New Antiviral Drugs for Treatment of COVID-19

- 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