Intranasal Dexmedetomidine and Perioperative Myocardial Injury in Patients Having Percutaneous Coronary Interventions: A Single-Center, Prospective Randomized Controlled Pilot Study
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 140
- 试验地点
- 1
- 主要终点
- Composite incidence of perioperative myocardial injury and myocardial infarction
研究概览
简要总结
PCI is the standard treatment for CAD, yet perioperative myocardial injury occurs frequently in nearly 40% of patients. Perioperative stress and sympathetic overactivation break myocardial oxygen balance and lead to cardiac damage, which further raises short-term cardiovascular events and long-term mortality risks. Dexmedetomidine exerts cardioprotective effects by inhibiting sympathetic excitation, though intravenous use carries risks of hypotension and bradycardia. Intranasal dexmedetomidine shows equivalent efficacy with fewer side effects and better patient compliance. Since no standard perioperative anesthesia regimen exists for elective PCI patients and the clinical benefits of dexmedetomidine remain unconfirmed, this pilot study is designed to test the feasibility and safety of intranasal dexmedetomidine spray before launching large formal RCTs.
详细描述
Coronary heart disease (CHD) remains a major global health burden. Percutaneous coronary intervention (PCI) has become a cornerstone treatment for CHD, effectively reducing mortality. Despite its success, perioperative myocardial injury (PMI) is a frequent complication, occurring in 5-30% of patients, depending on the definition and sensitivity of cardiac biomarkers. PMI ranges from a mild, asymptomatic increase in high-sensitivity cardiac troponin (hs-cTn) to overt myocardial infarction. Even minor elevations in troponin are independently associated with increased 30-day and long-term major adverse cardiovascular events (MACE), as well as higher rates of stent thrombosis and restenosis. The pathophysiology of PMI is multifactorial, including distal embolization, side-branch occlusion, coronary dissection, and, importantly, an imbalance between myocardial oxygen supply and demand during the procedure.
Sedation is commonly used during PCI to relieve anxiety, pain, and stress; however, the choice of sedative and its impact on myocardial outcomes remain controversial. Dexmedetomidine, a highly selective α2-adrenoceptor agonist, provides sedation with minimal respiratory depression and has shown potential cardioprotective effects in preclinical and clinical studies, possibly through reducing sympathetic tone, decreasing myocardial oxygen consumption, and attenuating inflammatory and oxidative stress responses. Intranasal administration offers a non-invasive, convenient route with rapid absorption, making it an attractive option for premedication. Nevertheless, robust evidence from large-scale, multicenter randomized controlled trials is lacking.
This trail is designed to evaluate whether preoperative intranasal dexmedetomidine reduces the incidence of perioperative myocardial injury and myocardial infarction in patients undergoing elective PCI compared with placebo.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged between 18 and 85 years old;
- •Subjects are fully informed of the risks, benefits and alternative treatment regimens of intranasal dexmedetomidine administration. Written informed consent is signed by the subject themselves or their legal representative prior to any study-related procedures;
- •Confirmed diagnosis of coronary artery disease with objective evidence of myocardial ischemia or silent myocardial ischemia, and indications for elective percutaneous coronary intervention (PCI);
- •American Society of Anesthesiologists (ASA) physical status classification II to III (patients with mild to severe systemic underlying diseases; ordinary physical activities are markedly limited, yet mild daily activities can be performed).
