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COVID-19 Prophylaxis South Africa (COVER HCW) (COVER)

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ClinicalTrials.gov Identifier: NCT04561063
Recruitment Status : Recruiting
First Posted : September 23, 2020
Last Update Posted : October 6, 2021
Sponsor:
Information provided by (Responsible Party):
Professor Francois Venter, University of Witwatersrand, South Africa

Brief 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. 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.

Condition or disease Intervention/treatment Phase
Covid19 SARS-CoV Infection Drug: Nitazoxanide Drug: Sofosbuvir/Daclatasvir Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1950 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
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
Actual Study Start Date : December 8, 2020
Estimated Primary Completion Date : February 28, 2022
Estimated Study Completion Date : February 28, 2022


Arm Intervention/treatment
No Intervention: Arm A: No pharmacological intervention (PPE only)
No intervention
Active Comparator: Arm B: Nitazoxanide (NTZ)
Nitozoxanide administered
Drug: Nitazoxanide
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.)

Active Comparator: Arm C: Sofosbuvir/daclatasvir (SOF/DCV).
Sofosbuvir/daclatasvir administered
Drug: Sofosbuvir/Daclatasvir
Sofosbuvir/daclatasvir 400mg/60 mg sofosbuvir/daclatasvir fixed dose combination 1 tablet daily




Primary Outcome Measures :
  1. Number of SARS-CoV-2 infections [ Time Frame: 6 months ]
    Number of SARS-CoV-2 infection (COVID-19) confirmed by PCR and/or serology.


Secondary Outcome Measures :
  1. Duration of symptoms [ Time Frame: 6 months ]
    Duration of symptoms for each symptomatic infection

  2. Maximum score on WHO Ordinal Scale [ Time Frame: 6 months ]
    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.

  3. Time to onset of SARS-CoV-2 infection [ Time Frame: 6 months ]
    Time to onset of SARS-CoV-2 infection (COVID-19) confirmed by PCR and/or serology

  4. Number of symptomatic SARS-CoV-2 infections [ Time Frame: 6 months ]
    Number of symptomatic SARS-CoV-2 infection (COVID-19) confirmed by PCR and/or serology

  5. Number of asymptomatic SARS-CoV-2 infections [ Time Frame: 6 months ]
    Number of asymptomatic • Asymptomatic SARS-CoV-2 infection suggested by serological outcome

  6. Peak score on modified Flu PRO [ Time Frame: 6 months ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Age ≥18 years of age, inclusive, at the time of signing the informed consent.
  2. Willing and able to provide informed consent via an electronic process.
  3. 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).
  4. 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.
  5. Body weight ≥45 kg.
  6. Access to reliable video conference, telephone, direct/text messaging, or other device permitting real-time, reliable information transfer.

Exclusion Criteria:

  1. Pregnant or lactating women.
  2. PCR and/or serology confirmed SARS-Cov-2 infection at screening.
  3. 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).
  4. 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)
    • Porphyria cutanea tarda.
  5. Currently on treatment for epilepsy or other seizure disorder.
  6. 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.
  7. Known hypersensitivity or specific contraindications to the use of any of the active drugs in the treatment arms or similar compounds.
  8. Current enrolment in another COVID-19 prevention trial.
  9. History of alcohol abuse within the last 6 months.
  10. Having history or have risk factors for brady-arrhythmias (those with undiagnosed cardiac conditions).
  11. History of malignancies in the last 5 years, excluding in-situ or non-invasive malignancies.
  12. Concurrent or recent (within 3 months) participation in other research with a compound likely to interfere with any of the investigational products.
  13. 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.
  14. Inability or unwillingness to be followed up for the study period.
  15. 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.)
  16. 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.
  17. Confirmed vaccination against SARS-Cov-2.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04561063


Contacts
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Contact: Simiso Sokhela 82 339 2322 ext +27 ssokhela@ezintsha.org

Locations
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South Africa
Charlotte Maxeke Johannesburg Academic Hospital Recruiting
Johannesburg, Gauteng, South Africa, 2196
Contact: Simiso Sokhela, MBBCh    +27823392322    ssokhela@ezintsha.org   
Contact: Nonkululeko Mashabane, BPharm    +27828253657    nmashabane@ezintsha.org   
Principal Investigator: Simiso Sokhela, MBBCh         
Sub-Investigator: Nomathemba Chandiwana, MBBCh         
Sub-Investigator: Joana Woods, MBBCh         
Sub-Investigator: Bronwyn Bosch, MBBCh         
Sub-Investigator: Karlien Moller, MBBCh         
Sub-Investigator: Esther Bhaskar, MBBCh         
Sub-Investigator: Ncomeka Manentsa, MBBCh         
Sub-Investigator: Chelsea Kruger, MBBCh         
Sunnyside Office Park Recruiting
Johannesburg, Gauteng, South Africa
Contact: Bronwyn Bosch, MBBCh    +27113585300    bbosch@ezintsha.org   
Contact: Godspower Akpomiemie, MPH    +2711358 5370    gakpomiemie@ezintsha.org   
Principal Investigator: Simiso Sokhela, MBBCh         
Sub-Investigator: Nomathemba Chandiwana, MBBCh         
Sub-Investigator: Joana Woods, MBBCh         
Sponsors and Collaborators
University of Witwatersrand, South Africa
Investigators
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Principal Investigator: Simiso Sokhela Ezintsha
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Professor Francois Venter, Divisional Director: Ezintsha, University of Witwatersrand, South Africa
ClinicalTrials.gov Identifier: NCT04561063    
Other Study ID Numbers: EZ-SS-025
First Posted: September 23, 2020    Key Record Dates
Last Update Posted: October 6, 2021
Last Verified: September 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Professor Francois Venter, University of Witwatersrand, South Africa:
Nitazoxanide
Sofosbuvir/Daclatasvir
COVID-19
SARS-CoV-2
Additional relevant MeSH terms:
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COVID-19
Severe Acute Respiratory Syndrome
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
Sofosbuvir
Nitazoxanide
Antiviral Agents
Anti-Infective Agents
Antiparasitic Agents