A multicenter, prospective, randomized, double-blind, placebo-controlled clinical trial is currently evaluating the efficacy and safety of Ruanjian Qingmai granules in patients with early symptomatic peripheral artery disease (PAD). The study, led by researchers at the Diagnosis and Treatment Center of Vascular Disease, Shanghai TCM-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, aims to determine if the traditional Chinese medicine formula can improve walking ability and slow the progression of PAD in this patient population.
Background and Rationale
PAD affects over 200 million people worldwide and is characterized by reduced blood flow to the lower extremities, often leading to intermittent claudication, rest pain, and critical limb ischemia. Early symptomatic PAD is challenging to manage, and current treatments, including exercise therapy and vasoactive drugs, have limitations. Ruanjian Qingmai granules, derived from a classical formula, have been used for decades in China to treat PAD, with some evidence suggesting benefits in alleviating ischemic inflammation, improving lipid profiles, and promoting collateral circulation.
Study Design and Methods
The trial plans to enroll approximately 250 participants aged 40 to 80 years across nine hospitals in Shanghai. Participants will be randomized 1:1 to receive either Ruanjian Qingmai granules (6 g twice daily) or a placebo for 16 weeks. The primary efficacy endpoints are changes from baseline in pain-free walking distance and maximum walking distance after 16 weeks. Secondary endpoints include changes in Chinese Medicine Syndrome Score, Walking Impairment Questionnaire (WIQ) score, and 36-Item Short-Form (SF-36) health survey scores. Exploratory endpoints involve assessing changes in carotid/superficial femoral artery intima-media thickness and vascular stiffness, as well as changes in serum levels of inflammatory factors such as IL-1β, IL-6, IL-8, IL-10, CRP, SAA, and TNF-α.
Inclusion and Exclusion Criteria
Eligible participants must meet the diagnostic criteria for PAD according to the European Society of Cardiology guidelines and exhibit symptoms of "blood vessel stasis and obstruction" in Chinese medicine. They should have stable intermittent claudication for at least three months and an ankle-brachial index (ABI) of ≤ 0.9. Exclusion criteria include other conditions affecting walking distance, severe cardiovascular disease, poorly controlled diabetes or hypertension, and the use of prohibited concomitant medications.
Statistical Analysis
The primary efficacy analysis will be based on the full analysis set (FAS), with missing data imputed using the last observation carried forward (LOCF) method. Analysis of variance (ANOVA) will be used to compare the treatment and control groups. Safety will be assessed based on the safety analysis set (SS), which includes all patients who receive at least one dose of the study drug.
Potential Impact
This clinical trial has the potential to provide evidence for an effective treatment option for patients with early symptomatic PAD. If the results are positive, Ruanjian Qingmai granules could offer a new therapeutic strategy to improve walking ability, quality of life, and reduce the progression of PAD in this patient population. The study will also provide insights into the potential anti-inflammatory mechanisms of the granules in PAD.
The trial is expected to conclude by December 31, 2024.
