Methadone Pharmacokinetics in Cardiac Surgery

August 13, 2026 updated by: Wake Forest University Health Sciences

Evaluating Pharmacokinetics of Three Methadone Dosing Strategies During Cardiac Surgery With Cardiopulmonary Bypass

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed 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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest University Health Sciences

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Single dose of methadone
Single dose of methadone administered at induction of anesthesia
Drug: Single dose of methadone
Single dose of methadone 0.3 mg/kg actual body weight (max 30 mg) administered at induction of anesthesia
Experimental: Split dose of methadone
Split dose of methadone post cardiopulmonary bypass
Drug: Split dose of methadone
Split dose of methadone 0.2 mg/kg actual body weight at induction and 0.1 mg/kg actual body weight post cardiopulmonary bypass
Experimental: Balanced split dose of methadone
Balanced split dose of methadone post cardiopulmonary bypass
Drug: Balanced split dose of methadone
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Plasma methadone concentration (ng/mL) 10 min post initial dose
Time Frame: 10 minutes
Plasma methadone concentration will be measured 10 minutes post initial methadone dose
10 minutes
Plasma methadone concentration (ng/mL) 30 min post initial dose
Time Frame: 30 minutes
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
Time Frame: 60 minutes
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
Time Frame: 10 minutes
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
Time Frame: 30 minutes
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
Time Frame: 60 minutes
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
Time Frame: 10 minutes
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
Time Frame: 120 minutes
Plasma methadone concentration will be measured 120 minutes after cardiopulmonary bypass started
120 minutes
Plasma methadone concentration (ng/mL) before first analgesic request
Time Frame: up to 72 hours
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
Time Frame: 3 hours
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
Time Frame: 12 hours
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
Time Frame: 24 hours
Plasma methadone concentration will be measured 24 hours post Intensive Care Unit arrival
24 hours

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
pain intensity score
Time Frame: 2, 4, 8, 12, 24, 48, and 72 hours postoperatively and month 3
Pain intensity score will be measured using the visual analog scale. Scores will be measured on a scale of 0-10, with 0=no pain and 10=most severe pain
2, 4, 8, 12, 24, 48, and 72 hours postoperatively and month 3
patient global impression of change
Time Frame: 24, 48, and 72 hours after removal of the breathing tube
Patient Global Impression of Change will be used to assess patient-perceived analgesic effectiveness and overall postoperative recovery. Total score range is 1-7 with a higher score indicating considerable improvement with treatment.
24, 48, and 72 hours after removal of the breathing tube
postoperative opioid consumption
Time Frame: up 72 hours postop
total postoperative opioid consumption in morphine milligram equivalents
up 72 hours postop
duration of postoperative mechanical ventilation
Time Frame: up to 72 hours postop
number of minutes with postoperative mechanical ventilation
up to 72 hours postop
time of ambulation
Time Frame: up to 48 hours postop
number of minutes until patient first ambulates after surgery
up to 48 hours postop
length of Intensive Care Unit stay
Time Frame: up to 3 days postop
number of hours spent in Intensive Care Unit
up to 3 days postop
length of hospital length stay
Time Frame: up to 7 days postop
number of days spent in hospital
up to 7 days postop

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Wake Forest University Health Sciences

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Ettore Crimi, MD, Wake Forest University Health Sciences

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 30, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 30, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 4, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 6, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 10, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 17, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 13, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IRB00136746

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

study results will be shared instead of individual patient data

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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