Methadone Pharmacokinetics in Cardiac Surgery

NCT07226245 | Not Yet Recruiting Phase 4 FDA Drug

• 1 other identifier: IRB00136746
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Postoperative Pain Management

Keywords

methadone pharmacokinetics; cardiac surgery; pain management; cardiac surgery recovery; methadone

Outcome Measures

Primary Outcomes (12)

• Plasma methadone concentration (ng/mL) 10 min post initial dose

  Plasma methadone concentration will be measured 10 minutes post initial methadone dose

  10 minutes

• Plasma methadone concentration (ng/mL) 30 min post initial dose

  Plasma methadone concentration will be measured 30 minutes post initial methadone dose pre cardiopulmonary bypass

  30 minutes

• Plasma methadone concentration (ng/mL) 60 min post initial dose

  Plasma methadone concentration will be measured 60 minutes post initial methadone dose pre cardiopulmonary bypass

  60 minutes

• Plasma methadone concentration (ng/mL) 10 min post start of cardiopulmonary bypass

  Plasma methadone concentration will be measured 10 minutes after cardiopulmonary bypass started

  10 minutes

• Plasma methadone concentration (ng/mL) 30 min post start of cardiopulmonary bypass

  Plasma methadone concentration will be measured 30 minutes after cardiopulmonary bypass started

  30 minutes

• Plasma methadone concentration (ng/mL) 60 min post start of cardiopulmonary bypass

  Plasma methadone concentration will be measured 60 minutes after cardiopulmonary bypass started

  60 minutes

• Plasma methadone concentration (ng/mL) 10 min post cardiopulmonary bypass completion

  Plasma methadone concentration will be measured 10 minutes after cardiopulmonary bypass ended

  10 minutes

• Plasma methadone concentration (ng/mL) 120 min post start of cardiopulmonary bypass

  Plasma methadone concentration will be measured 120 minutes after cardiopulmonary bypass started

  120 minutes

• Plasma methadone concentration (ng/mL) before first analgesic request

  Plasma methadone concentration will be measured at the time of first analgesic request by participant

  up to 72 hours

• Plasma methadone concentration (ng/mL) 3 hours post Intensive Care Unit arrival

  Plasma methadone concentration will be measured 3 hours post Intensive Care Unit arrival

  3 hours

• Plasma methadone concentration (ng/mL) 12 hours post Intensive Care Unit arrival

  Plasma methadone concentration will be measured 12 hours post Intensive Care Unit arrival

  12 hours

• Plasma methadone concentration (ng/mL) 24 hours post Intensive Care Unit arrival

  Plasma methadone concentration will be measured 24 hours post Intensive Care Unit arrival

  24 hours

Secondary Outcomes (7)

• 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

Study Arms (3)

Single dose of methadone

ACTIVE COMPARATOR

Single dose of methadone administered at induction of anesthesia

Drug: Single dose of methadone

Split dose of methadone

EXPERIMENTAL

Split dose of methadone post cardiopulmonary bypass

Drug: Split dose of methadone

Balanced split dose of methadone

EXPERIMENTAL

Balanced split dose of methadone post cardiopulmonary bypass

Drug: Balanced split dose of methadone

Interventions

Single dose of methadone DRUG

Single dose of methadone 0.3 mg/kg actual body weight (max 30 mg) administered at induction of anesthesia

Single dose of methadone

Split dose of methadone DRUG

Split dose of methadone 0.2 mg/kg actual body weight at induction and 0.1 mg/kg actual body weight post cardiopulmonary bypass

Split dose of methadone

Balanced split dose of methadone DRUG

Balanced split dose of methadone 0.15 mg/kg actual body weight at induction and 0.15 mg/kg actual body weight post cardiopulmonary bypass

Balanced split dose of methadone

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead

Study Sites (1)

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

MeSH Terms

Conditions

Agnosia

Interventions

Methadone

Condition Hierarchy (Ancestors)

Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ketones; Organic Chemicals

Study Officials

• Ettore Crimi, MD

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ettore Crimi, MD

CONTACT

336-716-4498; ettore.crimi@advocatehealth.org

Lynnette Harris, BSN

CONTACT

336-716-8791; lynnette.harris@advocatehealth.org

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2025
• First Posted: November 10, 2025
• Study Start: May 1, 2026
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: March 27, 2026

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)