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Patient will receive lamotrigine vs. placebo with small sips of water. Lamotrigine reaches peak level 1-4 hours after oral administration.
1:1 randomization without stratification use web-based software (Redcap) before surgery. Allocation will be concealed from the patient, the nurse, the operating room team. Both patient and the operating room team will be blinded to the treatment allocation (double blind).
Standard preoperative care as per anesthesia care team. Patient will receive lamotrigine vs. placebo with small sips of water. Lamotrigine reaches peak level 1-4 hours after oral administration. Single dose lamotrigine is safe and is not associated with rash.
Standard intraoperative care as per the anesthesia care team. All patients will receive Ketamine 1 mg/kg at induction. Ketamine 5mcg/kg/min will be started at induction and stopped at the end of surgery.
Standard postoperative care as per PACU team. The psychologic side-effects will be measured using Brief Psychiatric Rating Scale (BPRS) using an online tool.
Research fellow will receive standardized training in administering BPRS from Dr. Amit Anand using structured material. Dr. Anand has used this training for other current research projects.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| lamotrigine | Active Comparator | Patient will receive 300 mg of oral lamotrigine with small sips of water to reduce the psychologic side effects (measured by four key items of Brief Psychiatric Rating Scale: conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content) of intraoperative ketamine use. |
|
| Placebo | Placebo Comparator | Patient will receive oral Placebo with small sips of water, to reduce the psychologic side effects (measured by four key items of Brief Psychiatric Rating Scale: conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content) of intraoperative ketamine use. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lamotrigine 300 MG | Drug | 300 mg of oral Lamotrigine. One of the key studies in this area was reported at the Society of Neuroscience meeting in 1997 and later published in the Archives of General Psychiatry. This study reported that, in healthy subjects 300 mg oral lamotrigine significantly decreased ketamine-induced perceptual abnormalities as assessed by the Clinician-Administered Dissociative States Scale (P<.001).31 Furthermore lamotrigine increased the immediate mood-elevating effects of ketamine (P<.05). |
| Measure | Description | Time Frame |
|---|---|---|
| Psychologic Side-effects | The primary outcome of psychologic side-effects was measured in PACU (up to 90 minutes after ketamine infusion). This included four key items of the Brief Psychiatric Rating Scale (BPRS) corresponding to positive symptoms of schizophrenia: conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content. Each symptom is rated 1-7 ( 1 = not present, 2 = very mild, 3 = mild, 4 = moderate, 5 = moderately severe, 6 = severe, 7 = extremely severe ), and, therefore, the total score as the primary outcome based on four key items of BPRS will be between 4 (best score) and 28 (worst score). | in PACU (up to 90 minutes after ketamine infusion) |
| Number of Patients With Psychologic Disturbances- | The psychologic side-effects were measured in PACU (up to 90 minutes after ketamine infusion). This included four key items of the Brief Psychiatric Rating Scale (BPRS) corresponding to positive symptoms of schizophrenia: conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content. Each symptom is rated 1-7 ( 1 = not present, 2 = very mild, 3 = mild, 4 = moderate, 5 = moderately severe, 6 = severe, 7 = extremely severe ), and, therefore, the total score as the primary outcome based on four key items of BPRS will be between 4 (best score) and 28 (worst score). Patients who had a total score of 4 (all symptoms not present) were determined as not having psychologic disturbance and patients who had a total score of > 4 (having any symptoms present) were determined as having psychologic disturbance. | Up to 90 minutes of PACU arrival |
| Measure | Description | Time Frame |
|---|---|---|
| Total Opioid Consumption in PACU (mg) | Total cumulative opioid use (total IV morphine equivalents) in postoperative anesthesia care unit (PACU) | from entry to PACU to leaving PACU, up to 4 hours |
| Pain Score in PACU |
| Measure | Description | Time Frame |
|---|---|---|
| Daily Average Opioid Use During Hospital Stay | The average daily opioid use (mg) during the hospital stay. | from admission up to discharge |
| Opioid Related Side-effects (ORSDS)-POD1 | ORSDS is a 4 point-scale that evaluates 3 symptom distress dimensions (frequency, severity, bothersomeness for 12 opioid-related side effects, with a score of each item ranging from 0 to 4 where higher scores mean more side effects). The final ORSDS score is the average of all 12 scores from those 12 items, ranging from 0 to 4 where a higher score means worse outcome. This one measure ORSDS at postoperative day 1 |
Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cleveland Clinic | Cleveland | Ohio | 44195 | United States |
There is no plan to make subjects data available to outside researchers
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| ID | Title | Description |
|---|---|---|
| FG000 | Lamotrigine | Preoperatively, the patient will receive 300 mg of oral lamotrigine pill with small sips of water once. |
| FG001 | Placebo | Preoperatively, the patient will receive a 300 mg oral placebo pill with small sips of water once. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Lamotrigine | Preoperatively, the patient will receive 300 mg of oral lamotrigine pill with small sips of water once. |
| BG001 | Placebo | Preoperatively, the patient will receive a 300 mg oral placebo pill with small sips of water once. |
| 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 | Psychologic Side-effects | The primary outcome of psychologic side-effects was measured in PACU (up to 90 minutes after ketamine infusion). This included four key items of the Brief Psychiatric Rating Scale (BPRS) corresponding to positive symptoms of schizophrenia: conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content. Each symptom is rated 1-7 ( 1 = not present, 2 = very mild, 3 = mild, 4 = moderate, 5 = moderately severe, 6 = severe, 7 = extremely severe ), and, therefore, the total score as the primary outcome based on four key items of BPRS will be between 4 (best score) and 28 (worst score). | 46 patients were analyzed but 3 people were missing on the primary outcome. | Posted | Median | Inter-Quartile Range | score on a scale | in PACU (up to 90 minutes after ketamine infusion) |
|
from the beginning of the study to discharge, up to 10 days.
