This exploratory study is a randomized, single center, open label study of four different experimental treatment arms versus standard of care for the treatment of SARS-CoV-2 infection in symptomatic outpatients with mild disease at the time of enrollment.
This phase 2, exploratory study will be an adaptive, randomized, open label, trial for treatment of individuals in an outpatient settings with mild SARS-CoV-2 infection. The primary outcome is focused on the evaluation of efficacy of the proposed experimental drugs in reducing upper respiratory viral shedding, defined as viral clearance (i.e., negative swab) on Day 7. Key secondary outcomes focus on other measures of viral shedding, safety evaluation, progression to LRTI (defined by resting blood oxygen saturation level \[SpO2\] \<93% sustained for two readings two hours apart and presence of subjective dyspnoea or cough), disease severity, clinical resolution rate, and cumulative incidence of hospitalization or mortality at Day 28.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
192
SOC - 2 tablets (1000 mg) to be taken 6-hourly as needed
SOC plus artesunate-amodiaquine (ASAQ) - 2 tablets (200/540 mg artesunate/amodiaquine) daily for 3 days
SOC plus pyronaridine-artesunate (PA) Weight 45 to \<65 kg: 3 tablets (540/180 mg pyronaridine/artesunate) daily for 3 days Weight ≥65 kg: 4 tablets (720/240 mg pyronaridine/artesunate) daily for 3 days
Ezintsha, Wits Reproductive Health & HIV Institute University of the Witwatersrand
Johannesburg, South Africa
Incidence of SARS-CoV-2 Clearance
Time frame: Day 7
Incidence of SARS-CoV-2 Clearance
Time frame: Day 3, 10, 14, 21, 28
Time to Clearance of Nasal SARS-CoV-2
Time frame: Day 0, 3, 7, 10, 14, 21, 28
Estimated Viral Load of SARS-CoV-2 Detected by Quantitative RT-PCR
baseline and day14, Day 14 value minus baseline value
Time frame: Day 14
Poisson Regression for Proportion of Days With Fever After Randomization
Time frame: Day 28
Percentage of Days With Respiratory Symptoms After Randomization
"Percentage of total study days in which participants experienced respiratory symptoms until day 28. Percentage calculated as (No. of days with respiratory symptoms) ÷ (No. of days observation) x 100"
Time frame: from randomization to end of study (until day 28)
FLU-PRO Plus Questionnaire Scores and FLU-PRO Plus Global Additional Daily Diary Items Over the First 14 Days
baseline and day 14, Day 14 value minus baseline value The FLU-PRO(inFLUenza Patient-Reported Outcome) Plus questionnaire was completed daily during the first 14 days, at Day 21 and at Day 28. From these items six domain scores for the body areas Nose, Throat, Eyes, Chest/Respiratory, Gastrointestinal, and Body/Systemic could be computed ranging from 0 (symptom free) to 4 (very severe symptoms). Total Score Range for FLU-PRO Plus * Score range per item: 0 (no symptoms) to 4 (very severe symptoms). A higher score indicates worse symptoms. * Total score calculation: The mean (average) of all item scores is used. (Minimum score: 0, Maximum score: 4)
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SOC plus favipiravir plus nitazoxanide (FPV-NTZ) Favipiravir: 1600 mg 12-hourly for 1 day then 600 mg 12-hourly for 6 days Nitazoxanide: 2 tablets (1000 mg) 12-hourly for 7 days
SOC plus sofosbuvir/daclatasvir (SOF/DCV) 1 tablet (400 mg/60 mg sofosbuvir/daclatasvir) daily for 7 days
Time frame: 14 days
Serious Adverse Events
Time frame: Day 28
Adverse Events
Time frame: Day 28
Related Adverse Events
Time frame: Day 28
LRTI
Time frame: Day 28
Maximum Score on WHO Ordinal Scale for Clinical Improvement During Study Participation
Time frame: Day 28
Cumulative Incidence of Hospitalization
Time frame: Day 28
Days of Hospitalization
Total number of hospitalization days for hospitalized participants in each group
Time frame: Day 28
Cumulative Incidence of Mortality, Measured at Day 28 or Later if Participant is Hospitalized at the Time of Day 28
Time frame: at Day 28 or later if participant is hospitalized at the time of Day 28 for up to 2 months