Efficacy and Safety of High-dose Vitamin C Combined With Chinese Medicine Against Coronavirus Pneumonia (COVID-19)

NCT ID: NCT04664010

Last Updated: 2023-09-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-06
• Study Completion Date: 2023-09-14

Brief Summary

In December 2019, coronavirus pneumonia (COVID-19) was detected in many cases in Wuhan, China. With the rapid spread of the coronavirus, cases of COVID-19 were also reported in other cities of China and other countries. COVID-19 can cause amplification of the pulmonary inflammatory responses, including the production of a large amount of free radicals and the release of inflammatory factors, in a short time after infection, leading to lung tissue damage and dysfunction, even resulting in life-threatening respiratory distress syndrome and respiratory failure. At present, there are no effective drugs targeting COVID-19. Previous studies have shown that Buzhong Yiqi Decoction has anti-bacterial, anti-viral, and anti-allergy effects. High-dose vitamin C also has anti-oxidative and anti-toxin effects, possibly exhibiting good effects in the treatment of viral infection and critical respiratory diseases. The study objectives include (1) investigate whether Buzhong Yiqi Decoction can improve the clinical symptoms of patients with mild and severe COVID-19 and accelerate recovery and to further investigate the clinical efficacy of high-dose vitamin C combined with traditional Chinese medicine in the treatment of mild and severe COVID-19; (2) to assess the safety of high-dose vitamin C combined with Chinese medicine in the treatment of mild and severe COVID-19.

Detailed Description

Preparation prior to treatment

1. Record of age, sex, race, height, body mass, body mass index, body temperature, blood pressure, pulse, and respiratory rate;

2. Record of previous medical history, current medical history, treatment history, concomitant disease/treatment history;

3. Record of laboratory tests: routine blood test, routine stool and urine tests, fecal occult blood test, C-reactive protein measurement, biochemical assay, PCR testing for respiratory virus, tumor marker test, and ABO typing

4. Cytokine detection: Serum levels of interleukin-6, interleukin-10, and tumor necrosis factor-alpha (TNF-α)

5. Auxiliary examination: Chest CT for assessment of lung infection

Chinese medicine treatments Chinese medicine treatments include oral administration of concentrated Chinese herbal decoction, fumigation/inhalation of Chinese medicine and vitamin C, and bolus administration of vitamin C.

Traditional Chinese and western medicine prescription details Traditional Chinese medicine treatment details Prescription 1: Buzhong Yiqi plus and minus formula (recommended for patients who had no fever and those who are in the convalescent period): This formula is composed of Radix Astragali 30 g, Radix Ginseng 15 g, Radix Glycyrrhizae 15 g, Rhizoma Atractylodis Macrocephalae 10 g, Pericarpium Citri Reticulatae 6 g, Radix Angelicae Sinensis 10 g, Fructus Jujubae 6, Rhizoma Zingiberis Recens 9 pieces, Radix Bupleuri 12 g, Rhizoma Cimicifugae 6 g.

Preparation method: The aforementioned herbs are decocted with water. After removal of macromolecules, 50 g concentrate is left, and then packaged, 25 g/dose.

Suggested usage: 1 dose once, twice a day, taking with warm water.

Prescription 2: Huhuang Detoxicity Paste (recommended for patients who have no fever): This formula is composed of Rhizoma Coptidis 20 g, Radix Et Rhizoma Rhei 10 g, Rhizoma Atractylodis 10 g, Radix Asteris 10 g, Herba Houttuyniae 10 g, Herba Taraxaci 10 g, Rhizoma Polygoni Cuspidati 10 g, Radix Astragali 20 g.

Preparation method: The aforementioned herbs are boiled with water. The extract was subjected to high-speed centrifugation. After removal of impurities, 50 g concentrate is left, and then packaged, 25 g/dose.

Suggested usage: One dose once, twice a day, taking with warm water.

Prescription 3: Baimu Qingre Jiedu Paste This formula is composed of Radix Puerariae 15 g, Radix Angelicae Dahuricae 12 g, Flos Magnoliae 9 g, Radix Isatidis 30 g, Fructus Forsythiae 15 g, Bulbus Fritillariae Thunbergii 12 g Preparation method: The aforementioned herbs are boiled with water. The extract was subjected to high-speed centrifugation. After removal of impurities, 50 g concentrate is left, and then packaged, 25 g/dose.

