Efficacy Evaluation of Shen Cao Gan Jiang Tang on Mild and Moderate COVID-19 Patients

Efficacy of Shen Cao Gan Jiang Tang (Gan Cao Gan Jiang Tang With Ginseng) on Mild and Moderate COVID-19 Patients: A Multicenter, Prospective, Randomized Controlled Trial

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus that causes COVID-19 (coronavirus disease 2019). Patients with COVID-19 may experience various clinical manifestations, from no symptoms to critical illness such as severe pneumonia and acute respiratory distress syndrome (ADRS). So far, there is no specific medication for COVID-19; hence, the current available treatments mostly aim at symptoms management and supportive care. From traditional medicine perspective, COVID-19 is classified as warm-disease (Wen-yi). The main points of treatment for COVID-19 in early stage based on traditional medicine perspective are strengthen the Protective Qi (Wei Qi - the body immune system), and restore the balance of Qi, which is vital biological energy to prevent the invasion of external pathogens, including the SARS-CoV-2 virus. The Shen Cao Gan Jiang Tang have including Gan Cao Gan Jiang Tang (GGT) with the addition of Ginseng. This formula is originated from Shang Han Lun (Treatise on Febrile Diseases Caused by Cold) by Zhang Zhong-jing, used to enhance the Protective Qi, treat the early stage of Febrile Diseases, This clinical trial aims to evaluate the efficacy of the Shen Cao Gan Jiang Tang on mild and moderate COVID-19 patients

Study Overview

• Status: Completed
• Conditions: COVID-19 Respiratory Infection; Herbal Medicine
• Intervention / Treatment: Drug: Shen Cao Gan Jiang Tang (Gan Cao Gan Jiang Tang with Ginseng)

Detailed Description

The main objectives of this clinical trial:

1. Assess the efficacy of Shen Cao Gan Jiang Tang (Gan Cao Gan Jiang Tang with Ginseng) in addition to the standard of care on reducing duration and severity of symptoms compared with the standard of care in mild and moderate COVID-19 patients.
2. Assess the efficacy of Shen Cao Gan Jiang Tang (Gan Cao Gan Jiang Tang with Ginseng) in addition to the standard of care on reducing the proportion of patients progressed to severe level compared with the standard of care in mild and moderate COVID-19 patients.
3. Assess the efficacy of Shen Cao Gan Jiang Tang (Gan Cao Gan Jiang Tang with Ginseng) in addition to the standard of care on reducing the time required to meet discharge standards compared with the standard of care in mild and moderate COVID-19 patients.

This study is investigated by the following hypotheses: combining Shen Cao Gan Jiang Tang (Gan Cao Gan Jiang Tang with Ginseng) with the standard of care is effective in reducing the duration and severity of symptoms, reducing the proportion of patients progressed to severe level, and reducing the length of hospital stay on mild and moderate COVID-19 patients

• Study Type: Interventional
• Enrollment (Actual): 300
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Van-Dan Nguyen, MD; Phone Number: +84983731326; Email: nguyenvandan@ump.edu.vn

Study Locations

• Vietnam
  • Ho Chi Minh, Vietnam, 700000
    • University of Medicine and Pharmacy at Ho Chi Minh City

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• From full 18 to 64 years old;
• The patient was diagnosed with SARS-CoV-2 infection by RT-PCR confirmation (+) and CT < 30.
• Patients classified as mild (acute upper respiratory tract infection): patients infected with SARS-CoV-2 early in the first 5 days from the time of having one of the non-specific clinical symptoms such as fever, cough dry, sore throat, stuffy nose, fatigue, headache, muscle pain, decreased taste, decreased sense of smell. And there are no signs of pneumonia or hypoxia, respiratory rate ≤ 20 times/min, Saturation of Peripheral Oxygen (SpO2) ≥ 96% when breathing air.
• Patients classified as moderate (Pneumonia): patients infected with SARS-CoV-2 in the first 10 days from the time of having one of the non-specific clinical symptoms, showing signs of pneumonia (fever, cough, dyspnea, tachypnea >20 breaths/min) and no signs of severe pneumonia, Saturation of Peripheral Oxygen (SpO2) ≥ 93% when breathing air.
• Inpatient treatment
• Subjects do not use any other medicines with herbal ingredients for underlying conditions or any other purposes;
• Voluntary participation in the study by signing an informed consent
• Patients who have not been vaccinated or have just received 1 dose of COVID-19 vaccine

Exclusion Criteria:

