Ignite Creation Date:
2025-12-26 @ 10:58 AM
Ignite Modification Date:
2025-12-29 @ 2:22 PM
Study NCT ID:
NCT00892606
Status:
COMPLETED
Last Update Posted:
2017-06-14
First Post:
2009-04-30
Is Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Methadone Versus Morphine for Orthopedic Surgery Patients
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D050723', 'term': 'Fractures, Bone'}, {'id': 'D010149', 'term': 'Pain, Postoperative'}], 'ancestors': [{'id': 'D014947', 'term': 'Wounds and Injuries'}, {'id': 'D011183', 'term': 'Postoperative Complications'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D010146', 'term': 'Pain'}, {'id': 'D009461', 'term': 'Neurologic Manifestations'}, {'id': 'D012816', 'term': 'Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D008691', 'term': 'Methadone'}, {'id': 'D009020', 'term': 'Morphine'}, {'id': 'D053610', 'term': 'Opiate Alkaloids'}], 'ancestors': [{'id': 'D007659', 'term': 'Ketones'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D009022', 'term': 'Morphine Derivatives'}, {'id': 'D009019', 'term': 'Morphinans'}, {'id': 'D000470', 'term': 'Alkaloids'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D006572', 'term': 'Heterocyclic Compounds, Bridged-Ring'}, {'id': 'D006576', 'term': 'Heterocyclic Compounds, 4 or More Rings'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}, {'id': 'D010616', 'term': 'Phenanthrenes'}, {'id': 'D011084', 'term': 'Polycyclic Aromatic Hydrocarbons'}, {'id': 'D011083', 'term': 'Polycyclic Compounds'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'nlalsi01@exchange.louisville.edu', 'phone': '502-852-2905', 'title': 'Nancy Alsip', 'organization': 'University Louisville'}, 'certainAgreement': {'piSponsorEmployee': True}}, 'adverseEventsModule': {'eventGroups': [{'id': 'EG000', 'title': 'Methadone', 'description': 'Patients will receive 0.2 mg/kg of methadone IV immediately after intubation\n\nMethadone: Patients will receive 0.2 mg/kg of methadone IV immediately after intubation', 'otherNumAtRisk': 33, 'deathsNumAtRisk': 33, 'otherNumAffected': 0, 'seriousNumAtRisk': 33, 'deathsNumAffected': 0, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Control', 'description': 'Patient will receive current standard-of-care: 0.2 mg/kg of morphine IV immediately after intubation\n\nMorphine: Patients will receive 0.2 mg/kg of morphine IV immediately after intubation', 'otherNumAtRisk': 33, 'deathsNumAtRisk': 33, 'otherNumAffected': 0, 'seriousNumAtRisk': 33, 'deathsNumAffected': 0, 'seriousNumAffected': 0}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Opioid Consumption During the 48 Hours After Surgery', 'denoms': [{'units': 'Participants', 'counts': [{'value': '33', 'groupId': 'OG000'}, {'value': '33', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Methadone', 'description': 'Patients will receive 0.2 mg/kg of methadone IV immediately after intubation\n\nMethadone: Patients will receive 0.2 mg/kg of methadone IV immediately after intubation'}, {'id': 'OG001', 'title': 'Control', 'description': 'Patient will receive current standard-of-care: 0.2 mg/kg of morphine IV immediately after intubation\n\nMorphine: Patients will receive 0.2 mg/kg of morphine IV immediately after intubation'}], 'classes': [{'categories': [{'measurements': [{'value': '51', 'spread': '19', 'groupId': 'OG000'}, {'value': '87', 'spread': '40', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.0072', 'groupIds': ['OG000', 'OG001'], 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'MEAN', 'timeFrame': '48 hours', 'description': 'The amount of opioid required for postoperative pain relief', 'unitOfMeasure': 'mg', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Number of Participants With Post Operative Nausea and Vomiting', 'denoms': [{'units': 'Participants', 'counts': [{'value': '33', 'groupId': 'OG000'}, {'value': '33', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Methadone', 'description': 'Patients will receive 0.2 mg/kg of methadone IV immediately after intubation\n\nMethadone: Patients will receive 0.2 mg/kg of methadone IV immediately after intubation'}, {'id': 'OG001', 'title': 'Control', 'description': 'Patient will receive current standard-of-care: 0.2 mg/kg of morphine IV immediately after intubation\n\nMorphine: Patients will receive 0.2 mg/kg of morphine IV immediately after intubation'}], 