PHRU CoV01 A Trial of Triazavirin (TZV) for the Treatment of Mild-moderate COVID-19 — PHRUCov01  

Covid19 Clinical Trial

Official title: A Pragmatic, Individually Randomised, Double-blind, Placebo-controlled Trial of Triazavirin (TZV) for the Treatment of Mild-moderate SARS-CoV-2 Infection A Phase II and III Clinical Trial

Status Terminated

Clinical Trial Summary

A) Phase II: Early viral responses to triazavirin In hospitalised patients with mild-moderate COVID-19, in addition to standard of care therapy, treatment with triazavirin 250mg three times daily for five days, the slope of increase of the Ct values of serial nasopharyngeal swabs to 12 days after initiation of treatment will be ≥24% higher than in hospitalised patients receiving standard of care treatment only.

B) Phase III: Efficacy of triazavirin to improve clinical outcomes In hospitalised patients with mild-moderate laboratory proven COVID-19, in addition to standard of care therapy, treatment with triazavirin 250mg three times daily for five days will reduce a composite outcome - death; ICU admission or mechanical ventilation; or prolonged duration of admission- by ≥29% when compared to the composite outcome in hospitalised patients receiving standard of care therapy only.

Clinical Trial Description

Design: This will be a two-site, iterative, double-blinded, randomized, placebo controlled, 2-arm, phase II and III superiority trial. Participants will be randomised 1:1 to each arm. The first part of the trial will recruit 64 evaluable patients to validate a biological effect of triazavirin on SARS-CoV-2. If triazavirin indeed has a demonstrable effect, the trial will continue to randomise another 316 evaluable participants to ascertain if there is a clinical benefit.

Participants: Three hundred and eighty evaluable patients with newly diagnosed, laboratory confirmed, mild-moderate (including asymptomatic) SARS-CoV-2 infection. Men and women will be recruited in a ratio of 3:2.

Study sites: Tshepong Provincial Hospitals in NW Province. Field Hospitals in Gauteng (NASREC) and North West (West Vaal) will be included if possible.

Study Duration: Follow up will be approximately 32 days; the total duration of from recruitment of first patients to last follow follow up visit is 15 months.

Population: Adult in-patients, ≥18 years and older, with a recent diagnostic test positive for SARS-CoV-2. Men and women will be recruited, in a ratio of 3:2.

Intervention: After verbal informed consent is provided, participants will be randomly assigned to receive either five days of triazavirin 250mg p.o three times daily, or placebo at the same dosing schedule, in addition to standard of care therapy prescribed by the attending physicians.

Primary Objectives:

To ascertain whether a 5-day course of TZV (250mg taken orally three times per day) in addition to standard of care treatment for in-patients with mild-moderate disease caused by SARS-Cov-2 is effective in:

A. Enhancing the rate of viral clearance from the nasopharynx compared to placebo.

B. To demonstrate a favourable outcome in the intervention arm compared to placebo arm using a composite clinical outcome that consists of the earliest occurrence of any of the following:

1. Death

2. Admission to ICU or mechanical ventilation required (continuous positive airway pressure, high flow nasal oxygen or intubation);

3. Prolonged duration of admission lasting >14 days (this includes patients who are discharged and re-admitted within 48 hours of leaving the hospital).

C. To ascertain safety and tolerability of the investigational drug TZV

Secondary objectives:

1. To compare time to the first of two consecutive nasopharyngeal swabs that are negative for SARS-CoV-2 between the arms.

2. To compare the proportion of participants whose nasopharyngeal swabs are negative for SARS-CoV-2 two days after the end of study treatment.

3. To compare symptom reduction and improvement in clinical measures between arms

4. To compare efficacy of nasopharyngeal swabs with salivary specimens in assessing viral responses to treatment. ;

Related Conditions & MeSH terms

• COVID-19
• Covid19

• NCT number: NCT04581915
• Study type: Interventional
• Source: Wits Health Consortium (Pty) Ltd
• Status: Terminated
• Phase: Phase 2/Phase 3
• Start date: September 8, 2020
• Completion date: April 20, 2021