Evaluating Pharmacokinetics of Three Methadone Dosing Strategies During Cardiac Surgery With Cardiopulmonary Bypass
试验速览
- 阶段
- 4 期
- 状态
- 撤回
- 入组人数
- 69
- 试验地点
- 1
- 主要终点
- Plasma methadone concentration (ng/mL) 10 min post initial dose
研究概览
简要总结
Cardiac surgery frequently leads to significant postoperative pain, with multiple different drug regimens being utilized (both opioid and non-opioid) in an attempt to alleviate this surgical pain. Methadone is currently one of the drugs that is being utilized to help control the pain. It can be given during and/or after surgery. This study hopes to identify the optimal dose of methadone to use to treat this surgical pain.
详细描述
The uncertainty regarding optimal methadone dosing and the necessity of post-cardiopulmonary bypass (CPB) supplementation provides a compelling rationale for this study. Specifically, it remains unknown whether a single higher initial dose of methadone can adequately maintain analgesic plasma concentrations throughout cardiac surgery and recovery, or if a split-dosing strategy administering a lower initial dose followed by an additional dose post-CPB might offer similar or improved analgesic outcomes with fewer side effects. This study will evaluate pharmacokinetics of methadone using three different dosing strategies in patients undergoing cardiac surgery with CPB.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Elective cardiac surgery requiring median sternotomy and cardiopulmonary bypass (CABG, valve, combined CABG/valve surgeries)
- •Anticipated extubation within 12 hours postoperatively
- •No prior opioid use within 30 days of surgery
- •Ability to provide informed consent
排除标准
- •Severe liver or kidney dysfunction (Child-Pugh class B/C, eGFR <30 mL/min/1.73m², creatinine >2 mg/dL, dialysis)
- •Allergy to methadone or fentanyl
- •Use of CYP3A4 inducers (rifampin, phenytoin, carbamazepine), CYP3A4 inhibitors (ketoconazole, erythromycin, clarithromycin, itraconazole), SSRIs (fluoxetine, sertraline, paroxetine, citalopram, escitalopram, fluvoxamine)
- •Body mass index >40 kg/m²
- •Corrected QT interval interval >500 milliseconds
- •Intubation anticipated >12 hours
- •History of illicit drug use or alcohol or opioid abuse use disorder within last 12 months
- •Mechanical circulatory support, heart transplant, deep hypothermic circulatory arrest procedures
- •Left Ventricular Ejection Fraction <30%
- •Pulmonary disease requiring oxygen therapy
- •Preoperative inotropic support or intra-aortic balloon pump
- •Emergency surgery
- •Postoperative regional anesthesia
- •Hemofiltration during cardiopulmonary bypass
研究组 & 干预措施
Single dose of methadone
Single dose of methadone administered at induction of anesthesia
干预措施: Single dose of methadone (Drug)
Split dose of methadone
Split dose of methadone post cardiopulmonary bypass
干预措施: Split dose of methadone (Drug)
Balanced split dose of methadone
Balanced split dose of methadone post cardiopulmonary bypass
干预措施: Balanced split dose of methadone (Drug)
结局指标
主要结局
Plasma methadone concentration (ng/mL) 10 min post initial dose
时间窗: 10 minutes
Plasma methadone concentration will be measured 10 minutes post initial methadone dose
Plasma methadone concentration (ng/mL) 30 min post initial dose
时间窗: 30 minutes
Plasma methadone concentration will be measured 30 minutes post initial methadone dose pre cardiopulmonary bypass
Plasma methadone concentration (ng/mL) 60 min post initial dose
时间窗: 60 minutes
Plasma methadone concentration will be measured 60 minutes post initial methadone dose pre cardiopulmonary bypass
Plasma methadone concentration (ng/mL) 10 min post start of cardiopulmonary bypass
时间窗: 10 minutes
Plasma methadone concentration will be measured 10 minutes after cardiopulmonary bypass started
Plasma methadone concentration (ng/mL) 30 min post start of cardiopulmonary bypass
时间窗: 30 minutes
Plasma methadone concentration will be measured 30 minutes after cardiopulmonary bypass started
Plasma methadone concentration (ng/mL) 60 min post start of cardiopulmonary bypass
时间窗: 60 minutes
Plasma methadone concentration will be measured 60 minutes after cardiopulmonary bypass started
Plasma methadone concentration (ng/mL) 10 min post cardiopulmonary bypass completion
时间窗: 10 minutes
Plasma methadone concentration will be measured 10 minutes after cardiopulmonary bypass ended
Plasma methadone concentration (ng/mL) 120 min post start of cardiopulmonary bypass
时间窗: 120 minutes
Plasma methadone concentration will be measured 120 minutes after cardiopulmonary bypass started
Plasma methadone concentration (ng/mL) before first analgesic request
时间窗: up to 72 hours
Plasma methadone concentration will be measured at the time of first analgesic request by participant
Plasma methadone concentration (ng/mL) 3 hours post Intensive Care Unit arrival
时间窗: 3 hours
Plasma methadone concentration will be measured 3 hours post Intensive Care Unit arrival
Plasma methadone concentration (ng/mL) 12 hours post Intensive Care Unit arrival
时间窗: 12 hours
Plasma methadone concentration will be measured 12 hours post Intensive Care Unit arrival
Plasma methadone concentration (ng/mL) 24 hours post Intensive Care Unit arrival
时间窗: 24 hours
Plasma methadone concentration will be measured 24 hours post Intensive Care Unit arrival
次要结局
- pain intensity score(2, 4, 8, 12, 24, 48, and 72 hours postoperatively and month 3)
- patient global impression of change(24, 48, and 72 hours after removal of the breathing tube)
- postoperative opioid consumption(up 72 hours postop)
- duration of postoperative mechanical ventilation(up to 72 hours postop)
- time of ambulation(up to 48 hours postop)
- length of Intensive Care Unit stay(up to 3 days postop)
- length of hospital length stay(up to 7 days postop)