'classes': [{'categories': [{'measurements': [{'value': '9', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.004', 'groupIds': ['OG000', 'OG001'], 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': '48 hours', 'description': 'rates subjects experienced PONV', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Visual Pain Score', 'denoms': [{'units': 'Participants', 'counts': [{'value': '33', 'groupId': 'OG000'}, {'value': '33', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Methadone', 'description': 'Patients will receive 0.2 mg/kg of methadone IV immediately after intubation\n\nMethadone: Patients will receive 0.2 mg/kg of methadone IV immediately after intubation'}, {'id': 'OG001', 'title': 'Control', 'description': 'Patient will receive current standard-of-care: 0.2 mg/kg of morphine IV immediately after intubation\n\nMorphine: Patients will receive 0.2 mg/kg of morphine IV immediately after intubation'}], 'classes': [{'categories': [{'measurements': [{'value': '5', 'spread': '3', 'groupId': 'OG000'}, {'value': '6', 'spread': '2', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.0146', 'groupIds': ['OG000', 'OG001'], 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'MEAN', 'timeFrame': '48 hours', 'description': 'Patients rated their pain with the numerical VPS from 0 to 10, with 10 being the worst pain possible and 0 being no pain', 'unitOfMeasure': 'units on a scale', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Methadone', 'description': 'Patients will receive 0.2 mg/kg of methadone IV immediately after intubation\n\nMethadone: Patients will receive 0.2 mg/kg of methadone IV immediately after intubation'}, {'id': 'FG001', 'title': 'Control', 'description': 'Patient will receive current standard-of-care: 0.2 mg/kg of morphine IV immediately after intubation\n\nMorphine: Patients will receive 0.2 mg/kg of morphine IV immediately after intubation'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '38'}, {'groupId': 'FG001', 'numSubjects': '37'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '33'}, {'groupId': 'FG001', 'numSubjects': '33'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '5'}, {'groupId': 'FG001', 'numSubjects': '4'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '38', 'groupId': 'BG000'}, {'value': '37', 'groupId': 'BG001'}, {'value': '75', 'groupId': 'BG002'}]}, {'units': 'participants', 'counts': [{'value': '38', 'groupId': 'BG000'}, {'value': '37', 'groupId': 'BG001'}, {'value': '75', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Methadone', 'description': 'Patients received 2 µg/kg fentanyl, 0.2 mg/kg ketamine, and 0.2 mg/kg of methadone IV immediately after intubation'}, {'id': 'BG001', 'title': 'Control', 'description': 'Patients received 2 µg/kg fentanyl, 0.2 mg/kg ketamine, and 0.2 mg/kg morphine'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '37', 'spread': '13', 'groupId': 'BG000'}, {'value': '35', 'spread': '12', 'groupId': 'BG001'}, {'value': '36', 'spread': '12', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION', 'denomUnitsSelected': 'Participants'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '7', 'groupId': 'BG000'}, {'value': '10', 'groupId': 'BG001'}, {'value': '17', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '31', 'groupId': 'BG000'}, {'value': '27', 'groupId': 'BG001'}, {'value': '58', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants', 'denomUnitsSelected': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United States', 'categories': [{'measurements': [{'value': '38', 'groupId': 'BG000'}, {'value': '37', 'groupId': 'BG001'}, {'value': '75', 'groupId': 'BG002'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants', 'denomUnitsSelected': 'Participants'}], 'typeUnitsAnalyzed': 'participants'}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 75}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2009-01'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2017-05', 'completionDateStruct': {'date': '2013-12', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2017-05-16', 'studyFirstSubmitDate': '2009-04-30', 'resultsFirstSubmitDate': '2017-04-06', 'studyFirstSubmitQcDate': '2009-05-01', 'lastUpdatePostDateStruct': {'date': '2017-06-14', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2017-04-06', 