A Multicenter Randomized Double-blind Placebo-controlled Study to Investigate Azvudine in Symptomatic Adult Participants With COVID-19 Who Are at Increased Risk of Progressing to Severe Illness
Trial Snapshot
- Phase
- Phase 2
- Status
- Recruiting
- Enrollment
- 1,096
- Locations
- 1
- Primary Endpoint
- Proportion of COVID-19-related critical illness or all-cause death within 28 days.
Study Overview
Brief Summary
To investigate whether treatment with Azvudine reduces the risk of severe illness or death in patients who are at a potential risk of progressing to severe COVID-19 infection.
Detailed Description
The study is designed as a randomized, parallel, double-blind, placebo-controlled trial, in which all participants will be randomized to a test group or control group in a 1:1 ratio.
The test group will be given Azvudine in combination with conventional therapy excluding anti-viral therapy and observed for efficacy. The control group will be given placebo in combination with conventional therapy excluding anti-viral therapy and observed for efficacy.
Test Group will recruit 548 participants who will be given Azvudine + conventional therapy other than antiviral*5 mg/day, oral, up to 7 days (1 mg/tablet).
Control Group will recruit 548 who will be given Placebo + conventional therapy other than antiviral* 5 tablets/day, oral, up to 7 days.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
Randomized, Double-blind, Placebo-controlled Study
Eligibility Criteria
- Ages
- 18 Years to 120 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •(1) An age of 18 years or over (inclusive); (2) Not more than five days since the development of COVID-19 symptoms, and positive for nucleic acid or antigen test for COVID-19 within five days before enrollment; (3) Presence of at least one symptom related to COVID-19 infection at the time of enrollment; (4) Agreement to practice effective birth control (for females of child-bearing potential); (5) Presence of at least one high risk factor for severe COVID-19 infection:
- •Age ≥ 60 years;
- •Fever (body temperature ≥ 38℃) for ≥ 3 days;
- •Current smokers (still being smoking within 30 days before enrollment and have used at least 100 cigarettes up to date);
- •Immunosuppressive diseases, including but not limited to: myelosuppression or organ transplantation or primary immunodeficiency disease; prolonged use of immunosuppressive agents (≥ 20 mg/d for at least 14 days in the case of prednisone within the last 30 days); biologic therapy (such as infliximab, etc.); use of immunomodulators (including but not limited to methotrexate, azathioprine, etc.); radiotherapy and/or chemotherapy for any malignancies within 90 days (for chest radiotherapy, this time interval should be more than 6 months);
- •Chronic lung disease (such as asthma requiring intervention daily, bronchiectasis, COPD, pulmonary hypertension, OSAS, interstitial lung disease, etc.);
- •Hypertension; ⑧ Cardiovascular diseases (previously diagnosed as myocardial infarction or stroke, TIA (transient ischemic attack), cardiac insufficiency, angina pectoris requiring nitrate therapy, CABG, post-PCI, post-carotid endarterectomy and aortic bypass surgery, etc.);
- •⑨ Type 1 or type 2 diabetes;
- •⑩ Neurodevelopmental abnormalities (such as cerebral palsy, Down's syndrome) or other genetic or metabolic syndromes and severe congenital malformations;
- •⑪ Active tumors (excluding localized skin cancer);
- •⑫ No vaccination against COVID-19
Exclusion Criteria
- •(1) Known or suspected allergy to the components of Azvudine Tablets; (2) Patients diagnosed as severe or critical COVID-19 infection (Severe:
- •shortness of breath with RR ≥ 30 breaths/min;
- •oxygen saturation ≤ 93% when inhaling air at rest;
- •partial pressure of arterial oxygen (PaO2) / fraction of inspired oxygen (FiO2) ≤ 300 mmHg;
- •progressive worsening of clinical symptoms, and obvious lesion progression > 50% on lung images within 24 to 48 hours. Critical:
- •respiratory failure, requiring mechanical ventilation;
- •concomitant organ failure, requiring care in ICU); (3) Patients with severe liver disease (total bilirubin [TBIL] ≥ 2 × upper limit of normal (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≥ 3 × ULN; (4) Patients with severe renal insufficiency (glomerular filtration rate ≤ 60 mL/min/1.73 m2) or currently on continuous renal replacement therapy, hemodialysis, and/or peritoneal dialysis; (5) Patients with malabsorption syndrome or any other condition compromising gastrointestinal absorption, or patients requiring parenteral nutrition or with difficulty in taking the investigational product orally; (6) Known HIV infection; (7) Presence of diabetic ketosis or hyperosmolar hyperglycemic state (HHS); (8) Total neutrophil count < 750 cells/L; (9) Pregnant or lactating women or those who plan to have a child during participation in this study and within six months after the end of this study; (10) Currently participating in another clinical trial or currently using another investigational product; (11) Presence of other active infections (must be etiologically confirmed) in addition to COVID-19 infection; (12) Presence of any comorbidities requiring hospitalization and/or a surgical procedure within 7 days prior to the start of this study or a comorbidity considered life-threatening within 30 days prior to the start of this study; (13) Patients who have received or are expected to receive convalescent plasma for COVID-19; (14) Previous treatment with anti-viral agents that have been proved to be effective against COVID-19, including but not limited to Nirmatrelvir/Ritonavir or Molnupiravir (this criterion does not apply to use of glucocorticoids for reasons other than COVID-19); (15) Other conditions that make it inappropriate for the participant to take part in this trial at the investigator's discretion.
Arms & Interventions
Azvudine
Azvudine in Patients at Potential Risk of Progressing to Severe COVID-19 Infection
Intervention: Azvudine (Drug)
Placebo
Placebo in Patients at Potential Risk of Progressing to Severe COVID-19 Infection
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Proportion of COVID-19-related critical illness or all-cause death within 28 days.
Time Frame: 28 days
Proportion of COVID-19-related critical illness or all-cause death within 28 days. COVID-19-related critical illness is defined as: a patient with an SpO2 of 90% to 95% requiring high-flow oxygen inhalation with a fraction of inspired oxygen (FiO2) not less than 60% or requiring non-invasive ventilation with a FiO2 not less than 60%; or requiring mechanical ventilation or ECMO for organ support.
Secondary Outcomes
- Incidence rates of Azvudine-related adverse events and serious adverse events(28 days)
- Days of hospitalization and ICU stay(28 days)
- Duration of COVID-19-related symptoms(14 days)
- All-cause death(6 months)
- COVID-19 viral load in pharyngeal swabs(D1, D3, D7)