Evaluation of Analgesia for Cardiac Elective Surgery in Children

NCT ID: NCT06626035

Last Updated: 2025-12-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

500 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-01-31

Study Completion Date

2029-08-31

Brief Summary

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The purpose of this study is to look at a standardized methadone-based enhanced recovery after surgery protocol following pediatric cardiac surgery. This study will consist of randomly assigning children to receive the methadone-based recovery procedures or to receive current standard of care recovery procedures. Randomly assigning means that there is a 50/50 chance, like a coin flip, of being assigned to either research group.

Detailed Description

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Specific Aims Aim 1. Conduct a randomized clinical trial in cardiac surgery (CS) to compare acute pain relief, opioid-sparing efficacy, and safety of standardized perioperative multidose methadone-based enhanced recovery after surgery (ERAS) vs. standard-of-care non-methadone-based analgesia.

Aim 2. Develop precision methadone dosing based on age, CYP2B6 and ORM1 variants, and alpha acid glycoprotein (AAG) levels, cardio-pulmonary bypass (CPB) related dilution.

Aim 3. Identify patient profiles that predict benefits from the assigned analgesia protocol to optimize clinical outcomes. Personalized risk prediction models will be developed and validated including genetic variants (i.e., CYP2B6, CYP2D6, ABCB1, OPRM1, and FAAH), and psychological and clinical factors to predict benefit with the assigned treatments (methadone or non-methadone) for pre-specified clinical endpoints (i.e., lower acute surgical pain, respiratory depression \[RD\], postoperative nausea and vomiting \[PONV\], opioid dependence \[OD\], and chronic postsurgical pain \[CPSP\]) in cardiac surgery.

Overall Impact Investigators will develop actionable evidence for the efficacy of standardized, multidose, methadone-based ERAS protocols and will harness genetic, clinical, and psychological factors contributing to variability in methadone and oxycodone PK, acute surgical pain, transition to CPSP, opioid-induced PONV, RD, and dependence to develop personalized analgesia strategy and dosing for children undergoing cardiac surgery. Implementation of evidence-based standardized methadone-based ERAS pain management and individualized risk prediction will maximize acute surgical pain relief while minimizing opioid use and AEs in millions of children.

Hypothesis The central hypothesis is that a standardized, multidose, methadone-based ERAS protocol will reduce acute surgical pain, overall opioid use, RD, PONV and CPSP compared with standard-of-care short-acting opioid-based analgesia in children undergoing cardiac surgery. The long-term goal is to proactively improve the safety and efficacy of surgical pain control while reducing opioid AEs and the opioid epidemic burden in all children undergoing inpatient surgeries. Further, we hypothesize that age, CYP2B6 and ORM1 variants, AAG levels, and CPB-related dilution will explain methadone's PK variability and dose adjustments that correlate with optimal clinical outcomes, and that patient profiles based on genetic, psychological, and that clinical factors will predict benefits from the assigned analgesia protocol to optimize clinical outcomes.

Conditions

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Pediatric Cardiac Surgery

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Randomized Clinical Trial
Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Participants

Study Groups

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Methadone-Based ERAS Group

The methadone-based standardized analgesia intervention arm will include standardized perioperative care and analgesia, including intraoperative intravenous methadone (1st dose: 0.1 mg/kg up to a maximum of 5 mg before incision; 2nd dose: 0.1 mg/kg up to a maximum of 5 mg 4 hours after 1st dose) and postoperatively, up to 4 oral or IV doses of methadone (0.1 mg/kg up to a maximum of 5 mg) every 12 hours before discharge as part of standardized multimodal analgesia in the hospital setting.

Group Type EXPERIMENTAL

Methadone based ERAS

Intervention Type DRUG

Children randomized to the methadone arm will include standardized perioperative care and analgesia, including intraoperative intravenous methadone (1st dose: 0.1 mg/kg up to a maximum of 5 mg before incision; 2nd dose: 0.1 mg/kg up to a maximum of 5 mg 4 hours after 1st dose) and postoperatively, up to 4 oral or IV doses of methadone (0.1 mg/kg up to a maximum of 5 mg) every 12 hours before discharge as part of standardized multimodal analgesia in the hospital setting.

