A Chinese herbal medicine preparation (Pei Tu Qing Xin) for children with moderate-to-severe atopic eczema: a pilot randomized controlled trial

Dear Editor, Atopic eczema (AE), also termed atopic dermatitis, is a chronic and relapsing inflammatory skin disease. The prevalence and burden of AE are increasing globally. Systemic immunomodulating medications including corticosteroids and immunosuppressive drugs are efficacious agents for difficult‐to‐treat or refractory moderate or severe AE, but they are not used routinely due to safety concerns.1 Some patients with AE have reported using complementary and alternative medicines including Chinese herbal medicine (CHM). A Cochrane systematic review of 28 studies involving 2306 participants with AE found that an oral CHM formula could improve quality of life in children with AE.2 However, the current state of evidence is limited to support routine use of CHM for AE. Further rigorous randomized controlled trials (RCTs) are needed to determine whether CHM is beneficial. A double‐blind, randomized, placebo‐controlled pilot trial of the nine‐herb CHM preparation Pei Tu Qing Xin granules (PTQX) involving 30 children with moderate‐to‐severe AE was undertaken between August 2016 and September 2017 in Guangzhou, China. PTQX was composed of baizhu (Atractylodes macrocephala), taizishen (Pseudostellaria heterophylla), shanyao (Dioscorea opposita), yiyiren (Coix lacryma‐jobi), baimiaogen (Imperata cylindrica), lianqiao (Forsythia suspensa), gancao (Glycyrrhiza glabra), baixianpi (Dictamnus dasycarpus) and zhenzhufen [Pteria martensii (Dunker)]. PTQX is currently used at the dermatology department of the Guangdong Provincial Hospital of Chinese Medicine (GPHCM) based on expert consensus.3 An in vivo study reported that PTQX reduced histamine‐induced itch in guinea pigs, and 4‐aminopyridine‐ or dextran‐induced itch in mice.4 This pilot RCT aimed to determine protocol feasibility and compliance, to gather preliminary data and to monitor safety. Findings from this pilot RCT will inform planning of a full‐scale RCT. After we had obtained written informed consent forms signed by the parents or guardians, participants were randomized to receive either oral PTQX or identical‐appearing placebo twice daily for 12 weeks, with follow‐up assessment conducted at 16 weeks (4 weeks after the treatment phase). The primary outcome was change in Eczema Area and Severity Index (EASI),5 with the secondary outcomes being change in Patient‐Oriented Eczema Measure (POEM),6 the Children's Dermatology Life Quality Index (CDLQI),7 use of concomitant medications and adverse events. The trial protocol was approved by the GPHCM ethics committee and the Royal Melbourne Institute of Technology University Human Research Ethics Committee. The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12614001172695) prior to recruitment of participants. Block randomization codes were generated by SAS 9·2 software (SAS Institute Inc., Cary, NC, U.S.A.) and allocated to the participants with a central allocation system developed by the Department of Research Methodology of GPHCM. Neither the trial participants nor the investigators knew the participant allocation to the treatment or placebo groups. Data were analysed using SPSS version 22 (IBM, Armonk, NY, U.S.A.). Intention‐to‐treat analysis was performed using the data imputation method of last observation carried forward. All comparisons were two tailed, with P‐values < 0·05 considered statistically significant. The full clinical trial design including the inclusion and exclusion criteria and trial medication details can be found in the published study protocol.8 Screened from 121 potential eligible participants, nine boys and 21 girls aged 6–16 years were recruited from the dermatology outpatient department of GPHCM (16 in the PTQX group). The participants in both groups were highly compliant with the protocol in terms of taking the trial medications and completing all case record forms. The withdrawal or dropout rate was within an acceptable 10% rate (one withdrawal and one dropout in the PTQX group; one dropout in the placebo group). The characteristics of the two groups were balanced at baseline and are summarized in Table 1. There were no between‐group differences in score changes for EASI, POEM or CDLQI at the end of treatment (week 12). While not statistically significant, the mean scores of EASI, POEM and CDLQI in the PTQX group were lower than those in the placebo group at the end of the follow‐up period (week 16) (Table 1). Primary and secondary outcomes: comparisons within groups and between groups Data are the mean ± SD. The end of treatment was at week 12, and the end of follow‐up at week 16. n = 30 for all groups. CDLQI, Children's Dermatology Life Quality Index; CI, confidence interval; EASI, Eczema Area and Severity Index; POEM, Patient‐Oriented Eczema Measure; PTQX, Pei Tu Qing Xin granules. Primary and secondary outcomes: comparisons within groups and between groups Data are the mean ± SD. The end of treatment was at week 12, and the end of follow‐up at week 16. n = 30 for all groups. CDLQI, Children's Dermatology Life Quality Index; CI, confidence interval; EASI, Eczema Area and Severity Index; POEM, Patient‐Oriented Eczema Measure; PTQX, Pei Tu Qing Xin granules. During the trial, 21 children (10 in the PTQX group) used topical corticosteroid creams (TCS) as concomitant medication. While differences in the volume of use of TCS were not statistically significant between the two groups, there was lower TCS use in the PTQX group at the end of the trial (week 16). There were three (one in the PTQX group) mild adverse events (skin rashes or vomiting) and no severe adverse events during the trial period. No hepatic or renal function abnormalities were found in any participant during the treatment period. The findings from this pilot RCT are limited; nevertheless, these findings can be used to calculate the sample size for the full‐scale RCT. The study revealed that the adverse events were mild and the protocol is implementable, hence an appropriately powered RCT is warranted. Funding sources: this project was supported by the Australian Government Research Training Program Scholarship and research funding through the China–Australia International Research Centre for Chinese Medicine, a joint initiative of the Royal Melbourne Institute of Technology (RMIT) University, Australia, and Guangdong Provincial Hospital of Chinese Medicine (GPHCM), China. The project was also funded by the Traditional Chinese Medicine Bureau, Guangdong Provincial Government, China, grant number [2014] 539. Conflicts of interest: D.C. developed the Chinese herbal medicine formula PTQX, which has been patented. All of the other authors declare no competing interests.