BuqiTongluo Granule for Ischemic Stroke, Stable Angina Pectoris, Diabetic Peripheral Neuropathy with Qi Deficiency and Blood Stasis Syndrome: Rationale and Novel Basket Design

Abstract

Background: BuqiTongluo (BQTL) granules are herbal phenotypic drugs for Qi deficiency and blood stasis (QDBS) syndrome. Its discovery relied primarily on knowledge of observable phenotypic changes associated with diseases. Although BQTL granules have been widely advocated by Chinese Medicine (CM) practitioners, its use lacks empirical support.Aim of the study: In this basket trial, the efficacy of BQTL granules in multiple diseases that have the QDBS syndrome in common will be compared with placebo.Materials and Methods: The BuqiTongluo granule for Qi deficiency and blood stasis syndrome (BOSS) study is a basket herbal trial (ClinicalTrials.gov, NCT04408261). It will be a double-blinded, randomized, placebo-controlled, parallel, multicenter, clinical trial. In total, 432 patients (1:1:1 ischemic stroke, stable angina pectoris, and diabetic peripheral neuropathy), who meet the operationalized diagnostic criteria for QDBS syndrome, have been recruited and randomized in a ratio of 1:1 to receive 6 weeks’ treatment with BQTL granules or placebo. The primary outcome is the change in the QDBS syndrome score at week 6 from baseline. Secondary outcomes include objective outcome measures for the three diseases and adverse events. Omics will help to understand these responses by molecular events.Conclusion: QDBS syndrome is a common phenotypic marker that was hypothesized to predict whether patients with multiple diseases would respond to this targeted therapy. No previous basket trial has assessed the potential efficacy of an herbal intervention for multiple diseases. The unique promise of the trial is its ability to exploit a disease phenotype to discover novel treatments for three diseases for which the root cause is unknown, complex, or multifactorial, and for which scientific understanding is insufficient to provide valid molecular targets.

Effectiveness and Safety of Fufang Danshen Dripping Pill (Cardiotonic Pill) on Blood Viscosity and Hemorheological Factors for Cardiovascular Event Prevention in Patients with Type 2 Diabetes Mellitus: Systematic Review and Meta-Analysis

“…High blood viscosity, called "blood stasis" in traditional East Asian medicine, was thought to be one of the leading causes of chest pain and cerebral infarction and is listed in the International Classification of Diseases (ICD) code as "blood stasis pattern" or "blood stagnation pattern" [74,75]. This blood stasis pattern is derived from the concept of high blood viscosity and is believed to share similarities with the causes of metabolic and chronic pain diseases [76,77]. In particular, various drugs have been developed to improve blood conditions, including blood viscosity.…”

The key elements and application of a master protocol in the development of the core outcome set

“…9,10 The master protocol has been introduced in China and applied in the design of clinical trials of traditional Chinese medicine (TCM), especially for the same TCM syndrome in different diseases. [11][12][13] An umbrella trial is a design used to study multiple targeted therapies in the context of a single disease, whereas a basket trial is designed to study a single targeted therapy in the context of multiple diseases or disease subtypes. A platform trial is a design used to study multiple targeted therapies in the context of a single disease in a perpetual manner, with therapies allowed to enter or leave the platform based on a decision algorithm.…”

“…It has been applied in clinical cancer research to improve genomic screening efficiency and to increase the speed of drug development and evaluation 9,10 . The master protocol has been introduced in China and applied in the design of clinical trials of traditional Chinese medicine (TCM), especially for the same TCM syndrome in different diseases 11–13 …”

Efficacy and safety of naotaifang capsules for hypertensive cerebral small vessel disease: Study protocol for a multicenter, randomized, double-blind, placebo-controlled clinical trial

“…Based on TCM theory, Qi deficiency and blood stasis (QDBS) is the major mechanism of HT-CSVD (Lin et al, 2021) and cerebral ischemia or ischemic/reperfusion injury. Notably, QDBS is a complex pathological system accompanied by oxygen radical accumulation, inflammation, vascular endothelial damage, and viscera injury, which in turn further promotes the development of QDBS (Bi et al, 2019;Zhang et al, 2020;Liu et al, 2021). According to TCM theory, Qi pushes the blood to circulate in the channels and can produce blood.…”