Yongxing Jiang1, Jingxue Fan1, Yong Li2, Guodong Wu1, Yuanqi Wang1, Jiemei Yang1, Mengjiao Wang2, Zhengyu Cao1, Qiannan Li1, Hui Wang1, Zhengyan Zhang1, Yu Wang1, Bicheng Li1, Fengyu Sun3, Haiyu Zhang3, Zhiguo Zhang4, Kang Li5, Ye Tian6. 1. Department of Cardiology, The First Affiliated Hospital, Cardiovascular Institute, Harbin Medical University, Harbin, PR China. 2. Department of PET/CT, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, PR China. 3. Department of Cardiology, The First Affiliated Hospital, Cardiovascular Institute, Harbin Medical University, Harbin, PR China; Department of Epidemiology and Biostatistics, Harbin Medical University, Harbin, PR China. 4. Laboratory of Photo- and Sono-theranostic Technologies and Condensed Matter Science and Technology Institute, Harbin Institute of Technology, Harbin, PR China. 5. Department of Epidemiology and Biostatistics, Harbin Medical University, Harbin, PR China. 6. Department of Cardiology, The First Affiliated Hospital, Cardiovascular Institute, Harbin Medical University, Harbin, PR China; Department of Pathophysiology and Key Laboratory of Cardiovascular Pathophysiology, Harbin Medical University, Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education, Harbin, PR China. Electronic address: yetian@ems.hrbmu.edu.cn.
Abstract
BACKGROUND: Inflammation is actively involved in the clinical manifestation of peripheral artery disease (PAD). Sonodynamic therapy (SDT), a novel non-invasive, plaque-based, macrophage-targeted anti-inflammatory regimen for atherosclerosis has the potential to improve walking performance by reducing plaque inflammation. METHODS: This phase-2, randomized, sham-controlled, double-blind clinical trial enrolled 32 participants with symptomatic femoropopliteal PAD. The primary outcome was the 30-day change in the target-to-background ratio (TBR) within the most diseased segment (MDS) of the femoropopliteal artery assessed through positron emission tomography/computed tomography (PET/CT). The secondary outcomes were changes in walking performance, limb perfusion, lesional morphology and quality of life measurements. RESULTS:The mean age was 64.7 years and 63% were male. Thirty-one completed follow-up. SDT significantly decreased the MDS TBR by 0.53 (95% CI, -0.70 to -0.36, P < 0.001) compared with control. Furthermore, SDT increased peak walking time by 118.6 s (95% CI, 74.3 to 163.0, P < 0.001), increased ankle-brachial index by 0.11 (95% CI, 0.07 to 0.14, P < 0.001), decreased lesional diameter and area stenosis by 7.2% (95% CI, -8.6 to -4.5, P < 0.001) and 9.6% (95% CI, -24.5 to -5.3, P = 0.005), respectively, and increased the walking speed score of the Walking Impairment Questionnaire by 16.1 (95% CI, 2.6 to 29.5, P = 0.021) and the physical functioning score of the 36-item Short-Form Health Survey by 10.0 (95% CI, 5.0 to 20.0, P = 0.003) compared with control. These improvements were maintained in the SDT group up to 6-month. CONCLUSIONS:SDT rapidly reduced plaque inflammation and improved walking performance among patients with symptomatic PAD. TRIAL REGISTRATION: Clinical Trials NCT03457662.
RCT Entities:
BACKGROUND:Inflammation is actively involved in the clinical manifestation of peripheral artery disease (PAD). Sonodynamic therapy (SDT), a novel non-invasive, plaque-based, macrophage-targeted anti-inflammatory regimen for atherosclerosis has the potential to improve walking performance by reducing plaque inflammation. METHODS: This phase-2, randomized, sham-controlled, double-blind clinical trial enrolled 32 participants with symptomatic femoropopliteal PAD. The primary outcome was the 30-day change in the target-to-background ratio (TBR) within the most diseased segment (MDS) of the femoropopliteal artery assessed through positron emission tomography/computed tomography (PET/CT). The secondary outcomes were changes in walking performance, limb perfusion, lesional morphology and quality of life measurements. RESULTS: The mean age was 64.7 years and 63% were male. Thirty-one completed follow-up. SDT significantly decreased the MDS TBR by 0.53 (95% CI, -0.70 to -0.36, P < 0.001) compared with control. Furthermore, SDT increased peak walking time by 118.6 s (95% CI, 74.3 to 163.0, P < 0.001), increased ankle-brachial index by 0.11 (95% CI, 0.07 to 0.14, P < 0.001), decreased lesional diameter and area stenosis by 7.2% (95% CI, -8.6 to -4.5, P < 0.001) and 9.6% (95% CI, -24.5 to -5.3, P = 0.005), respectively, and increased the walking speed score of the Walking Impairment Questionnaire by 16.1 (95% CI, 2.6 to 29.5, P = 0.021) and the physical functioning score of the 36-item Short-Form Health Survey by 10.0 (95% CI, 5.0 to 20.0, P = 0.003) compared with control. These improvements were maintained in the SDT group up to 6-month. CONCLUSIONS: SDT rapidly reduced plaque inflammation and improved walking performance among patients with symptomatic PAD. TRIAL REGISTRATION: Clinical Trials NCT03457662.