排除标准
- •Subjects with hypersensitivity or contraindications to dexmedetomidine, including severe sinus bradycardia (resting heart rate <50 beats per minute), sick sinus syndrome, and second-degree or higher atrioventricular block without pacemaker implantation;
- •Severe cardiac dysfunction (left ventricular ejection fraction <40%), New York Heart Association (NYHA) class III-IV heart failure, cardiogenic shock, or hemodynamic instability;
- •Poorly controlled hypertension (systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg), or hypotension (systolic blood pressure <90 mmHg);
- •Coexisting obstructive sleep apnea hypopnea syndrome (OSAHS);
- •Body mass index (BMI) >30 kg/m²;
- •Use of agents that may interfere with the study drug within 1 week before surgery, including α₂ adrenergic receptor agonists (e.g., clonidine), receptor antagonists, and tricyclic antidepressants;
- •Cognitive assessment cannot be completed due to language, visual or hearing impairment;
- •Hepatic or renal insufficiency (alanine aminotransferase, aspartate aminotransferase, or serum creatinine exceeding 3 times the upper limit of normal reference values);
- •Nasal anatomical abnormalities that preclude intranasal spray administration;
- •Pregnant or breastfeeding women;
- •Participation in other conflicting clinical trials.
研究组 & 干预措施
Normal saline Group
The subjects were given an equal volume of normal saline intranasally, which contained no active ingredient.
干预措施: Normal saline (Drug)
Dexmedetomidine Group
The subjects received intranasal dexmedetomidine (100 μg, sprayed equally into both nostrils, two sprays per nostril) 15 minutes before surgery in the preoperative preparation area.
干预措施: Intranasal Dexmedetomidine (Drug)
结局指标
主要结局
Composite incidence of perioperative myocardial injury and myocardial infarction
时间窗: from the end of surgery to 48 hours after surgery
Perioperative Myocardial Injury and Perioperative Myocardial Infarction: As defined by the Fourth Universal Definition of Myocardial Infarction
Incidence of perioperative myocardial injury
时间窗: From the end of surgery to 48 hours after surgery
Definition of myocardial injury: In patients with a normal baseline cTn concentration (≤99th percentile upper reference limit \[URL\]), postoperative cTn elevation exceeding the 99th percentile URL; In patients with an elevated baseline cTn concentration (\>99th percentile URL) that was stable or decreasing, a postoperative cTn increase of \>20% from baseline, with an absolute value exceeding the 99th percentile URL.
次要结局
- Incidence of perioperative myocardial injury(from the end of surgery to 48 hours after surgery)
- Incidence of perioperative myocardial infarction(from the end of surgery to 48 hours after surgery)
- Incidence of severe perioperative myocardial injury(from the end of surgery to 48 hours after surgery)
- Incidence of major adverse cardiac and cerebrovascular events (MACCE) within 4 and 12 weeks after surgery(4 and 12 weeks after surgery)
- Incidence of unplanned hospital readmission within 4 and 12 weeks after surgery(4 and 12 weeks after surgery)
- Variability of mean arterial pressure and systolic blood pressure(From operating room admission to 24 hours postoperatively)
- Change in perioperative anxiety scores(Before intervention; after intervention but before surgery; 1 day after surgery)
- Change in perioperative cardiac enzyme levels(Baseline, 6 hours after surgery, 24 hours after surgery or before discharge)
- Postoperative pain scores(immediately after surgery and one first day after surgery)
- Sleep quality scores on postoperative day 1 and day 2(baseline, 1 day after surgery, 2day after surgery)
- Length of hospital stay(Through patients discharge, an average of 2 days after surgery)
- Hospitalization costs(Through patients discharge, an average of 2 days after surgery)
- Quality of life scores at 4 and 12 weeks after surgery(Baseline, 4 and 12 weeks after surgery)
- Acute adverse reactions(from intervention to 6 hours after surgery)
- Intraoperative hypotension(From intervention to end of surgery)
- Incidence of intraoperative hypoxemia(From intervention to end of surgery)
- Incidence of severe bradycardia(From intervention to 6 hours after surgery)
- Utilization rate of vasoactive drugs(From intervention to 6 hours after surgery)
- Incidence of major perioperative myocardial injury(From the end of surgery to 48 hours after surgery)
- Composite outcome at 30 days after PCI(30 days after surgery)
- Blood pressure stability(From the start of the procedure to the end of the procedure)
- Perioperative myocardial oxygen consumption(From the start of the procedure to the end of the procedure)