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Scoliosis is a disease that involves lateral and/or rotational deformity of the spine and can affect up to 4% of the population. Typically, surgery is considered when Cobb's angle, which is a measurement used for evaluation of curves in scoliosis on an anterior-posterior radiographic projection of the spine, is greater than 50 degrees in the thoracic region (40 degrees in the lumbar region) or when the curvature causes significant pain, or respiratory and cardiovascular restriction. Patient undergoing this surgical correction experience severe pain in the postoperative period and the management includes the use of opioid-based patient-controlled analgesia (PCA).
Scoliosis is a disease that involves lateral and/or rotational deformity of the spine and can affect up to 4% of the population. Typically, surgery is considered when Cobb's angle, which is a measurement used for evaluation of curves in scoliosis on an anterior-posterior radiographic projection of the spine, is greater than 50 degrees in the thoracic region (40 degrees in the lumbar region) or when the curvature causes significant pain, or respiratory and cardiovascular restriction. Patient undergoing this surgical correction experience severe pain in the postoperative period and the management includes the use of opioid-based patient-controlled analgesia (PCA).
Methadone is an opioid with one of the longest elimination half-life and has been used as an effective analgesic for acute, chronic, neuropathic, and cancer pain in adults, children, and even neonates1-5. Its long duration of action and antagonism to the N-methyl-d-aspartate receptor may decrease the need for PCA use in the postoperative period. Gourlay2 demonstrated the effectiveness and utility of perioperative methadone including the advantages of longer analgesia with no serious side effects of respiratory depression. A recent study by Gottschalk2 in adult patients demonstrated a 50% reduction of postoperative opioids at 48 hours and lower pain scores after a single bolus of methadone before surgical incision. However, a major weakness of the study is that patients did not receive equipotent intraoperative opioids. In addition, the adolescent patient population will undergo a much larger surgical incision with potential for greater postoperative pain. Despite this potential benefit, methadone is seldom used in the perioperative setting. A more recent pharmacokinetic study of methadone in adolescents undergoing spine surgery failed to show a reduction in opioid consumption as it was powered to determine pharmacokinetics and not a secondary endpoint of postoperative opioid consumption. An appropriately powered study is still required to determine the efficacy of methadone in reducing postoperative pain after spine surgery.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment group | Active Comparator | The treatment group will receive 0.2 mg/kg methadone diluted to a 20 ml infusion over 10 minutes. |
|
| Control Group | Placebo Comparator | The control group will receive a 20 ml normal saline placebo infusion over 10 minutes |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Methadone | Drug | The treatment group will receive 0.2 mg/kg methadone diluted to a 20 ml infusion over 10 minutes |
|
| Measure | Description | Time Frame |
|---|---|---|
| Opioid Usage | Subjects were given access to Patient-Controlled Intravenous Opioid Administration (PCA) to manage their post-operative pain. The doses of morphine were calculated at at PACU, 24 hours, 48 hours and 72 hours respectively. | Admission to PACU to 72 hours post-operative |
| Measure | Description | Time Frame |
|---|---|---|
| Pain Scores | The FLACC scale or Face, Legs, Activity, Cry, Consolability scale is a measurement used to assess pain for children between the ages of 2 months and 7 years or individuals that are unable to communicate their pain. The scale is scored in a range of 0-10 with 0 representing no pain. The scale has five criteria, which are each assigned a score of 0, 1 or 2. The data reported here represents the mean difference in FLACC score by treatment group at PACU, 24 hours, 48 hours and 72 hours, respectively. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Kim Nguyen, MD | Baylor College of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Texas Children's Hospital | Houston | Texas | 77030 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 17943808 | Background | Nicholson AB. Methadone for cancer pain. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD003971. doi: 10.1002/14651858.CD003971.pub3. | |
| 6128949 | Background | Gourlay GK, Wilson PR, Glynn CJ. Pharmacodynamics and pharmacokinetics of methadone during the perioperative period. Anesthesiology. 1982 Dec;57(6):458-67. doi: 10.1097/00000542-198212000-00005. No abstract available. |
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Methods of statistical analysis may be shared at study completion.
