Clinical Trials Logo

Clinical Trial Details — Status: Not yet recruiting

Administrative data

NCT number NCT04392427
Other study ID # 20.05.69
Secondary ID
Status Not yet recruiting
Phase Phase 3
First received
Last updated
Start date October 2020
Est. completion date May 2022

Study information

Verified date September 2020
Source Mansoura University
Contact HATEM ELALFY, MD
Phone +201224790518
Email ELALFY2004@MANS.EDU.EG
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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


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


Recruitment information / eligibility

Status Not yet recruiting
Enrollment 100
Est. completion date May 2022
Est. primary completion date May 2022
Accepts healthy volunteers No
Gender All
Age group 12 Years and older
Eligibility 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 Design


Related Conditions & MeSH terms


Intervention

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

Locations

Country Name City State
Egypt Mansoura University Mansoura Select A State Or Province

Sponsors (1)

Lead Sponsor Collaborator
Mansoura University

Country where clinical trial is conducted

Egypt, 

References & Publications (5)

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. — View Citation

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. Review. — View Citation

Graci JD, Cameron CE. Mechanisms of action of ribavirin against distinct viruses. Rev Med Virol. 2006 Jan-Feb;16(1):37-48. Review. — View Citation

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. Review. — View Citation

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 — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary negative test result for COVID-19 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
See also
  Status Clinical Trial Phase
Terminated NCT04558125 - Low-Dose Tenecteplase in Covid-19 Diagnosed With Pulmonary Embolism Phase 4
Recruiting NCT04410510 - P2Et Extract in the Symptomatic Treatment of Subjects With COVID-19 Phase 2/Phase 3
Active, not recruiting NCT04420676 - Synbiotic Therapy of Gastrointestinal Symptoms During Covid-19 Infection N/A
Completed NCT04419025 - Efficacy of N-Acetylcysteine (NAC) in Preventing COVID-19 From Progressing to Severe Disease Phase 2
Completed NCT04425317 - Detection of SARS-CoV-2 in Follicular Fluid and Cumulus-oocyte-complexes in COVID-19 Patients N/A
Completed NCT04395911 - Safety and Efficacy of SCD in AKI or ARDS Patients Associated With COVID-19 Infections N/A
Withdrawn NCT04456426 - Characteristics of Patients With COVID-19 in Meta State, Colombia
Completed NCT04526769 - Detecting SARS-CoV-2 in Tears
Suspended NCT04385771 - Cytokine Adsorption in Patients With Severe COVID-19 Pneumonia Requiring Extracorporeal Membrane Oxygenation N/A
Completed NCT04425720 - Use of Remote Monitoring for COVID-19 Patient N/A
Completed NCT04419610 - RAS and Coagulopathy in COVID19 Early Phase 1
Completed NCT04546581 - Inpatient Treatment of COVID-19 With Anti-Coronavirus Immunoglobulin (ITAC) Phase 3
Completed NCT04435327 - Lung Damage Caused by SARS-CoV-2 Pneumonia (COVID-19)
Terminated NCT04530448 - Coronavirus Induced Acute Kidney Injury: Prevention Using Urine Alkalinization Phase 4
Not yet recruiting NCT04524156 - COVID-19 : Transcutaneous pO2 and pCO2 as Predictive Factors for Acute Respiratory Destress Syndrome in Patients Affected With SARS-Cov-2 N/A
Completed NCT04441710 - Caregiver Serological Monitoring Extended Secondarily to Patients With the SARS-CoV-2 Coronavirus
Completed NCT04357834 - WAVE. Wearable-based COVID-19 Markers for Prediction of Clinical Trajectories
Terminated NCT04614025 - Open-label Multicenter Study to Evaluate the Efficacy of PLX-PAD for the Treatment of COVID-19 Phase 2
Completed NCT04402957 - LSALT Peptide vs. Placebo to Prevent ARDS and Acute Kidney Injury in Patients Infected With SARS-CoV-2 (COVID-19) Phase 2
Recruiting NCT04397705 - Remote Monitoring of Cancer Patients With Suspected Covid-19 Phase 1