Covid19Phase 2COVERNCT04561063
COVID-19 Prophylaxis South Africa (COVER HCW)
A Phase 2 study testing Nitazoxanide and Sofosbuvir/Daclatasvir in people with Covid19 and SARS-CoV Infection, run by University of Witwatersrand, South Africa at 2 sites in South Africa.
Trial summary
This is a randomised, multi-center, open label, adaptive, exploratory trial to assess the efficacy of two different drug regimens in terms of preventing symptomatic COVID-19 disease in healthcare workers at high risk of exposure to SARS-CoV-2. Read more about this study
- Who is it for?
- Ages 18 to 99 yearsHealthy volunteers can take part
- Conditions the study is for
- Covid19, SARS-CoV Infection
- What is being tested?
- Nitazoxanide and Sofosbuvir/Daclatasvir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,950 participants
- Where
- 2 sitesSouth Africa
- Study dates
- 8 Dec 2020to 28 Feb 2022
- Phase
- Phase 2
- 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 18 to 99 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age ≥18 years of age, inclusive, at the time of signing the informed consent.
- Willing and able to provide informed consent via an electronic process.
- Healthcare worker employed at a participating institution that has been identified as high-risk for SARS-CoV-2 exposure (may include doctors, nurses, nurse aids, radiographers, physiotherapists, phlebotomists, technicians, porters, cleaners, laboratory or other personnel identified as being at high risk of exposure), CHW involved in the collection of samples for the identification of SARS-CoV-2 through PCR, and inner city inhabitants at high risk for SARS-CoV-2 exposure due to the nature of their work and frequent use of public transport (may include essential services employees such as fire fighters, law enforcement officers, grocery store employees; and non healthcare workers using public transport at least three times a week).
- Women of reproductive potential must be using a highly effective method of contraception prior to enrolment or must be willing to start a method at enrolment and continue its use throughout the duration of the study.
- Body weight ≥45 kg.
- Access to reliable video conference, telephone, direct/text messaging, or other device permitting real-time, reliable information transfer.
Who cannot join
- Pregnant or lactating women.
- PCR and/or serology confirmed SARS-Cov-2 infection at screening.
- Current symptoms of COVID-19 disease (including, but not limited to, fever or chills, cough, myalgia, sore throat, shortness of breath, or new onset of anosmia or ageusia, or diarrhea).
- Self-reported presence or history of any of the following conditions:
- Chronic kidney disease (Stage IV or receiving dialysis)
- Cirrhosis (Child-Pugh Class B or greater)
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- Porphyria cutanea tarda.
- Currently on treatment for epilepsy or other seizure disorder.
- Currently on treatment with a protease inhibitor-based antiretroviral regimen, or efavirenz, or on treatment with amiodarone, carbamazepine, phenobarbitone, phenytoin, primidone, rifampicin,St. John's wort or any herbal products which may potentially decrease the concentration of the IMP.
- Known hypersensitivity or specific contraindications to the use of any of the active drugs in the treatment arms or similar compounds.
- Current enrolment in another COVID-19 prevention trial.
- History of alcohol abuse within the last 6 months.
- Having history or have risk factors for brady-arrhythmias (those with undiagnosed cardiac conditions).
- History of malignancies in the last 5 years, excluding in-situ or non-invasive malignancies.
- Concurrent or recent (within 3 months) participation in other research with a compound likely to interfere with any of the investigational products.
- Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the safety of the volunteer or the objectives of the study. The Investigator should make this determination in consideration of the volunteer's medical history.
- Inability or unwillingness to be followed up for the study period.
- Personnel (e.g. investigator, sub-investigator, research assistant, pharmacist, study coordinator or anyone mentioned in the delegation log) directly involved in the conduct of the study. (Personnel employed at a study site, but not directly involved in the conduct of the study, who would like to participate in the study, may only do so if they are enrolled in the study through a different site at which they are not employed.)
- Participant is judged by the Investigator to be at significant risk of failing to comply with the provisions of the protocol as to cause harm to self or seriously interfere with the validity of the study results.