Suggested usage: One dose once, twice a day, taking with warm water.

Prescription 4: Fumigation/inhalation of Chinese herbs and vitamin C The formula consists of Rhizoma Coptidis 20 g, Radix Et Rhizoma Rhei 10 g, Rhizoma Atractylodis Macrocephalae 10 g, Radix Astragali 10 g, Radix Asteris 10 g, Herba Houttuyniae 10 g, Herba Taraxaci 10 g, Rhizoma Polygoni Cuspidati 10 g, Radix Astragali 20 g.

Preparation method: The aforementioned herbs are boiled with water. The extract was subjected to high-speed centrifugation. After removal of impurities, 50 g concentrate is left, and then packaged, 25 g/dose.

Fumigation/inhalation method: 3L of water is added to the intelligent rice cooker (specification 5L), and then the aforementioned semifluid paste is also placed in the cooker. After boiling, 10 g vitamin C is added. The oxygen tube is inserted into the bottom of the traditional Chinese medicine solution (oxygen flow is about 3-4 L/min). The steam is sucked with the mouth and nose alternately, 30-40 minutes once, 3-7 times a day. Patients take vitamin E capsule and folic acid every day.

Bolus administration of vitamin C 100 mL of 5% glucose containing vitamin C (10 g/60 kg body mass) is intravenously administered twice a day.

Western medicine treatment details Atomized inhalation of 5 million U α-interferon and 2 mL sterilized water, twice a day; 0.2 g arbidol, three times a day, treatment course no more than 10 days; intravenous administration of ribavirin 500 mg, once every 12 hours, treatment course no more than 10 days; intravenous administration of 10 g immunoglobulin C, once a day, 3-5 days. Anti-bacterial infection treatment is given to the patients who have yellow sputum and increased levels of procalcitonin and other bacterial infection specific indicators.

Notes for case and course record The medical record of integrated Chinese and western medicine treatment for each case should be carefully filled. A summary of the medical record is made every three days. The name and dosage of the traditional Chinese medicine and western medicine used, the route of administration, curative effect, and side effects are recorded. The record form of the curative effect should be filled every day.

Conditions

COVID-19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

moderate COVID-19 group

patients with moderate COVID-19 receiving western medicine treatment

Group Type: EXPERIMENTAL

Alpha-interferon alpha, abidol, ribavirin, Buzhong Yiqi plus and minus formula, Huhuang Detoxicity Paste, Baimu Qingre Jiedu Paste, fumigation/inhalation of vitamin C

Intervention Type: DRUG

Atomized inhalation of 5 million U α-interferon and 2 mL sterilized water, twice a day; 0.2 g arbidol, three times a day, treatment course no more than 10 days; intravenous administration of ribavirin 500 mg, once every 12 hours, treatment course no more than 10 days; intravenous administration of 10 g immunoglobulin C, once a day, 3-5 days. Anti-bacterial infection treatment is given to the patients who have yellow sputum and increased levels of procalcitonin and other bacterial infection specific indicators.

severe COVID-19 group

patients with severe COVID-19 receiving western medicine treatment

Group Type: EXPERIMENTAL

Alpha-interferon alpha, abidol, ribavirin, Buzhong Yiqi plus and minus formula, Huhuang Detoxicity Paste, Baimu Qingre Jiedu Paste, fumigation/inhalation of vitamin C

Intervention Type: DRUG

Atomized inhalation of 5 million U α-interferon and 2 mL sterilized water, twice a day; 0.2 g arbidol, three times a day, treatment course no more than 10 days; intravenous administration of ribavirin 500 mg, once every 12 hours, treatment course no more than 10 days; intravenous administration of 10 g immunoglobulin C, once a day, 3-5 days. Anti-bacterial infection treatment is given to the patients who have yellow sputum and increased levels of procalcitonin and other bacterial infection specific indicators.

moderate COVID-19 with traditional Chinese medicine group

patients with moderate COVID-19 receiving western medicine treatment + traditional Chinese medicine + intravenous administration of 5% glucose

Group Type: EXPERIMENTAL

Alpha-interferon, abidol, ribavirin, Buzhong Yiqi plus and minus formula, Huhuang Detoxicity Paste, Baimu Qingre Jiedu Paste and 5% glucose

