Clinical efficacy of Chinese herbal medicine formula for Graves' hyperthyroidism: A multicentre, randomized, double-blind, placebo-controlled clinical trial

Abstract

Ethnopharmacological relevance: According to the theory of traditional Chinese medicine, Graves' disease (GD) is called 'Ying Bing', which is a kind of goiter. Haizao Yuhu decoction, originated from the medical book of the Ming Dynasty 'Waikezhengzong', is a classic Chinese herbal formula for the treatment of 'Ying Bing' for more than 400 years. Pingkang granules, modified from the Chinese herbal formula Haizao Yuhu decoction specialized in GD, has shown effectiveness in several single-centre studies. However, high-quality clinical evidence for the management of GD using Pingkang granules remains insufficient.

Aim of the study: To obtain high-quality medical evidence for the treatment of GD with Pingkang granules through randomized controlled clinical trial.

Materials and methods: A multicentre, randomized, double-blinded, placebo-controlled clinical trial was designed. A total of 186 patients with Graves' hyperthyroidism from five medical centers were randomly assigned to receive methimazole [MMI] and Pingkang granules placebo (group A), MMI and Pingkang granules (group B), or MMI placebo and Pingkang granules (group C) in a 1:1:1 ratio for 12 weeks. The primary clinical outcomes were serum free triiodothyronine (FT₃) and free thyroxine (FT₄) levels from baseline until the end of the research. Secondary clinical outcomes included serum thyrotrophin receptor antibody (TRAb) levels at 4- and 12-weeks post-intervention, thyroid volume, peak systolic velocity of the superior thyroid artery (STA-PSV), 39-item version of Thyroid-Related Patient-Reported Outcome (ThyPRO39) scores, and safety assessment included blood routine, liver and kidney function tests from baseline to the endpoint.

Results: 150 patients were included in the full analysis set for efficacy analysis, including 48, 50, and 52 in groups A, B, and C, respectively. At the endpoint, three regimens significantly reduced serum FT₃ levels (group A, p=0.0027; group B, p < 0.0001; group C, p=0.0028) and FT₄ levels (group A, p < 0.0001; group B, p < 0.0001; group C, p < 0.0001), and the combination of MMI and Pingkang granules markedly reduced serum TRAb levels (p = 0.0014). The thyroid volume in group A was significantly larger than that at baseline at week 12 (p=0.0370), and there were no statistically significant differences in the thyroid volume among groups at week 4 (p=0.7485) and 12 (p=0.1333). STA-PSV values in group B were significantly higher than those in group A at week 4 (p=0.0409). The STA-PSV levels in groups A (p < 0.0001) and C (p=0.0025) were significantly lower than those at baseline at week 4, and STA-PSV levels in all groups were significantly lower than those at baseline at week 12 (group A, p=0.0095; group B, p=0.0138; group C, p=0.0423). Pingkang granule monotherapy significantly ameliorated symptoms related to hyperthyroidism (p < 0.0001), eye (p=0.0490), tiredness (p < 0.0001), cognition (p < 0.0001), depression (p=0.0478), and susceptibility (p=0.0052). No severe adverse events were reported in either group or three regimens showed similar safety.

Conclusions: Pingkang granules significantly reduced serum FT₃, FT₄ and STA-PSV levels, improved ThyPRO39 scores, and lowered serum TRAb levels when combined with MMI in patients with Grave's hyperthyroidism.

Keywords: Chinese herbal medicine; Graves' disease; Hyperthyroidism; Randomized controlled clinical trial.