- Confirmed vaccination against SARS-Cov-2.
Trial locations and contacts
2 sites in 1 country.
South Africa2 sites
Charlotte Maxeke Johannesburg Academic Hospital
Johannesburg, Gauteng, 2196
Sunnyside Office Park
Johannesburg, Gauteng
About this study
Official title: A Multi-center, Randomised, Open Label Study of Nitazoxanide (NTZ), or Sofosbuvir and Daclatasvir (SOF/DCV), Compared to no Pharmacological Intervention for the Prevention of COVID-19 Disease in Healthcare Workers and Inner City Inhabitants at High Risk of Exposure to SARS-CoV-2
This is a randomised, multi-center, open label, adaptive, exploratory trial to assess the efficacy of two different drug regimens in terms of preventing symptomatic COVID-19 disease in healthcare workers at high risk of exposure to SARS-CoV-2. The trial will compare two different experimental medication arms to the control arm comprising the use of standard personal protective equipment (PPE) with no additional pharmacological intervention.
Read the detailed description
This is a randomised, multi-center, open label, adaptive, exploratory trial to assess the efficacy of two different drug regimens in terms of preventing symptomatic COVID-19 disease in healthcare workers at high risk of exposure to SARS-CoV-2. The trial will compare two different experimental medication arms to the control arm comprising the use of standard personal protective equipment (PPE) with no additional pharmacological intervention.
Volunteers will be recruited from participating institutions and community healthcare workers (CHWs) that are responsible for collecting swabs for PCR detection of SARS-CoV-2. Up to 1950 (or 2130 pending funding) eligible participants will be randomised in a 1:1:1 ratio to one of the investigational arms.
Participants will be followed until 65 PCR and serology-confirmed, SARS-CoV-2 infections are identified in the control arm (or 165 in the entire study cohort). For each episode of PCR-confirmed COVID-19 disease, data on self-reported symptoms (modified Flu-PRO) and their duration, and an investigator-assessed severity score (WHO Ordinal Scale for Clinical Improvement) will be recorded. Data on self-reported symptoms and duration will also be collected for other all-cause acute respiratory illnesses. Safety and tolerability of each arm will be assessed through adverse event reporting. Participants who develop COVID-19 disease will have their IMP discontinued but will be followed up in the study until the completion of the trial, where possible. Multiple, discrete occurrences of COVID-19 disease could therefore be identified in a single participant.
Additional arms may be added, or existing ones substituted, should new potential agents be identified or other combinations for prophylaxis be proposed. A formal amendment will be documented should this be considered.
- Conditions
- Covid19, SARS-CoV Infection
- Being tested
- Nitazoxanide, Sofosbuvir/Daclatasvir
- Keywords
- Nitazoxanide, Sofosbuvir/Daclatasvir, COVID-19, SARS-CoV-2
- Medical subject headings
- COVID-19, Severe Acute Respiratory Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NitazoxanideDrug
Nitozoxanide 1 tablet (500 mg) taken 12-hourly with food for the first week, followed by 2 tablets (1000 mg) taken 12-hourly with food thereafter. (Participants that fail to tolerated the 1000 mg 12-hourly dose may revert back to the lower dose.)
Sofosbuvir/DaclatasvirDrug
Sofosbuvir/daclatasvir 400mg/60 mg sofosbuvir/daclatasvir fixed dose combination 1 tablet daily
| Study group | Role | What they receive |
|---|---|---|
| Arm A: No pharmacological intervention (PPE only) | No intervention | No intervention |
| Arm B: Nitazoxanide (NTZ) | Active comparator | Nitozoxanide administered Receives: Drug: Nitazoxanide |
| Arm C: Sofosbuvir/daclatasvir (SOF/DCV). | Active comparator | Sofosbuvir/daclatasvir administered Receives: Drug: Sofosbuvir/Daclatasvir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of SARS-CoV-2 infections
Number of SARS-CoV-2 infection (COVID-19) confirmed by PCR and/or serology.