Intervention Type: DRUG

Buzhong Yiqi plus and minus formula: 1 dose once, twice a day, taking with warm water. Huhuang Detoxicity Paste: One dose once, twice a day, taking with warm water; Baimu Qingre Jiedu Paste: One dose once, twice a day, taking with warm water; Fumigation/inhalation of Chinese herbs and vitamin C: 30-40 minutes once, 3-7 times a day. Patients take vitamin E capsule and folic acid every day. plus invention 1

moderate COVID-19 with combination therapy group

patients with moderate COVID-19 receiving western medicine treatment + traditional Chinese medicine + intravenous administration of 5% glucose containing high-dose vitamin C

Group Type: EXPERIMENTAL

Alpha-interferon, abidol, ribavirin, Buzhong Yiqi plus and minus formula, Huhuang Detoxicity Paste, Baimu Qingre Jiedu Paste and 5% glucose

Intervention Type: DRUG

Buzhong Yiqi plus and minus formula: 1 dose once, twice a day, taking with warm water. Huhuang Detoxicity Paste: One dose once, twice a day, taking with warm water; Baimu Qingre Jiedu Paste: One dose once, twice a day, taking with warm water; Fumigation/inhalation of Chinese herbs and vitamin C: 30-40 minutes once, 3-7 times a day. Patients take vitamin E capsule and folic acid every day. plus invention 1

severe COVID-19 with traditional Chinese medicine group

patients with severe COVID-19 receiving western medicine treatment + traditional Chinese medicine + intravenous administration of 5% glucose

Group Type: EXPERIMENTAL

Alpha-interferon, abidol, ribavirin, Buzhong Yiqi plus and minus formula, Huhuang Detoxicity Paste, Baimu Qingre Jiedu Paste and high-dose vitamin C treatment

Intervention Type: DRUG

invention 1 plus invention 2 plus 100 mL of 5% glucose containing vitamin C (10 g/60 kg body mass) is intravenously administered twice a day.

severe COVID-19 with combination therapy group

patients with severe COVID-19 receiving western medicine treatment + traditional Chinese medicine + intravenous administration of 5% glucose containing high-dose vitamin C

Group Type: EXPERIMENTAL

Alpha-interferon, abidol, ribavirin, Buzhong Yiqi plus and minus formula, Huhuang Detoxicity Paste, Baimu Qingre Jiedu Paste and high-dose vitamin C treatment

Intervention Type: DRUG

invention 1 plus invention 2 plus 100 mL of 5% glucose containing vitamin C (10 g/60 kg body mass) is intravenously administered twice a day.

Interventions

Alpha-interferon alpha, abidol, ribavirin, Buzhong Yiqi plus and minus formula, Huhuang Detoxicity Paste, Baimu Qingre Jiedu Paste, fumigation/inhalation of vitamin C

Atomized inhalation of 5 million U α-interferon and 2 mL sterilized water, twice a day; 0.2 g arbidol, three times a day, treatment course no more than 10 days; intravenous administration of ribavirin 500 mg, once every 12 hours, treatment course no more than 10 days; intravenous administration of 10 g immunoglobulin C, once a day, 3-5 days. Anti-bacterial infection treatment is given to the patients who have yellow sputum and increased levels of procalcitonin and other bacterial infection specific indicators.

Intervention Type: DRUG

Alpha-interferon, abidol, ribavirin, Buzhong Yiqi plus and minus formula, Huhuang Detoxicity Paste, Baimu Qingre Jiedu Paste and 5% glucose

Buzhong Yiqi plus and minus formula: 1 dose once, twice a day, taking with warm water. Huhuang Detoxicity Paste: One dose once, twice a day, taking with warm water; Baimu Qingre Jiedu Paste: One dose once, twice a day, taking with warm water; Fumigation/inhalation of Chinese herbs and vitamin C: 30-40 minutes once, 3-7 times a day. Patients take vitamin E capsule and folic acid every day. plus invention 1

Intervention Type: DRUG

Alpha-interferon, abidol, ribavirin, Buzhong Yiqi plus and minus formula, Huhuang Detoxicity Paste, Baimu Qingre Jiedu Paste and high-dose vitamin C treatment

invention 1 plus invention 2 plus 100 mL of 5% glucose containing vitamin C (10 g/60 kg body mass) is intravenously administered twice a day.

