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.
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.
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.)
Drug: Sofosbuvir/Daclatasvir
Sofosbuvir/daclatasvir 400mg/60 mg sofosbuvir/daclatasvir fixed dose combination 1 tablet daily
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.
Charlotte Maxeke Johannesburg Academic Hospital
Johannesburg, Gauteng, South Africa
Sunnyside Office Park
Johannesburg, Gauteng, South Africa
Simiso Sokhela, Principal Investigator
Ezintsha