Non-Methadone-Based Group

Children randomized to the standard-of-care arm will receive standard opioid analgesia protocol without intra- and post-operative methadone per the current site standards.

Group Type ACTIVE_COMPARATOR

Non-methadone based group

Intervention Type DRUG

Children randomized to the standard-of-care arm will receive standard opioid analgesia protocol without intra- and post-operative methadone per the current site standards.

Interventions

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Methadone based ERAS

Children randomized to the methadone arm will include standardized perioperative care and analgesia, including intraoperative intravenous methadone (1st dose: 0.1 mg/kg up to a maximum of 5 mg before incision; 2nd dose: 0.1 mg/kg up to a maximum of 5 mg 4 hours after 1st dose) and postoperatively, up to 4 oral or IV doses of methadone (0.1 mg/kg up to a maximum of 5 mg) every 12 hours before discharge as part of standardized multimodal analgesia in the hospital setting.

Intervention Type DRUG

Non-methadone based group

Children randomized to the standard-of-care arm will receive standard opioid analgesia protocol without intra- and post-operative methadone per the current site standards.

Intervention Type DRUG

Other Intervention Names

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Methadone-Based Standard Care

Eligibility Criteria

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Inclusion Criteria

* Children aged 3-years - \<18 years
* ASA physical status 1, 2, or 3
* Participant or legal guardian can speak and read English or Spanish
* Undergoing the following cardiac surgeries (Categories 1 \& 2) that are associated with significant acute surgical pain

STS Category 1:

* ASD, PFO closure
* VSD repairs,
* Aortic stenosis sub-valvular repair
* ASD and Partial anomalous venous return repair
* AV canal transitional
* Conduit replacement
* Valve replacement (AVR, PVR)
* TOF repair without ventriculostomy

STS Category 2:

* Glenn shunt (on Bypass only)
* Fontan surgery (on Bypass only)
* Pulmonary artery plasty (main)
* Left Atrium (LA) to Pulmonary Artery (PA) conduit replacement.

Exclusion Criteria

* Pregnant patients
* Methadone allergy
* Preoperative prolonged QTc more than 460 msec (-30 days to 0 day)
* Subjects undergoing concomitant treatment with known cytochrome P450 inhibitors included in methadone labeling (i.e. macrolides (e.g. erythromycin), azole-antifungal agents (e.g. ketoconazole, voriconazole), protease inhibitors (e.g. ritonavir), fluconazole, SSRIs (e.g. sertraline, fluvoxamine)
* Preoperative opioid use within 30 days before surgery
* History of severe sleep apnea (have a sleep study with an AHI index score more than 10 or clinical signs of sleep disordered breathing - snoring, daytime drowsiness)
* Significant liver, kidney, neurological disease, developmental delay, or any other co-existing medical condition per discretion of the clinical investigator
Minimum Eligible Age

3 Years

Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role collaborator

Senthil Sadhasivam

OTHER

Sponsor Role lead

Responsible Party

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Senthil Sadhasivam

Professor

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Senthilkumar Sadhasivam, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

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UPMC Children's Hospital

Pittsburgh, Pennsylvania, United States

Site Status

Countries

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United States

Central Contacts

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Amy Monroe, MPH, MBA

Role: CONTACT

Phone: 412-623-6283

Email: [email protected]

Carly Riedmann, MPH

Role: CONTACT

Phone: 412-623-4147

Email: [email protected]

Facility Contacts

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Senthilkumar Sadhasivam, MD, MPH

Role: primary

Amy Monroe, MPH

Role: backup

Other Identifiers

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U01HD116257

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STUDY24040108

Identifier Type: -

Identifier Source: org_study_id