Coronavirus InfectionPhase 4NCT04341493
Hydroxychloroquine vs Nitazoxanide in Patients With COVID-19
A Phase 4 study testing Nitazoxanide 500 MG and Hydroxychloroquine in people with Coronavirus Infection, run by Hugo Mendieta Zeron at 1 site in Mexico.
Trial summary
Coronaviruses (CoV) are positive-sense single-stranded RNA viruses that infect a wide range of hosts producing diseases ranging from the common cold to serious / fatal events. Nitazoxanide (NTZx) is a derivative of 5-nitrothiazole, synthesized in 1974 by Rosignol - Cavier. Read more about this study
- Who is it for?
- Ages 5 years and older
- Conditions the study is for
- Coronavirus Infection
- What is being tested?
- Nitazoxanide 500 MG and Hydroxychloroquine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 1 siteMexico
- Study dates
- 6 Apr 2020to 30 Dec 2020
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- COVID-19 positive patients
- Treated at the Health Institute of the State of Mexico (ISEM).
- With risk factors to get complicated: age more than 60 years old, diabetes mellitus or obesity grade II or more.
Who cannot join
- Patients who have inherent contraindications to each drug.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Treatment With Hydroxychloroquine vs Nitazoxanide + Hydroxychloroquine in Patients With COVID-19 With Risk Factors for Poor Outcome
Coronaviruses (CoV) are positive-sense single-stranded RNA viruses that infect a wide range of hosts producing diseases ranging from the common cold to serious / fatal events. Nitazoxanide (NTZx) is a derivative of 5-nitrothiazole, synthesized in 1974 by Rosignol - Cavier. NTZx has powerful antiviral effects through the phosphorylation of protein kinase activated by double-stranded RNA, which leads to an increase in phosphorylated factor 2-alpha, an intracellular protein with antiviral effects. The purpose of this study is to contrast the beneficial effect of NTZx vs NTZx plus hydroxychloroquine in patients Coronavirus Disease (COVID-19) as well as against other treatments.
Read the detailed description
Introduction The current pandemic caused by the SARS-COV2 coronavirus (COVID-19) is life-threatening and is challenging the world's best health systems. Accelerated spread of this pandemia led physicians to try a variety of treatments without a well established sequence due to ignorance about this new disease. The case fatality rate has been calculated at 2.2% but there are differences depending on the country affected.
Perspective When comparing the evolution of cases between Spain and Mexico, an apparently less pronounced trend is observed in Mexico, but this may be due to underdiagnosis. In calculations by the Mexican Ministry of Health, around 6% of the patients (approximately 10,500) who contract COVID-19 could be found serious and in need of hospitalization in intensive care.
NTZx NTZx and its circulating active metabolite, tizoxanide, inhibit the replication of a wide range of viruses, both RNA and DNA. It has action against 16 strains of Influenza A virus subtypes H1N1, H3N2, H3N2v, H3N8, H5N9, H7N1 and a strain of influenza B. It also works against respiratory syncytial virus, norovirus, dengue, yellow fever, Japanese encephalitis virus, rotavirus , hepatitis B and C, even against the human immunodeficiency virus (Severe Acute Respiratory Syndrome (SARS) and Middle East respiratory syndrome (MERS).
Problem Mexico is in Phase 2 according to the World Health Organization (WHO) and more local infections due to coronaviruses are expected. To date, various COVID-19 treatment schemes are being tested, but the usefulness of none can be assured.
When reviewing the drug schemes that are being carried out in the world, it calls the attention that developing countries are not included, beyond the fact that the tested alternatives are economically inaccessible.
This clinical survey aims to test the possible utility of NTZx against COVID-19, alone or in combination with hydroxychloroquine.
