Ignite Creation Date:
2025-12-24 @ 7:43 PM
Ignite Modification Date:
2026-02-21 @ 11:18 PM
Study NCT ID:
NCT06626503
Status:
NOT_YET_RECRUITING
Last Update Posted:
2025-11-19
First Post:
2024-06-15
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Evaluation of Analgesia for Spine Fusion Elective Surgery in Children
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'SINGLE', 'whoMasked': ['PARTICIPANT']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Randomized Clinical Trial'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 500}}, 'statusModule': {'overallStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2026-01-01', 'type': 'ESTIMATED'}, 'statusVerifiedDate': '2025-06', 'completionDateStruct': {'date': '2029-08-31', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-11-15', 'studyFirstSubmitDate': '2024-06-15', 'studyFirstSubmitQcDate': '2024-10-01', 'lastUpdatePostDateStruct': {'date': '2025-11-19', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2024-10-04', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2029-01-31', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Average postoperative pain scores', 'timeFrame': 'Postoperative 48 hours', 'description': 'Average postoperative pain scores at 48-hours timepoint using 0-10, Numerical Rating Scale (NRS), in which 0=no pain at all and 10=worst pain imaginable. Outcome will be reported based on area under the curve (AUC) as mean(SD).'}, {'measure': 'Total postoperative opioid use', 'timeFrame': 'Postoperative 48 hours', 'description': 'Number of opioids used in hospital, will be reported as mean (SD).'}], 'secondaryOutcomes': [{'measure': 'Incidence of inpatient respiratory depression (RD)', 'timeFrame': 'Postoperative 120-hours', 'description': 'RD is defined as persistent oxygen desaturation (SpO2) \\<90% on room air or respiratory rate \\<8 breathes per minute requiring oxygen in the absence of airway obstruction. Outcome will be reported as n(%).'}, {'measure': 'Incidence of Postoperative Nausea and Vomiting (PONV)', 'timeFrame': 'Postoperative 120-hours', 'description': 'PONV will be assess by self-report, EMR, and medication use. Outcome will be reported as n(%).'}, {'measure': 'Incidence of Inpatient Sedation', 'timeFrame': 'Postoperative 120-hours', 'description': 'Sedation will be assessed using the Ramsay Sedation Scale (RSS) and validated sedation scales extracted from the EMR. Outcome will be reported as n(%).'}, {'measure': 'QTc Prolongation', 'timeFrame': 'Postoperative 48-hours', 'description': 'QTc prolongation is defined as more than 460 msec based on 12-lead EKG. Outcome will be reported as n(%).'}, {'measure': 'Length of Hospital Stay (LOS)', 'timeFrame': 'Up to 30 days', 'description': 'LOS will be measured in days until hospital discharge. Outcome will be reported as mean(SD).'}, {'measure': 'Persistent opioid use', 'timeFrame': '1-week, 1-month, and 3-months post-surgery', 'description': 'Based on Prescription Drug Monitoring Program (PDMP) and self-report data. Outcome will be reported as n(%).'}, {'measure': 'Presence of Chronic Postsurgical Pain (CPSP) at 3-months', 'timeFrame': '3-months post-surgery', 'description': 'CPSP incidence will be defined using NRS pain \\>3/10 and functional limitations based on Functional Disability Index (FDI). NRS Pain scale is 0=no pain at all and 10=worst pain imaginable. Outcome will be reported as n(%).'}, {'measure': 'Presence of Opioid Dependence (OD) at 3-months', 'timeFrame': '3-months post-surgery', 'description': 'OD will be assessed using PROMIS and Prescription Pain Medication Misuse (PPMM) scales. Outcome will be reported as n(%).'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Idiopathic Scoliosis']}, 'descriptionModule': {'briefSummary': 'The multicenter PRECISE Analgesia (Prospective Randomized Evaluation of Analgesia for Idiopathic Scoliosis Spine Fusion Elective Surgery in Children) trials will a) implement and investigate the efficacy and safety of multidose methadone-based standardized enhanced recovery after surgery (ERAS) protocol, and b) develop personalized ERAS protocols including precision methadone and oxycodone dosing1,2 and c) personalized analgesia for the safe and effective opioid-sparing management of surgical pain after posterior spine fusion (PSF) in children.', 'detailedDescription': "Specific Aims Aim 1. Conduct a randomized clinical trial in posterior spine fusion (PSF) 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.\n\nAim 2. Develop precision methadone dosing based on age, CYP2B6 and ORM1 variants, and alpha acid glycoprotein (AAG).\n\nAim 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 PSF.\n\nOverall Impact The 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 PSF. 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 adverse events (AEs) in millions of children.\n\nHypothesis 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 PSF. 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, and AAG levels 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."