A Study of Efficacy and Safety of Azvudine vs. Nirmatrelvir-Ritonavir in the Treatment of COVID-19 Infection

A Prospective Multicenter, Randomized, Controlled Clinical Trial of the Safety and Efficacy of Azvudine vs. Nirmatrelvir-Ritonavir in Hospitalized Patients With Moderate to Severe COVID-19 Infection

The COVID-19 pandemic has become a major public health challenge, and the treatment options for the disease are currently limited. The commonly used oral small-molecule anti-COVID-19 drugs in China are Nirmatrelvir-Ritonavir and Azvudine. These drugs have been tested in pre-marketing clinical trials in patients with non-severe COVID-19 infection and have demonstrated therapeutic effects in inhibiting virus transmission and preventing disease progression. However, until now, the efficacy and safety of these drugs in patients with moderate to severe COVID-19 infections remains unclear. Therefore, this study is aiming to compare the efficacy and safety of Azvudine and Nirmatrelvir-Ritonavir in moderate to severe COVID-19 infections. This study will be a multicenter, randomized, controlled clinical trial study in patients hospitalized with moderate to severe COVID-19 infections. Recovery of clinical symptoms, nucleic acid negative conversion, improvement in oxygenation index, and imaging improvement will be used as study endpoints.

Study Overview

• Status: Recruiting
• Conditions: COVID-19
• Intervention / Treatment: Drug: Azvudine; Drug: Nirmatrelvir-Ritonavir

• Study Type: Interventional
• Enrollment (Anticipated): 410
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Bing Leng; Phone Number: +86531-68776461; Email: taozilb@163.com
• Study Contact Backup: Name: Chengwu Shen; Phone Number: +86531-68778252; Email: scw810@163.com

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China
      • Recruiting
      • Shandong Provincial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Hospitalized patients of ≥18 years old, regardless of gender or race;
2. Patients who have a positive SARS-CoV-2 test result;

3. Diagnosed with moderate or severe COVID-19 infection according to the diagnostic criteria from the "Diagnosis and treatment program trial version 10 guidelines" issued by the National Health Commission of the People's Republic of China. Including:

   ①Moderate: continuous high fever for more than 3 days or/and cough, shortness of breath, etc., but the breathing frequency (RR) is less than 30 times/minute, and the oxygen saturation when inhaling air at rest is > 93%. Imaging shows the characteristic manifestations of COVID-19 pneumonia.

   ② Severe: Adults meet any of the following requirements: A, shortness of breath, RR≥ 30 times/minute; B, the oxygen saturation when inhaling air at rest is ≤ 93%; C, Arterial partial oxygen pressure (PaO2)/ Fraction of inspiration O2 (FiO2) ≤300mmHg (1mmHg=0.133kPa), and PaO2/FiO2 should be corrected according to the following formula for areas above 1000 m :PaO2/FiO2× [760/ atmospheric pressure (mmHg)]; D, the clinical symptoms were gradually aggravated, and the lung imaging showed that the lesion progressed significantly within 24 ~ 48 hours > 50%.

4. Join this study voluntarily.
5. Each subject must sign an informed consent form (ICF) indicating that he/she understands the purpose and procedure of the study and is willing to participate in the study. Considering the patient's condition, the ICF may be signed by the legal representative.

Exclusion Criteria:

1. Allergic to the drugs involved;
2. Pregnancy or lactation;
3. Diagnosed or suspected critical COVID-19 infection;
4. Child-Pugh C of liver function or estimated glomerular filtration rate (eGFR) less than 30mL/min during screening;
5. Receive SARS-CoV-2 monoclonal antibody therapy or other antiviral therapy;
6. The subject and/or authorized family members refused to receive anti-COVID-19 treatment;
7. Any life-threatening disease or organ system dysfunction that the researcher thinks can harm the safety of the subjects and expose the research results to unnecessary risks; drug addicts, uncontrolled mental illness or cognitive dysfunction.
8. Join other similar clinical researchers within 3 months;
9. Patients who were not considered suitable for inclusion by the researchers (such as patients who were expected to be unable to adhere to the treatment due to financial problems).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Azvudine	Drug: Azvudine; 5mg orally, once a day, for no more than 14 days
Active Comparator: Nirmatrelvir-Ritonavir	Drug: Nirmatrelvir-Ritonavir; Nirmatrelvir 300mg combined with Ritonavir 100mg every 12 hours for 5 days. For patients with 30≤ eGFR < 60 ml/min, it should be reduced to150mg/100mg Nirmatrelvir-Ritonavir every 12 hours for 5 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time and proportion of patients with COVID-19 infection to have sustained clinical recovery	Up to 28 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Time and proportion of the nucleic acid negative conversion	Days 3, 6, 9, 12, 15, 18, 21, 24, 27
Time and proportion of chest CT image improvement	Days 6, 12, 18, 24
Time and proportion of oxygenation index improvement	Up to 28 days
Length of stay	Up to 28 days
Proportion of progression to critical COVID-19 and death from any cause	Up to 28 days
Time of COVID-19 related symptom score and World Health Organization (WHO) clinical progress scale score. Time and proportion of clinical recovery, symptom resolution and regression of major symptoms	Up to 28 days

Collaborators and Investigators

• Sponsor: Shandong Provincial Hospital
• Collaborators: Gansu Provincial Hospital; The Affiliated Hospital Of Southwest Medical University; Rizhao People's Hospital; The Second Affiliated Hospital of Shandong First Medical University; Central hospital Affiliated to Shandong First Medical University

Study record dates

Study Major Dates

• Study Start (Actual): January 21, 2023
• Primary Completion (Anticipated): May 21, 2023
• Study Completion (Anticipated): July 21, 2023

Study Registration Dates

• First Submitted: January 20, 2023
• First Submitted That Met QC Criteria: January 20, 2023
• First Posted (Actual): January 25, 2023

Study Record Updates

• Last Update Posted (Estimate): February 27, 2023
• Last Update Submitted That Met QC Criteria: February 24, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Safety; Efficacy; COVID-19; Azvudine; Nirmatrelvir-Ritonavir
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Ritonavir
• Other Study ID Numbers: SWYX2023022

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No