Intervention Type: DRUG

Other Intervention Names

Western medicine treatment; Traditional Chinese medicine treatment plus Western medicine treatment; Traditional Chinese medicine treatment plus Western medicine treatment plus Bolus administration of vitamin C

Eligibility Criteria

Inclusion Criteria

1. Patients with mild and severe COVID-19 confirmed according to the Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 7) that was issued by the National Health Commission & State Administration of Traditional Chinese Medicine;

2. Patients with suspected COVID-19 who meet one of the following pathogenic or serological evidence are also confirmed infected with the virus: a) COVID-19 nucleic acid test positive, as confirmed by real-time fluorescence RT-PCR detection; b) viral gene sequencing is highly homologous with the known COVID-19; c) serum test positive for both COVID-19 specific IgM and IgG antibodies; d) serum IgG antibody turns positive from negative or IgG antibody level in the recovering phase rises four times or higher than in the acute phase

3. Patients with moderate COVID-19 have fever and respiratory symptoms and present with the imaging features of coronavirus disease

4. Subjects will be considered developing severe COVID-19 if one of the following conditions occur: a) dyspnea, respiratory ≥ 30 beats/minute, blood oxygen saturation ≤ 93%, partial pressure of arterial oxygen (PaO2)/ fraction of inspired oxygen ratio (FiO2) ≤ 300, and /or lung infiltrates > 50% within 24 to 48 hours

5. Age > 18 years, of either sex Provision of written informed consent

Exclusion Criteria

1. Patients with critical COVID-19 presenting with shock, acute respiratory distress syndrome, multiple organ failure

2. Patients with mild COVID-19

3. Pregnant or lactating woman

4. Upon the investigator's judgment, patients had the diseases that possibly influence patient participation in this study or study outcomes (such as malignant disease, autoimmune disease, severe malnutrition, liver and kidney disease, blood disease, nervous system disease, endocrine diseases) or currently suffer from the diseases that seriously affect the immune system (such as human immunodeficiency virus infection) or blood system, or splenectomy/organ transplantation.

5. Upon the request of the investigators or sponsors, patients with other acute malignant or chronic disease or mental disorder are not suitable for participation in this study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Xi'an International Medical Center Hospital

OTHER

Sponsor Role: lead

Responsible Party

Qiang Yin

President

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Xijing He, MD

Role: STUDY_CHAIR

Xi'an International Medical Center Hospital

Yongping Liu

Role: PRINCIPAL_INVESTIGATOR

Xi'an International Medical Center Hospital

Xudong Yang

Role: PRINCIPAL_INVESTIGATOR

Xi'an International Medical Center Hospital

Yali Wang

Role: PRINCIPAL_INVESTIGATOR

Xi'an International Medical Center Hospital

Yifan Feng

Role: PRINCIPAL_INVESTIGATOR

Xi'an International Medical Center Hospital

Kuiwei Zhang

Role: PRINCIPAL_INVESTIGATOR

Xi'an International Medical Center Hospital

Jiayue Shan

Role: PRINCIPAL_INVESTIGATOR

Xi'an International Medical Center Hospital

Lei Shang

Role: PRINCIPAL_INVESTIGATOR

Xi'an International Medical Center Hospital

Zhijian Cheng

Role: PRINCIPAL_INVESTIGATOR

Second Affiliated Hospital of Xi'an Jiaotong University

Rui Wang

Role: PRINCIPAL_INVESTIGATOR

Second Affiliated Hospital of Xi'an Jiaotong University

Guoyu Wang

Role: PRINCIPAL_INVESTIGATOR

Second Affiliated Hospital of Xi'an Jiaotong University

Hui Gao

Role: PRINCIPAL_INVESTIGATOR

Xi'an International Medical Center Hospital

Shanjiao Jiang

Role: PRINCIPAL_INVESTIGATOR

Xi'an International Medical Center Hospital

Shenhao Liu

Role: PRINCIPAL_INVESTIGATOR

Xi'an International Medical Center Hospital

Locations

Xi'an International Medical Center Hospital

Xi'an, Shaanxi, China

Countries

China

Other Identifiers

XianInternationalMCH_HXJ

Identifier Type: -

Identifier Source: org_study_id