- Conditions
- Coronavirus Infection
- Being tested
- Nitazoxanide 500 MG, Hydroxychloroquine
- Keywords
- Treatment, Evolution
- Medical subject headings
- Coronavirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nitazoxanide 500 MGDrug
Also called hydroxychloroquine
Clinical evaluation of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using this option with two drugs
Clinical evaluation of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using this option with one drug
| Study group | Role | What they receive |
|---|---|---|
| Nitazoxanide + hydroxychloroquine | Experimental | Hydroxychloroquine 400 mg PO every 12 hours for two days and then 200 mg PO every 12 hours for four days + Nitazoxanide 500 mg PO every 6 hours for six days Receives: Drug: Nitazoxanide 500 MG; Drug: Hydroxychloroquine |
| Hydroxychloroquine | Active comparator | Hydroxychloroquine 200 mg PO every 12 hours for 7 days Receives: Drug: Hydroxychloroquine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mechanical ventilation requirement
Percentage of patients COVID-19 positive that required mechanical ventilation
Measured: Since the diagnosis until two weeks after
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2020
- Study start6 Apr 2020
- Primary completion30 Aug 2020
- Study completion30 Dec 2020
Why it stopped: Concerns about safety of Hydroxychloroquine
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Coronavirus InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- In this study all patients with a COVID-19 positive result attended at the Health Institute of the State of Mexico (ISEM), will be invited to participate and offered one of two options that try to reduce the complications of this disease.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hugo Mendieta Zeron
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Hugo Mendieta Zeron, Materno-Perinatal Hospital of the State of Mexico
- Investigators
- José Meneses Calderón, MD, Principal investigator, Hospital Materno-Perinatal "Mónica Pretelini Sáenz"Srivatsan Padmanabhan, MD, PhD, Principal investigator, St. Joseph Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04341493
- Sponsor's protocol ID
- 2020-03-681
- Status last verified
- Mar 2021
- First submitted
- 7 Apr 2020
- Last updated
- 1 Apr 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: If the final selected medical journal to send the paper of our research request it, we will add the full database of the studied population.
Publications
Rossignol JF. Nitazoxanide, a new drug candidate for the treatment of Middle East respiratory syndrome coronavirus. J Infect Public Health. 2016 May-Jun;9(3):227-30. doi: 10.1016/j.jiph.2016.04.001. Epub 2016 Apr 16.
PubMed 27095301Mo Y, Fisher D. A review of treatment modalities for Middle East Respiratory Syndrome. J Antimicrob Chemother. 2016 Dec;71(12):3340-3350. doi: 10.1093/jac/dkw338. Epub 2016 Sep 1.
PubMed 27585965Li H, Wang YM, Xu JY, Cao B. [Potential antiviral therapeutics for 2019 Novel Coronavirus]. Zhonghua Jie He He Hu Xi Za Zhi. 2020 Mar 12;43(3):170-172. doi: 10.3760/cma.j.issn.1001-0939.2020.03.004. Chinese.
PubMed 32164080Calderon JM, Zeron HM, Padmanabhan S. Treatment with Hydroxychloroquine vs Hydroxychloroquine + Nitazoxanide in COVID-19 patients with risk factors for poor prognosis: A structured summary of a study protocol for a randomised controlled trial. Trials. 2020 Jun 8;21(1):504. doi: 10.1186/s13063-020-04448-2.
PubMed 32513231
Study at a glance
From the registry record, last updated by the sponsor on 1 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment With Hydroxychloroquine vs Nitazoxanide + Hydroxychloroquine in Patients With COVID-19 With Risk Factors for Poor Outcome
- ClinicalTrials.gov ID
- NCT04341493
- Acronym / sponsor ID
- 2020-03-681
- Conditions
- Coronavirus Infection
- Keywords
- Treatment, Evolution
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Concerns about safety of Hydroxychloroquine
- Enrolment
- 44 participants (actual)
- Lead sponsor
- Hugo Mendieta ZeronUniversity, hospital or other
- Study start
- 6 Apr 2020 (actual)
- Primary completion
- 30 Aug 2020 (actual)
- Study completion
- 30 Dec 2020 (actual)
- First posted
- 10 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Coronaviruses (CoV) are positive-sense single-stranded RNA viruses that infect a wide range of hosts producing diseases ranging from the common cold to serious / fatal events. Nitazoxanide (NTZx) is a derivative of 5-nitrothiazole, synthesized in 1974 by Rosignol - Cavier. NTZx has powerful antiviral effects through the phosphorylation of protein kinase activated by double-stranded RNA, which leads to an increase in phosphorylated factor 2-alpha, an intracellular protein with antiviral effects. The purpose of this study is to contrast the beneficial effect of NTZx vs NTZx plus hydroxychloroquine in patients Coronavirus Disease (COVID-19) as well as against other treatments.
Detailed description
Introduction The current pandemic caused by the SARS-COV2 coronavirus (COVID-19) is life-threatening and is challenging the world's best health systems. Accelerated spread of this pandemia led physicians to try a variety of treatments without a well established sequence due to ignorance about this new disease. The case fatality rate has been calculated at 2.2% but there are differences depending on the country affected.
Perspective When comparing the evolution of cases between Spain and Mexico, an apparently less pronounced trend is observed in Mexico, but this may be due to underdiagnosis. In calculations by the Mexican Ministry of Health, around 6% of the patients (approximately 10,500) who contract COVID-19 could be found serious and in need of hospitalization in intensive care.
