Postoperative Pain ManagementPhase 4NCT07226245
Methadone Pharmacokinetics in Cardiac Surgery
A Phase 4 study testing Single dose of methadone, Split dose of methadone and Balanced split dose of methadone in people with Postoperative Pain Management, run by Wake Forest University Health Sciences.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Postoperative Pain Management
- What is being tested?
- Single dose of methadone, Split dose of methadone and Balanced split dose of methadone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Sep 2026to 30 Dec 2026
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
About this study
Official title: 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.
Read the 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.
- Conditions
- Postoperative Pain Management
- Being tested
- Single dose of methadone, Split dose of methadone, Balanced split dose of methadone
- Keywords
- methadone pharmacokinetics, cardiac surgery, pain management, cardiac surgery recovery, methadone
- Medical subject headings
- Agnosia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Single dose of methadoneDrug
Single dose of methadone 0.3 mg/kg actual body weight (max 30 mg) administered at induction of anesthesia
Split dose of methadoneDrug
Split dose of methadone 0.2 mg/kg actual body weight at induction and 0.1 mg/kg actual body weight post cardiopulmonary bypass
Balanced split dose of methadoneDrug
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
| Study group | Role | What they receive |
|---|---|---|
| Single dose of methadone | Active comparator | Single dose of methadone administered at induction of anesthesia Receives: Drug: Single dose of methadone |
| Split dose of methadone | Experimental | Split dose of methadone post cardiopulmonary bypass Receives: Drug: Split dose of methadone |
| Balanced split dose of methadone | Experimental | Balanced split dose of methadone post cardiopulmonary bypass Receives: Drug: Balanced split dose of methadone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma methadone concentration (ng/mL) 10 min post initial dose
Plasma methadone concentration will be measured 10 minutes post initial methadone dose
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 24 hours
Secondary outcomes (7)
pain intensity score
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
Measured: 2, 4, 8, 12, 24, 48, and 72 hours postoperatively and month 3
patient global impression of change
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.
Measured: 24, 48, and 72 hours after removal of the breathing tube
postoperative opioid consumption
total postoperative opioid consumption in morphine milligram equivalents
Measured: up 72 hours postop
duration of postoperative mechanical ventilation
number of minutes with postoperative mechanical ventilation
Measured: up to 72 hours postop
time of ambulation
number of minutes until patient first ambulates after surgery
Measured: up to 48 hours postop
length of Intensive Care Unit stay
number of hours spent in Intensive Care Unit
Measured: up to 3 days postop
length of hospital length stay
number of days spent in hospital
Measured: up to 7 days postop
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Nov 2025
- Study startSep 2026 (estimated)
- Primary completion30 Dec 2026 (estimated)
- Study completion30 Dec 2026 (estimated)
Why it stopped: loss of funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Postoperative Pain ManagementStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ettore Crimi, MD, Principal investigator, Wake Forest University Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07226245
- Sponsor's protocol ID
- IRB00136746
- Status last verified
- Aug 2026
- First submitted
- 4 Nov 2025
- Last updated
- 17 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: study results will be shared instead of individual patient data
Study at a glance
From the registry record, last updated by the sponsor on 17 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluating Pharmacokinetics of Three Methadone Dosing Strategies During Cardiac Surgery With Cardiopulmonary Bypass
- ClinicalTrials.gov ID
- NCT07226245
- Acronym / sponsor ID
- IRB00136746
- Conditions
- Postoperative Pain Management
- Keywords
- methadone pharmacokinetics, cardiac surgery, pain management, cardiac surgery recovery, methadone
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: loss of funding
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Study start
- Sep 2026 (estimated)
- Primary completion
- 30 Dec 2026 (estimated)
- Study completion
- 30 Dec 2026 (estimated)
- First posted
- 10 Nov 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Single dose of methadone | Active comparator | Drug: Single dose of methadoneSingle dose of methadone administered at induction of anesthesia |
| Split dose of methadone | Experimental | Drug: Split dose of methadoneSplit dose of methadone post cardiopulmonary bypass |
| Balanced split dose of methadone | Experimental | Drug: Balanced split dose of methadoneBalanced split dose of methadone post cardiopulmonary bypass |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Single dose of methadoneSingle dose of methadone 0.3 mg/kg actual body weight (max 30 mg) administered at induction of anesthesia | Drug | Single dose of methadone |
| Split dose of methadoneSplit dose of methadone 0.2 mg/kg actual body weight at induction and 0.1 mg/kg actual body weight post cardiopulmonary bypass | Drug | Split dose of methadone |
| Balanced split dose of methadoneBalanced split dose of methadone 0.15 mg/kg actual body weight at induction and 0.15 mg/kg actual body weight post cardiopulmonary bypass | Drug | Balanced split dose of methadone |
Primary outcome
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
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
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
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
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
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
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
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
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
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
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
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
7 secondary outcomes
pain intensity score
Time frame: 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
postoperative opioid consumption
Time frame: up 72 hours postop
duration of postoperative mechanical ventilation
Time frame: up to 72 hours postop
time of ambulation
Time frame: up to 48 hours postop
length of Intensive Care Unit stay
Time frame: up to 3 days postop
length of hospital length stay
Time frame: up to 7 days postop
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 2026.
- Individual participant dataSharing planned: No. study results will be shared instead of individual patient data
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ettore Crimi, MD principal investigator
Wake Forest University Health Sciences
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Single dose of methadone, Split dose of methadone and Balanced split dose of methadone in people with Postoperative Pain Management, run by Wake Forest University Health Sciences.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 17 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Plasma methadone concentration (ng/mL) 10 min post initial dose (time frame: 10 minutes). The study lists 12 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Aug 2026.