COVID-19 Prophylaxis South Africa (COVER HCW)
Condition: Covid19; SARS-CoV Infection
MeSH terms: COVID-19; Severe Acute Respiratory Syndrome
Study type: Interventional
Phase: Phase 2

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.
    

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.
    

Intervention name(s): Nitazoxanide; Sofosbuvir/Daclatasvir
Intervention type(s): Drug; Drug
Intervention description(s): 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/daclatasvir 400mg/60 mg sofosbuvir/daclatasvir fixed dose combination 1 tablet daily
Intervention MeSH terms: Sofosbuvir; Nitazoxanide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Nitazoxanide; Sofosbuvir/Daclatasvir; COVID-19; SARS-CoV-2