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT'], 'maximumAge': '18 Years', 'minimumAge': '10 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Participants aged 10-\\<18yrs for PSF trial\n* ASA physical status 1\\&2\n* Undergoing PSF for idiopathic scoliosis\n* Participant or legal guardian can speak and read English or Spanish\n\nExclusion Criteria:\n\n* Pregnant patients\n* Methadone allergy\n* Preoperative prolonged QTc more than 460 msec (-30 days to 0 day)\n* 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\\])\n* Preoperative opioid use within 30-days before surgery\n* 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)\n* Significant liver, kidney, neurological disease, developmental delay, or any other co-existing medical condition per discretion of the clinical investigator.'}, 'identificationModule': {'nctId': 'NCT06626503', 'acronym': 'PRECISE', 'briefTitle': 'Evaluation of Analgesia for Spine Fusion Elective Surgery in Children', 'organization': {'class': 'OTHER', 'fullName': 'University of Pittsburgh'}, 'officialTitle': 'Prospective Randomized Evaluation of Analgesia for Spine Fusion Elective Surgery in Children (PRECISE Spine Trial)', 'orgStudyIdInfo': {'id': 'STUDY24040087'}, 'secondaryIdInfos': [{'id': '1U01HD116257-01', 'link': 'https://reporter.nih.gov/quickSearch/1U01HD116257-01', 'type': 'NIH'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Methadone-Based ERAS Group', 'description': '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.', 'interventionNames': ['Drug: Methadone based ERAS']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Non-Methadone-Based Group', 'description': 'The comparator standard-of-care non-methadone-based analgesia arm will include standard opioid analgesia protocol without intra- and post-operative methadone per the current site standards.', 'interventionNames': ['Drug: Non-methadone based group']}], 'interventions': [{'name': 'Methadone based ERAS', 'type': 'DRUG', 'otherNames': ['Methadone Based'], 'description': 'Methadone intervention includes intraoperative intravenous methadone (1st dose: 0.1 mg/kg up to a maximum of 5 mg before incision; 2nd dose: 0.05 mg/kg up to a maximum of 2.5 mg 4 hours after 1st dose) and postoperatively, up to 4 oral doses of methadone every 12 hours before discharge as part of standardized multimodal analgesia in the hospital setting.', 'armGroupLabels': ['Methadone-Based ERAS Group']}, {'name': 'Non-methadone based group', 'type': 'DRUG', 'otherNames': ['Non-methadone'], 'description': 'Non-methadone intervention includes standard opioid analgesia protocol without intra- and post-operative methadone per the current site standards. Postoperative pain medication is recommended when reported pain level is considered moderate or higher (≥4 on NRS and FLACC).', 'armGroupLabels': ['Non-Methadone-Based Group']}]}, 'contactsLocationsModule': {'locations': [{'zip': '15213', 'city': 'Pittsburgh', 'state': 'Pennsylvania', 'country': 'United States', 'contacts': [{'name': 'Senthilkumar Sadhasivam, MD, MPH', 'role': 'CONTACT', 'email': 'sadhasivams@upmc.edu', 'phone': '412-647-4484'}, {'name': 'Amy Monroe, MPH', 'role': 'CONTACT', 'email': 'monroeal@upmc.edu', 'phone': '4126236283'}, {'name': 'Senthilkumar Sadhasivam, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': "UPMC Children's Hospital", 'geoPoint': {'lat': 40.44062, 'lon': -79.99589}}], 'centralContacts': [{'name': 'Amy Monroe, MPH, MBA', 'role': 'CONTACT', 'email': 'monroeal@upmc.edu', 'phone': '412-623-6283'}, {'name': 'Carly Riedmann, MPH', 'role': 'CONTACT', 'email': 'riedmannca@upmc.edu', 'phone': '412-623-4147'}], 'overallOfficials': [{'name': 'Senthilkumar Sadhasivam, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University of Pittsburgh'}]}, 'ipdSharingStatementModule': {'infoTypes': ['STUDY_PROTOCOL', 'SAP'], 'timeFrame': 'Time frame is within 5-years of study completion.', 'ipdSharing': 'YES', 'description': "Identifiable data and specimens will be shared with the sponsor of the study. The investigators and study team will comply with all the NIH's Public Access and Data Sharing requirements including Release of Publications and Sharing of Underlying Primary Data. Release of Publications: The investigators will publish their results in open access journals for broad and free availability immediately without any embargo period. Electronic copies of publications will be deposited within four weeks of acceptance by a journal in PubMed Central with proper metadata to be made discoverable and accessible upon publication.", 'accessCriteria': 'Online collaborative tools to facilitate data sharing such as SharePoint or Xythos'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Senthil Sadhasivam', 'class': 'OTHER'}, 'collaborators': [{'name': 'Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)', 'class': 'NIH'}], 'responsibleParty': {'type': 'SPONSOR_INVESTIGATOR', 'investigatorTitle': 'Professor', 'investigatorFullName': 'Senthil Sadhasivam', 'investigatorAffiliation': 'University of Pittsburgh'}}}}