'studyFirstPostDateStruct': {'date': '2009-05-04', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2017-05-17', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2013-12', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Opioid Consumption During the 48 Hours After Surgery', 'timeFrame': '48 hours', 'description': 'The amount of opioid required for postoperative pain relief'}], 'secondaryOutcomes': [{'measure': 'Number of Participants With Post Operative Nausea and Vomiting', 'timeFrame': '48 hours', 'description': 'rates subjects experienced PONV'}, {'measure': 'Visual Pain Score', 'timeFrame': '48 hours', 'description': 'Patients rated their pain with the numerical VPS from 0 to 10, with 10 being the worst pain possible and 0 being no pain'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['Surgery, Orthopedic', 'Pain, Postoperative'], 'conditions': ['Fracture', 'Pain, Postoperative']}, 'referencesModule': {'references': [{'pmid': '11159249', 'type': 'BACKGROUND', 'citation': 'Wadhwa A, Clarke D, Goodchild CS, Young D. Large-dose oral dextromethorphan as an adjunct to patient-controlled analgesia with morphine after knee surgery. Anesth Analg. 2001 Feb;92(2):448-54. doi: 10.1097/00000539-200102000-00032.'}]}, 'descriptionModule': {'briefSummary': 'The investigators propose to compare analgesia by methadone and ketamine with a combination of morphine and ketamine in orthopedic surgery patients with moderate to severe pain. The investigators hypothesize that when given with ketamine before surgical incision, methadone is more effective than morphine in reducing postoperative morphine consumption and reducing pain during movement.', 'detailedDescription': "Patients will receive 1-4 mg midazolam before being transferred to the operating room. All patients will receive standard ASA monitoring. In the operating room, the anesthesiologist will open a randomization envelope to determine patient group assignment (see below). Patients will be anesthetized with 0.2 mg/kg ketamine, 2 µg/kg fentanyl and propofol or etomidate IV. Muscle relaxant of the anesthesiologist's choice will be given and the patient will be intubated. After intubation, the computer-generated randomization codes stored in opaque envelopes will be opened. The patients will be randomized to one of two groups:\n\n1. Methadone group: Patients will receive 0.2 mg/kg of methadone IV immediately after intubation\n2. Control group: Patients will receive 0.2 mg/kg of morphine IV immediately after intubation\n\nThe unblinded investigator will draw the drug and dilute to a total volume of 10 cc. This syringe will be handed to the anesthesia provider, who will administer the medication after induction. They will be maintained with oxygen, air and an inhalational agent of anesthesiologist's choice, targeted at BIS between 40 and 60. Additional analgesia will be provided with fentanyl in 50 µg increments as required throughout surgery. At the end of surgery the neuromuscular block will be reversed and patients will breathe spontaneously. Fentanyl will be titrated to maintain a respiratory rate of 12-15 breaths per minute to obtain an O2 saturation \\> 95% and the other extubation criteria are met before tracheal extubation . The intraoperative use of narcotics, sedatives and anesthetic drugs will be noted. The type of surgery, the duration of surgery and use of additional analgesics and antiemetics will be noted.\n\nAn investigator blinded to randomization will track the patients in the PACU. If rescue medication is necessary, morphine IV will be given in 2-4 mg increments up to a total of 20 mg. If the patients continue to report pain (VAS \\> 4), IV hydromorphone will be given in 0.5 mg dose every 10-15 minutes until the patient has adequate analgesia (VAS \\< 4), as decided by the PACU nurse.\n\nPatients will receive morphine patient-controlled analgesia (PCA) for pain relief as the primary analgesic. Percocet (Acetaminophen/Oxycodone 325 mg/5 mg) or Lortab (Acetaminophen/Hydrocodone 325/5 mg) will be prescribed as needed to maintain VRS \\< 4.\n\nIn the PACU, vital signs including respiratory rate, heart rate, non-invasive blood pressure, sedation score and oxygen saturation will be recorded every 15 minutes. VAS scores for pain will be obtained from the patient every 15 minutes until the patient is discharged to the floor. VAS (visual analog scale) is a 100-mm scale where 0 = no pain and 100 = worst pain imaginable. The investigator will record sedation scores every 15 minutes using the following scale until patient is discharged to the floor:\n\n0-Patient is fully alert\n\n1. Patient has intermittent sedation\n2. Patient sedated but responsive to verbal stimuli\n3. Patient unresponsive to verbal stimuli\n\nPatients will be seen at 8 am and 4 pm on the following day and will be contacted at home or in the hospital on POD 2 and 3 for information regarding pain scores and analgesic requirement. The initial dose of rescue analgesic and time it is given will be recorded. VAS at rest and on movement will be recorded, when the patients are seen or VRS will be recorded via phone contact. Morphine or other analgesics required during the first 24 and 48 hours after surgery, and times to first ambulation, first fluid, solid and flatus will be recorded, as will incidence and severity of postoperative nausea and vomiting be recorded.\n\nOur primary outcome will be opioid consumption during the 48 hours after surgery. All analgesics consumed will be converted to morphine equivalent.\n\nThe secondary outcomes will be\n\n1. Overall rescue analgesic, converted into equipotent doses compared between the two groups\n2. Side effects with special attention paid to respiratory rate and possible respiratory depression, and PONV\n3. Visual pain score at 48 h post-op."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '65 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n* ASA I-III\n* Ages 18-65 years\n* Presenting for lower extremity orthopedic surgery involving fracture of long bones at University of Louisville Hospital\n* Surgery expected to last more than one hour\n* Patient expected to have moderate to severe post-operative pain\n* Patient refused regional anesthesia or has a contraindication to regional anesthesia\n\nExclusion Criteria:\n\n* Any known contraindications to methadone including hypothyroidism, Addison's disease, prostatic hypertrophy, or urethral stricture.\n* Difficulty or inability to understand the study or protocol\n* Known renal or hepatic dysfunction\n* BMI\\> 35\n* Known respiratory or cardiovascular problems, such as obstructive sleep apnea or oxygen saturation of less than 92% on room air\n* Taking any of the known drugs that induce or inhibit the cytochrome p450 enzyme systems. Common examples of these drugs are antifungal, antiretroviral, barbiturates, dexamethasone, and macrolide antibiotics.\n* Pregnancy\n* Taking preoperative opioids for more than 2 weeks before the surgery"}, 'identificationModule': {'nctId': 'NCT00892606', 'briefTitle': 'Methadone Versus Morphine for Orthopedic Surgery Patients', 'organization': {'class': 'OTHER', 'fullName': 'University of Louisville'}, 'officialTitle': 'Effectiveness of Pre-Operative Methadone Versus Morphine for Post-Operative Analgesia in Orthopedic Surgery Patients', 'orgStudyIdInfo': {'id': 'UofL IRB # 08.0200'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Methadone', 'description': 'Patients received 2 µg/kg fentanyl, 0.2 mg/kg ketamine and 0.2 mg/kg of methadone IV with induction of general anesthesia.', 'interventionNames': ['Drug: Methadone']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Control', 'description': 'Patients received 2 µg/kg fentanyl, 0.2 mg/kg ketamine, and 0.2 mg/kg morphine (standard of care)', 'interventionNames': ['Drug: Morphine']}], 'interventions': [{'name': 'Methadone', 'type': 'DRUG', 'otherNames': ['Symoron', 'Dolophine', 'Amidone', 'Methadose', 'Physeptone', 'Heptadon', '6-(Dimethylamino)-4,4-diphenylheptan-3-one (IUPAC name)'], 'description': 'Patients will receive 0.2 mg/kg of methadone IV immediately after intubation', 'armGroupLabels': ['Methadone']}, {'name': 'Morphine', 'type': 'DRUG', 'otherNames': ['Opiate', '(5α,6α)-7,8-didehydro-4,5-epoxy-17-methylmorphinan-3,6-diol'], 'description': 'Patients will receive 0.2 mg/kg of morphine IV immediately after intubation', 'armGroupLabels': ['Control']}]}, 'contactsLocationsModule': {'locations': [{'zip': '40202', 'city': 'Louisville', 'state': 'Kentucky', 'country': 'United States', 'facility': 'University of Louisville Hospital', 'geoPoint': {'lat': 38.25424, 'lon': -85.75941}}], 'overallOfficials': [{'name': 'Anupama Wadhwa, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University of Louisville'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of Louisville', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}