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| ID | Title | Description |
|---|---|---|
| FG000 | Treatment Group | The treatment group will receive 0.2 mg/kg methadone diluted to a 20 ml infusion over 10 minutes. Methadone: The treatment group will receive 0.2 mg/kg methadone diluted to a 20 ml infusion over 10 minutes |
| FG001 | Control Group | The control group will receive a 20 ml normal saline placebo infusion over 10 minutes Normal Saline: the control group will receive a 20 ml normal saline placebo infusion over 10 minutes |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Treatment Group | The treatment group will receive 0.2 mg/kg methadone diluted to a 20 ml infusion over 10 minutes. Methadone: The treatment group will receive 0.2 mg/kg methadone diluted to a 20 ml infusion over 10 minutes |
| BG001 | Control Group |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Opioid Usage | Subjects were given access to Patient-Controlled Intravenous Opioid Administration (PCA) to manage their post-operative pain. The doses of morphine were calculated at at PACU, 24 hours, 48 hours and 72 hours respectively. | Posted | Median | Inter-Quartile Range | mg/kg | Admission to PACU to 72 hours post-operative |
|
At any time during hospitalization (Days 0 to 5)
Side effects of Methadone versus Placebo group were assessed during the duration of the subject's hospitalization. Incidents were counted once per subject.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Treatment Group | The treatment group will receive 0.2 mg/kg methadone diluted to a 20 ml infusion over 10 minutes. Methadone: The treatment group will receive 0.2 mg/kg methadone diluted to a 20 ml infusion over 10 minutes |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea and Vomiting | Gastrointestinal disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Kim P. Nguyen, MD, Principal Investigator | Baylor College of Medicine | 832-824-5907 | kpnguyen@texaschildrens.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 28, 2020 | Dec 28, 2020 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D008691 | Methadone |
| D000077330 | Saline Solution |
| D035061 | Control Groups |
| ID | Term |
|---|---|
| D007659 | Ketones |
| D009930 | Organic Chemicals |
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
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| Normal Saline | Drug | the control group will receive a 20 ml normal saline placebo infusion over 10 minutes |
|
|
| Admission to PACU to 72 hours post-operative |
| 20418538 | Background | Gottschalk A, Durieux ME, Nemergut EC. Intraoperative methadone improves postoperative pain control in patients undergoing complex spine surgery. Anesth Analg. 2011 Jan;112(1):218-23. doi: 10.1213/ANE.0b013e3181d8a095. Epub 2010 Apr 24. |
| 22037641 | Background | Sharma A, Tallchief D, Blood J, Kim T, London A, Kharasch ED. Perioperative pharmacokinetics of methadone in adolescents. Anesthesiology. 2011 Dec;115(6):1153-61. doi: 10.1097/ALN.0b013e318238fec5. |
| 2066846 | Background | Berde CB, Beyer JE, Bournaki MC, Levin CR, Sethna NF. Comparison of morphine and methadone for prevention of postoperative pain in 3- to 7-year-old children. J Pediatr. 1991 Jul;119(1 Pt 1):136-41. doi: 10.1016/s0022-3476(05)81054-6. |
| Protocol Violation |
|
The control group will receive a 20 ml normal saline placebo infusion over 10 minutes Normal Saline: the control group will receive a 20 ml normal saline placebo infusion over 10 minutes |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Weight | Mean | Standard Deviation | kg |
|
| Height | Mean | Standard Deviation | cm |
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| Body Mass Index | Mean | Standard Deviation | kg/m^2 |
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| ASA Status | The ASA (American Society of Anesthesiologists) physical status classification system is a system for assessing the fitness of patients before surgery. ASA I: A normal healthy patient ASA II: A patient with mild systemic disease ASA III: A patient with severe systemic disease | Count of Participants | Participants |
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| Secondary | Pain Scores | The FLACC scale or Face, Legs, Activity, Cry, Consolability scale is a measurement used to assess pain for children between the ages of 2 months and 7 years or individuals that are unable to communicate their pain. The scale is scored in a range of 0-10 with 0 representing no pain. The scale has five criteria, which are each assigned a score of 0, 1 or 2. The data reported here represents the mean difference in FLACC score by treatment group at PACU, 24 hours, 48 hours and 72 hours, respectively. | Posted | Mean | Standard Deviation | units on a scale | Admission to PACU to 72 hours post-operative |
|
|
|
| 0 |
| 32 |
| 0 |
| 32 |
| 15 |
| 32 |
| EG001 | Control Group | The control group will receive a 20 ml normal saline placebo infusion over 10 minutes Normal Saline: the control group will receive a 20 ml normal saline placebo infusion over 10 minutes | 0 | 30 | 0 | 30 | 14 | 30 |
| Constipation | Gastrointestinal disorders | Systematic Assessment |
|
| Hypoxemia (oxygen required) | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| D012996 |
| Solutions |
| D004364 | Pharmaceutical Preparations |
| D015340 | Epidemiologic Research Design |
| D004812 | Epidemiologic Methods |
| D008919 | Investigative Techniques |
| D012107 | Research Design |
| D008722 | Methods |
| III |
|
| 48 Hours |
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| 72 Hours |
|