Clinical trial NCT04310865: Yinhu Qingwen Granula for the Treatment of Severe CoVID-19
Official title: An Adaptive, Randomized, Double-blind, Parallel-controlled Clinical Trial of Yinhu Qingwen Granula for the Treatment of Severe CoVID-19
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE2
PHASE3
Conditions: COVID-19
Severe Pneumonia
Chinese Medicine
Lead sponsor: China Academy of Chinese Medical Sciences
Sponsor class: OTHER
Collaborators: name: Wuhan Leishenshan Hospital
name: The First Affiliated Hospital of Dalian Medical University
name: Tanshan People's Hospital
name: North China University of Science and Technology Affiliated Hospital
name: Jizhong Energy Fengfeng Group Hospital
First posted: 2020-03-17
Enrollment: 116
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: In December 2019, Wuhan, in Hubei province, China, became the center of an outbreak of pneumonia caused by CoVID-19, and the number of cases of infection with CoVID-19 identified in Wuhan increased markedly over the later part of January 2020, with cases identified in multiple other Provinces of China and internationally.Given no specific antiviral therapy for CoVID-19 infection and the availability of Yinhu Qingwen Granula as a potential antiviral Chinese medicine based on vivo antiviral studies in CoVID-19, this adaptive, randomized,double-blind,controlled trial will evaluate the efficacy and safety of Yinhu Qingwen Granula in patients hospitalized with severe CoVID-19.

Detailed description: In December 2019, Wuhan, in Hubei province, China, became the center of an outbreak of pneumonia caused by CoVID-19, and the number of cases of infection with CoVID-19 identified in Wuhan increased markedly over the later part of January 2020, with cases identified in multiple other Provinces of China and internationally.The clinical spectrum of CoVID-19 infection appears to be wide,including asymptomatic infection, mild upper respiratory disease, severe viral pneumonia with respiratory failure, and even death. However,there is no specific antiviral therapy for CoVID-19 infection, which provides a window of opportunity for testing candidate antiviral therapies. Previous experiences with SARS and MERS-CoV, highlight the need of the early intervention with Chinese medicine, and so as for CoVID-19 infection. The treatment of Chinese medicine for CoVID-19 infection suggested its benefits to improve of clinical outcomes, reduce the risk of disease progression, accelerate recovery, and reduce intensive supportive care and long-term hospitalization.Yinhu Qingwen Granula was a kind of herbal granula made from "Yinhu Qingwen Decoction", which consists of 11 common non-toxic traditional Chinese medicine such as Polygonum cuspidatum, Honeysuckle, Nepeta, Ligustrum lucidum. Previous vivo antiviral studies showed its activity for the inbition of CoVID-19. This clinical trial is planned to evaluate the improvement of the changes in the ratio of PaO2 to FiO2 from the baseline for patients with severe CoVID-19 as the primary outcome, and to evaluate the effect of the symptoms relief and virus clearance as well as the clinical safety.

Eligibility criteria: Inclusion Criteria:

1. Age ≥18 years at time of signing Informed Consent Form;
2. Those who meet the diagnosis of severe new coronavirus pneumonia with laboratory confirmed infection with CoVID-19;
3. Lung involvement confirmed with chest imaging;
4. Hospitalized with a Pa02/Fi02 ratio ≤300mgHg;
5. 40%\> lymphocyte percentage ≥5%;
6. No difficulty swallowing oral medications.

Exclusion Criteria:

1. Allergies, those who are known to be allergic to research drugs or drug excipients;
2. The patient weighs less than 40 kg;
3. Patients with diarrhea;
4. Shock;
5. Patients with respiratory failure at the time of enrollment who need invasive mechanical ventilation;
6. The clinician judges that ICU admission is needed;
7. Patients who participated in other clinical trials within 1 month;
8. Known patients with impaired renal function (estimated creatinine clearance \<60 mL / min (male: Cr (ml / min) = (140-age) × body weight (kg) / 72 × blood creatinine concentration (mg / dl); female: Cr (ml / min) = (140-age) × weight (kg) / 85 × blood creatinine concentration (mg / dl));
9. During the screening or within 24 hours before screening, patients were found to have any of the following laboratory parameter abnormalities (based on the local laboratory reference range): ALT or AST level\> 5 times the upper limit of normal range (ULN) or ALT or AST level\> 3 times ULN and total bilirubin levels\> 2 times ULN;
10. Being pregnant or breastfeeding, or having a positive pregnancy test at the time of pre-dose inspection, or planning to become pregnant within 3 months after study treatment;
11. Will be transferred to another hospital which is not the study site within 72 hours.

Primary outcomes:
measure: changes in the ratio of PaO2 to FiO2 from baseline
timeFrame: Day 10
Secondary outcomes:
measure: PaO2
timeFrame: up to 30 days
measure: blood oxygen saturation (SpO2)
timeFrame: up to 30 days
measure: clinical status rating on the 7-point ordinal scale
timeFrame: up to 30 days
measure: Time to Clinical Improvement (TTCI)
timeFrame: up to 30 days
measure: Duration (hours) of non-invasive mechanical ventilation or high-flow nasal catheter oxygen inhalation use
timeFrame: up to 30 days
measure: Duration (hours) of invasive mechanical ventilation use
timeFrame: up to 30 days
measure: Duration (hours) of extracorporeal membrane oxygenation (ECMO) use
timeFrame: up to 30 days
measure: Duration (days) of Oxygen use
timeFrame: up to 30 days
measure: The proportion of the patients reporting 2019-nCoV RT-PCR negativity at Day 10 after treatment
timeFrame: Day 10
measure: The counts/percentage of Lymphocyte
timeFrame: up to 30 days
measure: Time to hospital discharge with clinical recovery from the randomisation
timeFrame: up to 30 days
measure: The incidence of critical status conversion in 30 days
timeFrame: up to 30 days
measure: All-cause mortality within 30 days
timeFrame: up to 30 days
measure: Frequency of severe adverse drug events
timeFrame: up to 30 days
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Wuhan No.7 Hospital/Jizhong Energy Fengfeng Group Hospital
state: Hubei
city: Wuhan
country: China
facility: Wuhan No.7 Hospital/North China University of Science and Technology Affiliated Hospital
state: Hubei
city: Wuhan
country: China
facility: Zhongnan Hospital of Wuhan University/Tanshan People's Hospital
state: Hubei
city: Wuhan
country: China
facility: Wuhan Leishenshan (Thunder God Mountain) Hospital/The First Affiliated Hospital of Dalian Medical University
state: Hubei
Study officials:
affiliation: Wuhan Leishenshan (Thunder God Mountain) Hospital/The First Affiliated Hospital of Dalian Medical University
name: Dong Shang, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Yangtze University Health Science Center
name: Jiang-Rong Huang, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Hubei Hospital of Traditional Chinese Medicine
name: Xiao-Dong Li, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: China Academy of Chinese Medical Sciences
name: Zhong Wang, M.D.
role: STUDY_DIRECTOR
References: