Clinical trial NCT04664010: Efficacy and Safety of High-dose Vitamin C Combined With Chinese Medicine Against Coronavirus Pneumonia (COVID-19)
Official title: Efficacy and Safety of High-dose Vitamin C Combined With Traditional Chinese Medicine in the Treatment of Moderate and Severe Coronavirus Pneumonia (COVID-19)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: COVID-19
Keywords: COVID-19
vitamin C
traditional Chinese medicine
Lead sponsor: Xi'an International Medical Center Hospital
Sponsor class: OTHER
First posted: 2020-12-11
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: participants are assigned to one of two or more groups in parallel for the duration of the study
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Recovery time
timeFrame: From date of randomization until the date of discharge, assessed up to 6 months
Secondary outcomes:
measure: Time of disappearance of fever symptoms
timeFrame: From date of randomization until the date of discharge, assessed up to 6 months
measure: The rate of conversion from COVID-19 positive to COVID-19 negative
timeFrame: From date of randomization until the date of discharge, assessed up to 6 months.
measure: Time of disappearance of cough
timeFrame: From date of randomization until the date of discharge, assessed up to 6 months
measure: Respiratory rate
timeFrame: 1-14 days after treatment
measure: Blood oxygen saturation
timeFrame: 1-14 days after treatment
measure: PaO2
timeFrame: 1-14 days after treatment
measure: PaCO2
timeFrame: 1-14 days after treatment
measure: The time of obvious improvement as shown on chest CT scans relative to admission
timeFrame: From date of randomization until the date of discharge, assessed up to 6 months
measure: The rate of obvious improvement as shown on chest CT scans relative to admission
timeFrame: From date of randomization until the date of discharge, assessed up to 6 months
measure: Levels of C-reactive protein
timeFrame: 1-14 days after treatment
measure: Erythrocyte sedimentation rate
timeFrame: 1-14 days after treatment
measure: Levels of Procalcitonin
timeFrame: 1-14 days after treatment
measure: Levels of interleukin-6
timeFrame: 1-14 days after treatment
measure: Levels of interleukin-10
timeFrame: 1-14 days after treatment
measure: Levels of tumor necrosis factor-alpha
timeFrame: 1-14 days after treatment
Other outcomes:
measure: Ultrasound examination of the urinary system
timeFrame: 1-14 days after treatment
Locations:
city: Xi'an
country: China
facility: Xi'an International Medical Center Hospital
state: Shaanxi
Study officials:
affiliation: Xi'an International Medical Center Hospital
name: Xijing He, MD
role: STUDY_CHAIR
affiliation: Xi'an International Medical Center Hospital
name: Yongping Liu
role: PRINCIPAL_INVESTIGATOR
affiliation: Xi'an International Medical Center Hospital
name: Xudong Yang
role: PRINCIPAL_INVESTIGATOR
affiliation: Xi'an International Medical Center Hospital
name: Yali Wang
role: PRINCIPAL_INVESTIGATOR
affiliation: Xi'an International Medical Center Hospital
name: Yifan Feng
role: PRINCIPAL_INVESTIGATOR
affiliation: Xi'an International Medical Center Hospital
name: Kuiwei Zhang
role: PRINCIPAL_INVESTIGATOR
affiliation: Xi'an International Medical Center Hospital
name: Jiayue Shan
role: PRINCIPAL_INVESTIGATOR
affiliation: Xi'an International Medical Center Hospital
name: Lei Shang
role: PRINCIPAL_INVESTIGATOR
affiliation: Second Affiliated Hospital of Xi'an Jiaotong University
name: Zhijian Cheng
role: PRINCIPAL_INVESTIGATOR
affiliation: Second Affiliated Hospital of Xi'an Jiaotong University
name: Rui Wang
role: PRINCIPAL_INVESTIGATOR
affiliation: Second Affiliated Hospital of Xi'an Jiaotong University
name: Guoyu Wang
role: PRINCIPAL_INVESTIGATOR
affiliation: Xi'an International Medical Center Hospital
name: Hui Gao
role: PRINCIPAL_INVESTIGATOR
affiliation: Xi'an International Medical Center Hospital
name: Shanjiao Jiang
role: PRINCIPAL_INVESTIGATOR
affiliation: Xi'an International Medical Center Hospital
name: Shenhao Liu
role: PRINCIPAL_INVESTIGATOR
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