continues, another n subjects per group will be recruited, and the statistical test is performed again, including all subjects. If the null is rejected, the trial is terminated, and otherwise it continues with periodic evaluations until a maximum number of interim analyses have been performed, at which point the last statistical test is conducted and the trial is discontinued [25].
  • Target population: any subject with COVID-19 PCR positive pharyngeal swab and referred to the above-mentioned quarantine without any comorbidities and no sensitivity or contraindication to the three drugs.
  • Sample size: will depends on sequential analysis until a significant effect will be detected with a maximum of 100 subjects in each arm.
  • Randomization: subjects will be allocated to either arm by block randomization method with sealed opaque envelops. Each block will include 10 subjects (to be allocated randomly as 5 in each group)
  • Intervention:

A) Treatment group: will receive a combination of Nitazoxanide, Ribavirin and Ivermectin B) Control group: will not receive nothing

  • Data collection will include: sociodemographic data, clinical history, results of follow up (daily or according to clinical situation )

  • Follow-up: to record any side effects of drugs, swab will be taken for PCR

    2-Laboratory and investigational work package:

The patients are subjected to following laboratory workup:

Task 2-1: basic laboratory serum analysis for the following parameters: transaminases (AST, ALT), albumin, bilirubin, prothrombin time, complete blood picture, renal assessment (creatinine or clearance if needed), CRP, Oxygen saturation

Task 2-2: specific laboratory analysis ( if available case by case ):

Serum samples from each patient are collected for analysis at different time for detection of ferritin, triglycerides, LDH,

3-Invetigational radiology work package:

This package includes chest x ray and /or high resolution CT

Study Type

Interventional

Enrollment (Anticipated)

100

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Egypt
    • Select A State Or Province
      • Mansoura, Select A State Or Province, Egypt, 35516
        • Mansoura University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • any subject with COVID-19 PCR positive pharyngeal swab and referred to the above-mentioned quarantine without any comorbidities and no sensitivity or contraindication to the three drugs.

Exclusion Criteria:

  • PATIENTS WITH COMORBIDITY :ISCHEMIC HEART DISEASES,OR KNOWN HYPERSENSITIVITY TO THE DRUGS

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: INTERVENTION

*Intervention:

A) Treatment group: will receive a combination of Nitazoxanide, Ribavirin and Ivermectin for a duration of seven days :
Drug: Treatment group: will receive a combination of Nitazoxanide, Ribavirin and Ivermectin for a duration of seven days :

Target population: any subject with COVID-19 PCR positive pharyngeal swab and referred to the above-mentioned quarantine without any comorbidities and no sensitivity or contraindication to the three drugs.

  • Sample size: will depends on sequential analysis until a significant effect will be detected with a maximum of 100 subjects in each arm.
  • Randomization: subjects will be allocated to either arm by block randomization method with sealed opaque envelops. Each block will include 10 subjects (to be allocated randomly as 5 in each group)
  • Intervention:

A) Treatment group: will receive a combination of Nitazoxanide, Ribavirin and Ivermectin for a duration of seven days

Other Names:
  • Nanozoxide, ivermectin and ribavirin 200 mg or 400 mg
No Intervention: CONTROL

B) Control group: will not receive nothing

  • Data collection will include: sociodemographic data, clinical history, results of follow up (daily or according to clinical situation )
  • Follow-up: to record any side effects of drugs, swab will be taken for PCR

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
negative test result for COVID-19
Time Frame: 2 YEARS
PCR FOR COVID-19 will be done on serial visits till turn to negative, first after 5 day then serial every 48 hours till become negative for two consecutive samples.
2 YEARS

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mansoura University

Investigators

  • Principal Investigator: HATEM ELALFY, MD, PROFESSOR OF ENDEMIC MEDICINE DEPARTMENT
  • Principal Investigator: HATEM ELALFY, MD, Mansoura University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

October 1, 2020

Primary Completion (Anticipated)

May 1, 2022

Study Completion (Anticipated)

May 1, 2022

Study Registration Dates

First Submitted

May 12, 2020

First Submitted That Met QC Criteria

May 14, 2020

First Posted (Actual)

May 18, 2020

Study Record Updates

Last Update Posted (Actual)

September 3, 2020

Last Update Submitted That Met QC Criteria

September 1, 2020

Last Verified

September 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20.05.69

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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Clinical Trials on Treatment group: will receive a combination of Nitazoxanide, Ribavirin and Ivermectin for a duration of seven days :

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