NTZx NTZx and its circulating active metabolite, tizoxanide, inhibit the replication of a wide range of viruses, both RNA and DNA. It has action against 16 strains of Influenza A virus subtypes H1N1, H3N2, H3N2v, H3N8, H5N9, H7N1 and a strain of influenza B. It also works against respiratory syncytial virus, norovirus, dengue, yellow fever, Japanese encephalitis virus, rotavirus , hepatitis B and C, even against the human immunodeficiency virus (Severe Acute Respiratory Syndrome (SARS) and Middle East respiratory syndrome (MERS).
Problem Mexico is in Phase 2 according to the World Health Organization (WHO) and more local infections due to coronaviruses are expected. To date, various COVID-19 treatment schemes are being tested, but the usefulness of none can be assured.
When reviewing the drug schemes that are being carried out in the world, it calls the attention that developing countries are not included, beyond the fact that the tested alternatives are economically inaccessible.
This clinical survey aims to test the possible utility of NTZx against COVID-19, alone or in combination with hydroxychloroquine.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- In this study all patients with a COVID-19 positive result attended at the Health Institute of the State of Mexico (ISEM), will be invited to participate and offered one of two options that try to reduce the complications of this disease.
| Arm | Type | Receives |
|---|---|---|
| Nitazoxanide + hydroxychloroquine | Experimental | Drug: Nitazoxanide 500 MG, Drug: HydroxychloroquineHydroxychloroquine 400 mg PO every 12 hours for two days and then 200 mg PO every 12 hours for four days + Nitazoxanide 500 mg PO every 6 hours for six days |
| Hydroxychloroquine | Active comparator | Drug: HydroxychloroquineHydroxychloroquine 200 mg PO every 12 hours for 7 days |
Who may qualify
- Ages
- 5 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- COVID-19 positive patients
- Treated at the Health Institute of the State of Mexico (ISEM).
- With risk factors to get complicated: age more than 60 years old, diabetes mellitus or obesity grade II or more.
Key exclusion criteria (1 listed)
- Patients who have inherent contraindications to each drug.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nitazoxanide 500 MGAlso: hydroxychloroquineClinical evaluation of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using this option with two drugs | Drug | Nitazoxanide + hydroxychloroquine |
| HydroxychloroquineClinical evaluation of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using this option with one drug | Drug | Hydroxychloroquine, Nitazoxanide + hydroxychloroquine |
Primary outcome
Mechanical ventilation requirement
Time frame: Since the diagnosis until two weeks after
Percentage of patients COVID-19 positive that required mechanical ventilation
Results and safety
The study was stopped early (reason given: Concerns about safety of Hydroxychloroquine). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2021.
- Background: PubMed 27095301Rossignol JF. Nitazoxanide, a new drug candidate for the treatment of Middle East respiratory syndrome coronavirus. J Infect Public Health. 2016 May-Jun;9(3):227-30. doi: 10.1016/j.jiph.2016.04.001. Epub 2016 Apr 16.
- Background: PubMed 27585965Mo Y, Fisher D. A review of treatment modalities for Middle East Respiratory Syndrome. J Antimicrob Chemother. 2016 Dec;71(12):3340-3350. doi: 10.1093/jac/dkw338. Epub 2016 Sep 1.
- Background: PubMed 32164080Li H, Wang YM, Xu JY, Cao B. [Potential antiviral therapeutics for 2019 Novel Coronavirus]. Zhonghua Jie He He Hu Xi Za Zhi. 2020 Mar 12;43(3):170-172. doi: 10.3760/cma.j.issn.1001-0939.2020.03.004. Chinese.
- Derived from this study: PubMed 32513231Calderon JM, Zeron HM, Padmanabhan S. Treatment with Hydroxychloroquine vs Hydroxychloroquine + Nitazoxanide in COVID-19 patients with risk factors for poor prognosis: A structured summary of a study protocol for a randomised controlled trial. Trials. 2020 Jun 8;21(1):504. doi: 10.1186/s13063-020-04448-2.
- Individual participant dataSharing planned: Yes. If the final selected medical journal to send the paper of our research request it, we will add the full database of the studied population.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
José Meneses Calderón, MD principal investigator
Hospital Materno-Perinatal "Mónica Pretelini Sáenz"
Srivatsan Padmanabhan, MD, PhD principal investigator
St. Joseph Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Nitazoxanide 500 MG and Hydroxychloroquine in people with Coronavirus Infection, run by Hugo Mendieta Zeron at 1 site in Mexico.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 1 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Mexico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Concerns about safety of Hydroxychloroquine). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mechanical ventilation requirement (time frame: Since the diagnosis until two weeks after). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04341493, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Apr 2021.