New Antiviral Drugs for Treatment of COVID-19

NCT ID: NCT04392427

Last Updated: 2020-09-03

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-31
• Study Completion Date: 2022-05-31

Brief Summary

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

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

Conditions

COVID; Drug Effect

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

INTERVENTION

*Intervention:

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

Group Type: ACTIVE_COMPARATOR

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

Intervention Type: DRUG

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

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

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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

Intervention Type: DRUG

Other Intervention Names

Nanozoxide, ivermectin and ribavirin 200 mg or 400 mg

Eligibility Criteria

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

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mansoura University

OTHER

Sponsor Role: lead

Responsible Party

Hatem Elalfy

Professor of Tropical Medicine and Hepatogastroenterology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

HATEM ELALFY, MD

Role: PRINCIPAL_INVESTIGATOR

PROFESSOR OF ENDEMIC MEDICINE DEPARTMENT

HATEM ELALFY, MD

Role: PRINCIPAL_INVESTIGATOR

Mansoura University

Locations

Mansoura University

Al Mansurah, Select A State Or Province, Egypt

Countries

Egypt

Central Contacts

HATEM ELALFY, MD

Role: CONTACT

ELALFY2004@MANS.EDU.EG

+201224790518

TAREK BESHEER, MD

Role: CONTACT

TAREKBESHEER@YAHOO.COM

0122797705

Facility Contacts

HATEM ELALFY

Role: primary

elalfy_hatem66@yahoo.com

01224790518

References

Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, Zhao X, Huang B, Shi W, Lu R, Niu P, Zhan F, Ma X, Wang D, Xu W, Wu G, Gao GF, Tan W; China Novel Coronavirus Investigating and Research Team. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020 Feb 20;382(8):727-733. doi: 10.1056/NEJMoa2001017. Epub 2020 Jan 24.

Reference Type: RESULT

PMID: 31978945 (View on PubMed)

Cui J, Li F, Shi ZL. Origin and evolution of pathogenic coronaviruses. Nat Rev Microbiol. 2019 Mar;17(3):181-192. doi: 10.1038/s41579-018-0118-9.

Reference Type: RESULT

PMID: 30531947 (View on PubMed)

Rossignol JF. Nitazoxanide: a first-in-class broad-spectrum antiviral agent. Antiviral Res. 2014 Oct;110:94-103. doi: 10.1016/j.antiviral.2014.07.014. Epub 2014 Aug 7.

Reference Type: RESULT

PMID: 25108173 (View on PubMed)

Graci JD, Cameron CE. Mechanisms of action of ribavirin against distinct viruses. Rev Med Virol. 2006 Jan-Feb;16(1):37-48. doi: 10.1002/rmv.483.

Reference Type: RESULT

PMID: 16287208 (View on PubMed)

Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM. The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Res. 2020 Jun;178:104787. doi: 10.1016/j.antiviral.2020.104787. Epub 2020 Apr 3.

Reference Type: RESULT

PMID: 32251768 (View on PubMed)

Other Identifiers

20.05.69

Identifier Type: -

Identifier Source: org_study_id