比较两种枳术丸治疗脾虚气滞型功能性消化不良的疗效：一项随机分组序贯比较试验。

To compare the efficacy of two kinds of Zhizhu pills in the treatment of functional dyspepsia of spleen-deficiency and qi-stagnation syndrome: a randomized group sequential comparative trial.

机构信息

Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, No. 16 Nanxiaojie, Dongzhimen nei, Beijing, 100700, China.

出版信息

BMC Gastroenterol. 2011 Jul 15;11:81. doi: 10.1186/1471-230X-11-81.

DOI:10.1186/1471-230X-11-81

PMID:21762493

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3160401/

Abstract

BACKGROUND

In Traditional Chinese Medicine (TCM) theory, functional dyspepsia (FD) can be divided into different syndromes according to different clinical symptoms and signs, and the most common one is spleen-deficiency and qi-stagnation syndrome that can be treated by Chinese traditional patent medicine--two kinds of Zhizhu pills, between which the primary difference in ingredients is that one contains immature orange fruit of Citrus aurantium L.(IFCA) and the other contains that of Citrus sinensis Osbeck (IFCS). The trial's objective was to compare the efficacy of two kinds of Zhizhu pills on symptom changes in patients with FD of spleen-deficiency and qi-stagnation syndrome.

METHODS

A randomized, group sequential, double-blinded, multicenter trial was conducted in patients with FD of spleen-deficiency and qi-stagnation syndrome at 3 hospitals in Beijing between June 2003 and May 2005. Participants were randomly allocated into two groups (IFCA group and IFCS group) in a 1:1 ratio, and respectively took one of the two kinds of Zhizhu pills orally, 6 g each time, 3 times a day, for 4 weeks. Statistical analysis was performed with use of a group sequential method, the triangular test (TT).

RESULTS

A total of 163 patients were randomized, and 3 patients were excluded from analysis because of early dropouts, leaving 160 patients (IFCA group: n = 82; IFCS group: n = 78) for statistical analysis. Three interim analyses were done after 62, 116, and 160 patients had completed their 4-week treatment, respectively. At the third interim analysis, the sample path crossed the upper boundary and the trial was stopped, the cure-markedly effective rates were 45% for IFCS group and 67% for IFCA group, respectively, the one-sided p-value was 0.0036, the median unbiased estimate of the odds ratio (OR) for the benefit of IFCA relative to IFCS was 2.91 with 95%CI: 1.40 to 6.06.No adverse events were observed in the two groups.

CONCLUSIONS

Zhizhu pills containing IFCA was superior to Zhizhu pills containing IFCS in the treatment of FD of spleen-deficiency and qi-stagnation syndrome. The application of group sequential analysis in clinical trials of TCM may offer some financial and ethical benefits.

TRIAL REGISTRATION

Chinese Clinical Trial Registry (ChiCTR): ChiCTR-TRC-00000485.

摘要

背景

在中医理论中，功能性消化不良（FD）可根据不同的临床症状和体征分为不同的证型，其中最常见的是脾虚气滞证，可采用中药传统专利药——两种枳术丸进行治疗，其成分的主要区别在于一种含有不成熟的酸橙果实（IFCA），另一种含有甜橙果实（IFCS）。本试验的目的是比较两种枳术丸对脾虚气滞型 FD 患者症状变化的疗效。

方法

采用随机、分组序贯、双盲、多中心试验，于 2003 年 6 月至 2005 年 5 月在北京的 3 家医院对脾虚气滞型 FD 患者进行，将患者按 1：1 比例随机分配到两组（IFCA 组和 IFCS 组），分别口服两种枳术丸，每次 6g，每日 3 次，疗程 4 周。采用群组序贯法，即三角检验（TT）进行统计分析。

结果

共纳入 163 例患者，3 例因提前退出而被排除分析，最终 160 例患者（IFCA 组：n=82；IFCS 组：n=78）纳入统计分析。在 62、116 和 160 例患者完成 4 周治疗后分别进行了 3 次中期分析。第 3 次中期分析时，样本路径越过了上限，试验停止，IFCS 组的治愈率和显效率分别为 45%和 67%，单侧 p 值为 0.0036，IFCA 相对 IFCS 获益的优势比（OR）的中位数无偏估计值为 2.91，95%CI：1.40 至 6.06。两组均未观察到不良事件。