Methadone Pharmacokinetics in Cardiac Surgery

Wake Forest University (WFU)

Status and phase: Begins enrollment this month; Phase 4

Conditions: Postoperative Pain Management

Treatments: Drug: Split dose of methadone; Drug: Single dose of methadone; Drug: Balanced split dose of methadone

Study type: Interventional

Funder types: Other

Identifiers

NCT07226245

IRB00136746

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 69 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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69 participants in 3 patient groups

Single dose of methadone

Active Comparator group

Description:

Single dose of methadone administered at induction of anesthesia

Treatment:

Drug: Single dose of methadone

Split dose of methadone

Experimental group

Description:

Split dose of methadone post cardiopulmonary bypass

Treatment:

Drug: Split dose of methadone

Balanced split dose of methadone

Experimental group

Description:

Balanced split dose of methadone post cardiopulmonary bypass

Treatment:

Drug: Balanced split dose of methadone