Huashi Baidu Granule in the Treatment of Pediatric Patients With Mild Coronavirus Disease 2019
Condition: Coronavirus Disease 2019
MeSH terms: Coronavirus Infections; COVID-19
Study type: Interventional

Summary: 
      The investigators conducted a single-center, open-label, parallel-group randomized controlled
      trial to assess the efficacy and safety of a Chinese herb compound granule Huashi Baidu
      granule (HSBDG) in pediatric patients with laboratory-confirmed mild COVID-19. 108 recruited
      children (aged 3 to 18 years) with laboratory-confirmed mild COVID-19 were randomly allocated
      2:1 to receive oral HSBDG for 5 consecutive days (intervention group) and to receive compound
      pholcodine oral solution for 5 consecutive days (control group). The negative conversion time
      of SARS-CoV-2 nucleic acid and symptom scores were recorded.
    

Detailed description: 
      This was a single-center, open-label, parallel-group randomized controlled clinical trial,
      with an allocation ratio of 2:1. Written consent was obtained from the parents of all
      participants. The study was conducted in accordance with the Declaration of Helsinki and the
      current Good Clinical Practice. The protocol was approved by the Institutional Ethics
      Committee of Shanghai Children's Medical Center (SCMCIRB-K2022046-1) Participants and setting
      Children who attended the COVID-19 Fangcang Shelter Hospitals in Shanghai, China, with
      laboratory-confirmed mild COVID-19 were screened for eligibility. The inclusion criteria were
      as follows: 1) compliance with the diagnostic criteria for mild COVID-19; 2) age 3 to 18
      years. Participants who had underlying disease(s) such as chronic pulmonary disease,
      immunodeficiency, tumors, etc., allergy or intolerance to taking Chinese medicine herbs or
      compound pholcodine oral solution, or poor compliance (defined as inability to comply with
      the protocol) were excluded.

      Sample size Two-sample T-tests allowing unequal variance were used for sample size
      calculation by Power Analysis and Sample Size Software 2021 (NCSS, LLC. Kaysville, Utah,
      USA). Group sample sizes of 64 and 32 achieve 85.0% power to reject the null hypothesis of
      equal means when the population mean difference is μ1 - μ2 = 10 - 11 = -1 with standard
      deviations of 1.42 for the intervention group and 1.56 for the control group, and with a
      significance level (alpha) of 0.05 using a two-sided two-sample unequal-variance t-test. The
      aim was to recruit 108 participants to allow for a 12% attrition rate.

      Randomization and Blinding Patients were randomly assigned 2:1 to the intervention group or
      the control group by a researcher who was not otherwise involved in the study using random
      sequences generated by SPSS software 25.0 (IBM SPSS Statistics, Armonk, NY, USA). This was an
      open-label trial. Patients, investigators, and statisticians were not masked to the group
      assignment.

      Intervention In the intervention group, patients were given HSBDG the day after
      randomization, with a dose of 2.5g for age 3 to 6 years, 5 g for age 7 to 12 years, and 10 g
      for age 13 to 18 years, twice daily for 5 consecutive days. In the control group, patients
      were given compound pholcodine oral solution (Bright Future Pharmaceuticals Factory, Hong
      Kong, CHN) the day after randomization, with a dose of 5 ml for age 3 to 6 years and 10 ml
      for age 7 to 18 years, three times daily for 5 consecutive days. The day of randomization was
      set as day 0. By free Instant messaging software (WeChat; Tencent, Shenzhen, CHN) available
      on smart phones, parents received questionnaires (Table S1 for symptom scores at days 0, 3
      and 5) and be asked to complete them truthfully. For each patient, one SARS-CoV-2 nucleic
      acid real-time PCR test for the specimen from the upper respiratory tract was performed
      daily. Patients would be not considered to be discharged until two consecutive negative
      reports were confirmed.

      Primary outcome The primary outcome of the study was the time for SARS-CoV-2 nucleic acid
      negative conversion after randomization. The time from day 0 to the day of two consecutive
      negative reports confirmed was defined as the negative conversion time.

      Secondary outcomes The secondary outcomes for the study were symptom improvements at days 3
      and 5, and antibiotic use and side effects from day 1 to discharge. Total symptom score was
      the sum of the scores of primary symptoms (fever, cough, expectoration, sore throat,
      wheezing, and chest pain) and secondary symptoms (dry stool, dark urine or oliguria, poor
      appetite, low energy, tired, nausea or vomiting, and diarrhea).

      Statistical analysis Data were presented as frequencies and percentages for categorical
      variables and as medians and interquartile range (IQR) for continuous variables. Categorical
      variables were compared by the chi-square test. Continuous variable comparisons were
      performed by the Mann-Whitney U test. P-value < 0.05 was considered to be statistical
      significance. All analyses were performed using SPSS software 25.0 (IBM SPSS Statistics,
      Armonk, NY, USA).
    

Intervention name(s): Huashi Baidu granule; compound pholcodine oral solution
Intervention type(s): Drug; Drug
Intervention description(s): Patients were given HSBDG the day after randomization, with a dose of 2.5g for age 3 to 6 years, 5 g for age 7 to 12 years, and 10 g for age 13 to 18 years, twice daily for 5 consecutive days.; Patients were given compound pholcodine oral solution (Bright Future Pharmaceuticals Factory, Hong Kong, CHN) the day after randomization, with a dose of 5 ml for age 3 to 6 years and 10 ml for age 7 to 18 years, three times daily for 5 consecutive days.
Intervention MeSH terms: Pholcodine
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: randomly allocated 2:1 to receive oral HSBDG for 5 consecutive days (intervention group) and to receive compound pholcodine oral solution for 5 consecutive days (control group)
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: COVID-19; SARS-CoV-2; Omicron; Traditional Chinese Medicine; Clinical trial