Measured: 6 months
Secondary outcomes (6)
Duration of symptoms
Duration of symptoms for each symptomatic infection
Measured: 6 months
Maximum score on WHO Ordinal Scale
Maximum score on WHO Ordinal Scale for Clinical Improvement for each symptomatic infection. Score of 0 being uninfected and a score of 8 being dead.
Measured: 6 months
Time to onset of SARS-CoV-2 infection
Time to onset of SARS-CoV-2 infection (COVID-19) confirmed by PCR and/or serology
Measured: 6 months
Number of symptomatic SARS-CoV-2 infections
Number of symptomatic SARS-CoV-2 infection (COVID-19) confirmed by PCR and/or serology
Measured: 6 months
Number of asymptomatic SARS-CoV-2 infections
Number of asymptomatic • Asymptomatic SARS-CoV-2 infection suggested by serological outcome
Measured: 6 months
Peak score on modified Flu PRO
Peak score on modified Flu-PRO during each symptomatic infection. 37-item questionairre assessing the severity of flu like symptoms one a scale of 0 - not at all to 5 - very much.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2020
- Study start8 Dec 2020
- Primary completion28 Feb 2022
- Study completion28 Feb 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Covid19Studies 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 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,950 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Witwatersrand, South Africa
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Professor Francois Venter, University of Witwatersrand, South Africa
- Investigators
- Simiso Sokhela, Principal investigator, Ezintsha
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04561063
- Sponsor's protocol ID
- EZ-SS-025
- Acronym
- COVER
- Status last verified
- Jun 2022
- First submitted
- 21 Sep 2020
- Last updated
- 7 Jun 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.
PubMed 34473343
Study at a glance
From the registry record, last updated by the sponsor on 7 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-center, Randomised, Open Label Study of Nitazoxanide (NTZ), or Sofosbuvir and Daclatasvir (SOF/DCV), Compared to no Pharmacological Intervention for the Prevention of COVID-19 Disease in Healthcare Workers and Inner City Inhabitants at High Risk of Exposure to SARS-CoV-2
- ClinicalTrials.gov ID
- NCT04561063
- Acronym / sponsor ID
- COVER / EZ-SS-025
- Conditions
- Covid19, SARS-CoV Infection
- Keywords
- Nitazoxanide, Sofosbuvir/Daclatasvir, COVID-19, SARS-CoV-2
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,950 participants (actual)
- Lead sponsor
- University of Witwatersrand, South AfricaUniversity, hospital or other
- Study start
- 8 Dec 2020 (actual)
- Primary completion
- 28 Feb 2022 (actual)
- Study completion
- 28 Feb 2022 (actual)
- First posted
- 23 Sep 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.
This is a randomised, multi-center, open label, adaptive, exploratory trial to assess the efficacy of two different drug regimens in terms of preventing symptomatic COVID-19 disease in healthcare workers at high risk of exposure to SARS-CoV-2. The trial will compare two different experimental medication arms to the control arm comprising the use of standard personal protective equipment (PPE) with no additional pharmacological intervention.
Detailed description
This is a randomised, multi-center, open label, adaptive, exploratory trial to assess the efficacy of two different drug regimens in terms of preventing symptomatic COVID-19 disease in healthcare workers at high risk of exposure to SARS-CoV-2. The trial will compare two different experimental medication arms to the control arm comprising the use of standard personal protective equipment (PPE) with no additional pharmacological intervention.
Volunteers will be recruited from participating institutions and community healthcare workers (CHWs) that are responsible for collecting swabs for PCR detection of SARS-CoV-2. Up to 1950 (or 2130 pending funding) eligible participants will be randomised in a 1:1:1 ratio to one of the investigational arms.
Participants will be followed until 65 PCR and serology-confirmed, SARS-CoV-2 infections are identified in the control arm (or 165 in the entire study cohort). For each episode of PCR-confirmed COVID-19 disease, data on self-reported symptoms (modified Flu-PRO) and their duration, and an investigator-assessed severity score (WHO Ordinal Scale for Clinical Improvement) will be recorded. Data on self-reported symptoms and duration will also be collected for other all-cause acute respiratory illnesses. Safety and tolerability of each arm will be assessed through adverse event reporting. Participants who develop COVID-19 disease will have their IMP discontinued but will be followed up in the study until the completion of the trial, where possible. Multiple, discrete occurrences of COVID-19 disease could therefore be identified in a single participant.
Additional arms may be added, or existing ones substituted, should new potential agents be identified or other combinations for prophylaxis be proposed. A formal amendment will be documented should this be considered.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm A: No pharmacological intervention (PPE only) | No intervention | –No intervention |
| Arm B: Nitazoxanide (NTZ) | Active comparator | Drug: NitazoxanideNitozoxanide administered |
| Arm C: Sofosbuvir/daclatasvir (SOF/DCV). | Active comparator | Drug: Sofosbuvir/DaclatasvirSofosbuvir/daclatasvir administered |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age ≥18 years of age, inclusive, at the time of signing the informed consent.
- Willing and able to provide informed consent via an electronic process.
- Healthcare worker employed at a participating institution that has been identified as high-risk for SARS-CoV-2 exposure (may include doctors, nurses, nurse aids, radiographers, physiotherapists, phlebotomists, technicians, porters, cleaners, laboratory or other personnel identified as being at high risk of exposure), CHW involved in the collection of samples for the identification of SARS-CoV-2 through PCR, and inner city inhabitants at high risk for SARS-CoV-2 exposure due to the nature of their work and frequent use of public transport (may include essential services employees such as fire fighters, law enforcement officers, grocery store employees; and non healthcare workers using public transport at least three times a week).
- Women of reproductive potential must be using a highly effective method of contraception prior to enrolment or must be willing to start a method at enrolment and continue its use throughout the duration of the study.
- Body weight ≥45 kg.
Key exclusion criteria (20 listed)
- Pregnant or lactating women.
- PCR and/or serology confirmed SARS-Cov-2 infection at screening.
- Current symptoms of COVID-19 disease (including, but not limited to, fever or chills, cough, myalgia, sore throat, shortness of breath, or new onset of anosmia or ageusia, or diarrhea).
- Self-reported presence or history of any of the following conditions:
- Currently on treatment for epilepsy or other seizure disorder.
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 |
|---|---|---|
| NitazoxanideNitozoxanide 1 tablet (500 mg) taken 12-hourly with food for the first week, followed by 2 tablets (1000 mg) taken 12-hourly with food thereafter. (Participants that fail to tolerated the 1000 mg 12-hourly dose may revert back to the lower dose.) | Drug | Arm B: Nitazoxanide (NTZ) |
| Sofosbuvir/DaclatasvirSofosbuvir/daclatasvir 400mg/60 mg sofosbuvir/daclatasvir fixed dose combination 1 tablet daily | Drug | Arm C: Sofosbuvir/daclatasvir (SOF/DCV). |
Primary outcome
Number of SARS-CoV-2 infections
Time frame: 6 months
Number of SARS-CoV-2 infection (COVID-19) confirmed by PCR and/or serology.
6 secondary outcomes
Duration of symptoms
Time frame: 6 months
Maximum score on WHO Ordinal Scale
Time frame: 6 months
Time to onset of SARS-CoV-2 infection
Time frame: 6 months
Number of symptomatic SARS-CoV-2 infections
Time frame: 6 months
Number of asymptomatic SARS-CoV-2 infections
Time frame: 6 months
Peak score on modified Flu PRO
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jun 2022.
- Derived from this study: PubMed 34473343Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.
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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.
Simiso Sokhela principal investigator
Ezintsha
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nitazoxanide and Sofosbuvir/Daclatasvir in people with Covid19 and SARS-CoV Infection, run by University of Witwatersrand, South Africa at 2 sites in South Africa.
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 6 inclusion and 20 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: finished, as of the sponsor's last update on 7 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in South Africa. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Number of SARS-CoV-2 infections (time frame: 6 months). 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 NCT04561063, which also lists 1 linked publication.
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 7 Jun 2022.