• Severe or critical COVID-19 based on the COVID-19 severity scale of Vietnam Ministry of Health;
• Chronic obstructive pulmonary disease, kidney failure requiring dialysis or creatinine ≥ 2.0mg/dl through medical history; parenteral or parenteral nutrition, uncontrolled type 2 diabetes (HbA1c > 7%), uncontrolled hypertension (value > 160/100 mmHg), uncontrolled coronary artery disease (new/currently established) requires medication adjustment), heart failure, neurological disease (eg, acute stroke, polyneuritis within 1 month) or mental illness, active tuberculosis, active autoimmune disease;
• Have a chronically weakened immune system (AIDS, cancer, undergoing chemotherapy-radiotherapy in the past six months, immunosuppressive disease);
• Taking immunosuppressive drugs (e.g., anti-rejection treatment after organ transplant or blood stem cell transplant);
• Allergic to products that contain ginseng;
• Pregnant or lactating women;
• Already participating in another clinical trial;
• The patient has received 2 doses of COVID-19 vaccine.

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: • Experimental: Investigational arm; Patients take Shen Cao Gan Jiang Tang (Gan Cao Gan Jiang Tang with Ginseng) and the Standard of Care (SOC) for the treatment of COVID-19 based on the Vietnam Ministry of Health guideline.	Drug: Shen Cao Gan Jiang Tang (Gan Cao Gan Jiang Tang with Ginseng); Patients take Shen Cao Gan Jiang Tang (Gan Cao Gan Jiang Tang with Ginseng), one bag of decoction (90ml) two times a day for 10 days. In additional, patients also receive the Standard of Care (SOC) for the treatment of COVID-19 based on the Vietnam Ministry of Health guideline. Ingredients per formula (tang): 12 grams of honey-fried Radix Glycyrrhizae, 6 grams of Rhizoma Zingiberis (stir-baked), 6 grams of Panax Ginseng. The decoction of concentrated extract is packed into aluminum foil vacuum bag, 90ml per bag, 1 formula (tang) is equivalent to 2 bags. Patients use the decoction directly from the bag. Daily dose: 1 bag per time, 2 times per day; Other Names: "Sâm Thảo Can khương thang (Cam thảo Can khương gia Nhân sâm)"
No Intervention: • Controlled arm; Patients receive the Standard of Care (SOC) for the treatment of COVID-19 based on the Vietnam Ministry of Health guideline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of symptoms of COVID-19	Time (days) from randomization to symptoms disappear	From Day 1 to Day 21 after randomization
The severity of the COVID-19 total and individual symptoms	Time (days) from randomization to the relief of total and individual COVID-19 symptoms scores	From Day 1 to Day 21 after randomization
Rate of progression to disease severity	Number of patients (%) progressed to severe level of COVID-19 severity scale based on the Vietnam Ministry of Health severity scale during the period of the treatment	During inpatient treatment, maximum to Day 21 after randomization
The time required to meet discharge standards	Time (days) from randomization to get required for a negative real-time polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 or CT > 30	During inpatient treatment, maximum to Day 21 after randomization
National Early Warning Score 2 (NEWS2)	Assessed by National Early Warning Score 2 (NEWS2)	During inpatient treatment, maximum to Day 21 after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cycle threshold (CT)	Cycle threshold (CT) values on the COVID-19 RT-PCR test	During inpatient treatment, maximum to Day 21 after randomization
Duration of SARS-CoV-2 virus infection	Time (days) from randomization to negative the COVID-19 RT-PCR test	During inpatient treatment, maximum to Day 21 after randomization
Mortality rate	The number of deaths (%) caused by COVID-19	From Day 1 to Day 21 after randomization
Number of participants clinically recovered	Number of patients (n) without symptoms of COVID-19 on date of discharge	From Day 1 after randomisation to Day for patients meet discharge criteria
Paracetamol/Ibuprofen intake	The number (n) of daily doses of paracetamol/ibuprofen consumed during inpatient	From Day 1 after randomisation to Day for patients meet discharge criteria
Safety evaluation	Number of patients (n) that have the side effects due to the decoction based on clinical monitoring	From Day 1 to Day 21 after randomization

Collaborators and Investigators

• Sponsor: University of Medicine and Pharmacy at Ho Chi Minh City
• Investigators: Principal Investigator: Van-Dan Nguyen, MD, University of Medicine and Pharmacy at Ho Chi Minh City

Study record dates

Study Major Dates

• Study Start (Actual): August 20, 2021
• Primary Completion (Actual): December 25, 2021
• Study Completion (Actual): December 25, 2021

Study Registration Dates

• First Submitted: September 21, 2021
• First Submitted That Met QC Criteria: September 23, 2021
• First Posted (Actual): September 24, 2021

Study Record Updates

• Last Update Posted (Actual): May 31, 2023
• Last Update Submitted That Met QC Criteria: May 28, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Respiratory Tract Infections
• Other Study ID Numbers: 458/HĐĐĐ-ĐHYD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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