Cardioplexol™ Demonstrates Safety and Efficacy in Phase 3 Trial for Cardiac Surgery
核心洞察
A pivotal phase 3 non-inferiority trial has confirmed the safety and efficacy of Cardioplexol (搜索)™, a new low-volume cardioplegic solution, compared to standard Buckberg (搜索) blood cardioplegia in cardiac surgeries.
Cardioplexol (搜索)™ showed significant advantages including faster cardiac arrest (11 vs 71 seconds), reduced cross-clamp time, lower defibrillation rates (10% vs 52%), and decreased need for post-operative inotropic support.
Following successful clinical validation, Cardioplexol (搜索)™ received marketing authorization in Switzerland in September 2023 and in 10 European countries in April 2024.
A single-center, randomized phase 3 trial has demonstrated that Cardioplexol (搜索)™, a novel cardioplegic solution, is non-inferior to the standard Buckberg (搜索) blood cardioplegia in protecting the heart during cardiac surgery, while offering several clinical advantages.
The study, conducted at Hospital Hietzing (搜索) in Vienna between 2012 and 2015, enrolled 248 patients undergoing elective coronary artery bypass grafting (CABG), valve replacement/repair, and/or aortic root surgery with heart-lung machine support.
Novel Cardioplegic Solution Shows Promising Results
Cardioplexol (搜索)™ is a ready-to-use, low-volume (100 ml) cardioplegic solution combining four chemical ingredients: potassium chloride, magnesium sulfate heptahydrate, xylitol, and procaine hydrochloride. It was originally developed to match the concept of Minimal invasive Extra Corporeal Circulation (MiECC).
The primary endpoint of the study was peak troponin-T (搜索) (TnT) levels during the first 24 hours following myocardial reperfusion, a recognized marker for myocardial preservation and cardioplegia effectiveness. Results from the per-protocol analysis of 226 patients (100 Cardioplexol (搜索)™, 126 Buckberg (搜索)) showed similar peak TnT values between the groups (0.77 vs. 0.78 ng/ml), confirming non-inferiority of Cardioplexol™.
Significant Clinical Advantages
Beyond meeting the primary endpoint, Cardioplexol (搜索)™ demonstrated several significant advantages over the Buckberg (搜索) solution:
- Faster cardiac arrest: 11 seconds vs. 71 seconds (p<0.001)
- Shorter cross-clamp time: 51.2 minutes vs. 60.7 minutes (p<0.001)
- Lower defibrillation rate after reperfusion: 10% vs. 52% (p<0.001)
- Reduced need for post-operative inotropic support (p<0.001)
- Shorter ICU stay: 38.1 hours vs. 44.0 hours (p=0.110)
Dr. Hendrik Tevaearai Stahel, inventor of Cardioplexol (搜索)™ and co-founder of Swiss Cardio Technologies AG, commented: "The rapid cardiac arrest critically limits the metabolic demands of the non-perfused heart and improves myocardial integrity during the ischemic period."
Practical Benefits in Surgical Settings
Cardioplexol (搜索)™'s administration differs significantly from standard solutions. It requires a limited volume with rapid direct injection by the surgeon, resulting in immediate cardiac arrest without the need for repeated administration every 20 minutes. In the study, 63% of Cardioplexol™ patients required only a single dose, while Buckberg (搜索) patients needed up to seven doses.
The duration and volume of injections were also markedly reduced with Cardioplexol (搜索)™. The first dose took 18.6 seconds versus 250.6 seconds for Buckberg (搜索), with volumes of 102.8 ml versus 271.4 ml respectively.
Safety Profile
Safety parameters were comparable between both groups, with no significant differences in adverse events. Notably, 30-day mortality was lower in the Cardioplexol (搜索)™ group (1 patient) compared to the Buckberg (搜索) group (5 patients).
Despite containing high equivalent potassium, serum potassium values remained within normal range after Cardioplexol (搜索)™ administration, and were actually slightly lower than in the Buckberg (搜索) group. This is likely because the low volume remains confined to the coronary system.
Path to Market Approval
Following this pivotal study, regulatory authorities requested an additional study to validate a training protocol for surgeons new to using Cardioplexol (搜索)™, as administration technique was identified as critical to safety. This complementary study was successfully completed, leading to marketing authorization for Cardioplexol™ in Switzerland in September 2023 and in 10 European countries in April 2024.
Study Limitations
The authors acknowledge several limitations, including the single-center design and varied surgical indications. However, subgroup analyses confirmed similar results regardless of procedure type, patient gender, or age group.
The study results represent a significant advancement in cardiac surgery, offering a cardioplegic solution that maintains myocardial protection while potentially improving surgical efficiency and patient outcomes.