Evaluation of Ganovo （Danoprevir ） Combined With Ritonavir in the Treatment of SARS-CoV-2 Infection

Study Overview
=================
Brief Summary
-----------------
Evaluation of the efficacy and safety of Ganovo combined with ritonavir for patients infected with SARS-CoV-2.

Detailed Description
-----------------
Given no specific antiviral therapies for new coronavirus pneumonia approved yet and Ganovo, an oral Hepatitis C virus protease inhibitor, approved in China in June 2018 , this open, controlled trial will evaluate the efficacy and safety of Ganovo in hospitalized patients infected with SARS-CoV-2.

Official Title
-----------------
An Open Clinical Trial to Evaluate Ganovo（Danoprevir ） Combined With Ritonavir in the Treatment of SARS-CoV-2 Infection

Conditions
-----------------
COVID-19

Intervention / Treatment
-----------------
* Drug: Ganovo+ritonavir+/-Interferon nebulization


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Aged 18-75 years old; Pneumonia patients with new coronavirus infection were confirmed to be positive by RT-PCR and clinical manifestations. The diagnosis standard refers to the diagnosis and treatment plan for pneumonia with new coronavirus infection (Current Trial Version); Patients with newly diagnosed respiratory system discomfort who have been hospitalized (the diagnosis time of respiratory system discomfort shall not exceed 7 days); Women and their partners who have no planned pregnancy for nearly half a year and are willing to take effective contraceptive measures within 30 days from the first administration of the study drug to the last administration; Agree not to participate in other clinical research within 30 days from the first administration of the study drug to the last administration; Patients who voluntarily sign informed consent. Exclusion Criteria: The pneumonia patients with severe new coronavirus infection met one of the following conditions: respiratory distress, RR >= 30 times / min; or SaO2 / SpO2 <93% in resting state; or arterial partial pressure of oxygen (PaO2) / concentration of oxygen (FiO2) <300MMHG (1mmhg = 0.133kpa); Pneumonia patients with severe new coronavirus infection meet one of the following conditions: respiratory failure and need mechanical ventilation; or shock; or other organ failure combined with ICU monitoring treatment; Severe liver disease (such as child Pugh score >=C, AST > 5 times upper limit); Patients with contraindications specified in the instructions of ritonavir tablets; The pregnancy test of female subjects in the screening period was positive; The researchers judged that it was not suitable to participate in this clinical trial (for example, patients who may be transferred to another hospital during the study period; patients with multiple basic diseases, etc.).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ganovo+ritonavir with or without interferon nebulization<br> | Drug: Ganovo+ritonavir+/-Interferon nebulization<br>* Ganovo one tablet (100mg / tablet) at a time, twice a day, up to 14 days. Ritonavir one tablet(100mg / tablet) at a time, twice a day, up to 14 days.With or without spray inhalation of interferon, 50μg / time for adults, twice a day up to 14 days.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of composite adverse outcomes | Defined as SPO2≤ 93% without oxygen supplementation, PaO2/FiO2 ≤300mmHg or a respiratory rate ≥30 breaths per min without supplemental oxygen | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to recovery | Clinical recovery was defined as sustained (48 hours) alleviation of illness based on symptom scores (fever, cough, diarrhea, myalgia, dyspnea) all being absent and no evidence for progression (newly-presented dyspnea, SpO2 decline ≥3%, respiratory rate ≥ 24 breaths per min without supplemental oxygen). | 14 days | 
| Rate of no fever | Rate of no fever | 14 days | 
| Rate of no cough | Rate of no cough | 14 days | 
| Rate of no dyspnea | Rate of no dyspnea | 14 days | 
| Rate of no requiring supplemental oxygen | Rate of no requiring supplemental oxygen | 14 days | 
| Rate of undetectable New coronavirus pathogen nucleic acid | Rate of undetectable New coronavirus pathogen nucleic acid | 14 days | 
| Rate of mechanical ventilation | Rate of mechanical ventilation | 14 days | 
| Rate of ICU admission | Rate of ICU admission | 14 days | 
| Rate of serious adverse event | Rate of serious adverse event | 14 days |