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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 | Lamotrigine | Patient will receive 300 mg of oral lamotrigine with small sips of water to reduce the psychologic side effects (measured by four key items of Brief Psychiatric Rating Scale: conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content) of intraoperative ketamine use. Lamotrigine 300 MG: 300 mg of oral Lamotrigine. One of the key studies in this area was reported at the Society of Neuroscience meeting in 1997 and later published in the Archives of General Psychiatry. This study reported that, in healthy subjects 300 mg oral lamotrigine significantly decreased ketamine-induced perceptual abnormalities as assessed by the Clinician-Administered Dissociative States Scale (P<.001).31 Furthermore lamotrigine increased the immediate mood-elevating effects of ketamine (P<.05). Ketamine: 1mg/kg bolus at induction followed by 5 microgram/kg/min infusion till the end of the surgery |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr Kamal Maheshwari | Cleveland Clinic | 216-318-7235 | maheshk@ccf.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 7, 2019 | Mar 11, 2021 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D000077213 | Lamotrigine |
| D007649 | Ketamine |
| ID | Term |
|---|---|
| D014227 | Triazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D003510 | Cyclohexanes |
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randomization without stratification
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The Pharmacy will know the treatment
|
|
| Placebo | Drug | 300 mg of oral Placebo |
|
| Ketamine | Drug | 1mg/kg bolus at induction followed by 5 microgram/kg/min infusion till the end of the surgery |
|
Pain score was scaled from 0-10 where 0 means no pain and 10 means most pain. The time-weighted average of pain scores was used if the pain score was measured multiple times.
| from entry to PACU to leaving PACU |
| Number of Patients Who Had PONV (Postoperative Nausea Vomiting) | PONV was measured through Postoperative Nursing Progress Record, where nausea vomiting severity was recorded as 0 (none), 1 (mild), 2 (moderate), 3 (severe). Patients whose score was 0 were determined as not having PONV and patients whose score was positive were determined as having PONV. | after surgery up to discharge |
| postoperative day 1 |
| Opioid Related Side-effects (ORSDS)-POD2 | ORSDS is a 4 point-scale that evaluates 3 symptom distress dimensions (frequency, severity, bothersomeness for 12 opioid-related side effects, with a score of each item ranging from 0 to 4 where higher scores mean more side effects). The final ORSDS score is the average of all 12 scores from those 12 items, ranging from 0 to 4 where a higher score means a worse outcome. This one measure ORSDS at postoperative day 2. | postoperative day 2 |
| PACU Length of Stay, Hours | Hours spent in PACU (Postanesthesia Care Unit). | in PACU |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| ASA status, No (%) | The ASA Physical Status Classification System is to assess and communicate a patient's pre-anesthesia medical co-morbidities. ASA scores included I, II, III, IV, V, and VI where I means normal status (best) and VI means a declared brain-dead patient whose organs are being removed for donor purposes (worst). | Count of Participants | Participants |
|
| History of alcoholism | Count of Participants | Participants |
|
| Surgery duration (hours) | Median | Inter-Quartile Range | hours |
|
| Surgery type | Count of Participants | Participants |
|
| Hypertension | Count of Participants | Participants |
|
| Chronic pulmonary disease | Count of Participants | Participants |
|
| Diabetes | Count of Participants | Participants |
|
| Renal failure | Count of Participants | Participants |
|
| Psychoses | Count of Participants | Participants |
|
| Depression | Count of Participants | Participants |
|
| Other neurological disorders | Count of Participants | Participants |
|
| BPRS(Brief Psychiatric Rating Scale) baseline score | Brief Psychiatric Rating Scale (BPRS) corresponding to positive symptoms of schizophrenia: conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content. Each symptom is rated 1-7 ( 1 = not present, 2 = very mild, 3 = mild, 4 = moderate, 5 = moderately severe, 6 = severe, 7 = extremely severe ), and, therefore, the total score based on four key items of BPRS will be between 4 (best score) and 28 (worst score). | Median | Inter-Quartile Range | scores |
|
| Positive symptoms of schizophrenia based on four key items of BPRS (Brief Psychiatric Rati)-baseline | Count of Participants | Participants |
|
| Total dose of Ketamine, mg | Mean | Standard Deviation | mg |
|
| OG001 | Placebo | Preoperatively, the patient will receive a 300 mg oral placebo pill with small sips of water once. |
|
|
|
| Primary | Number of Patients With Psychologic Disturbances- | The psychologic side-effects were measured in PACU (up to 90 minutes after ketamine infusion). This included four key items of the Brief Psychiatric Rating Scale (BPRS) corresponding to positive symptoms of schizophrenia: conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content. Each symptom is rated 1-7 ( 1 = not present, 2 = very mild, 3 = mild, 4 = moderate, 5 = moderately severe, 6 = severe, 7 = extremely severe ), and, therefore, the total score as the primary outcome based on four key items of BPRS will be between 4 (best score) and 28 (worst score). Patients who had a total score of 4 (all symptoms not present) were determined as not having psychologic disturbance and patients who had a total score of > 4 (having any symptoms present) were determined as having psychologic disturbance. | A total of 3 people were missing on this outcome | Posted | Count of Participants | Participants | Up to 90 minutes of PACU arrival |
|
|
|
|
| Secondary | Total Opioid Consumption in PACU (mg) | Total cumulative opioid use (total IV morphine equivalents) in postoperative anesthesia care unit (PACU) | The final study population. | Posted | Median | Inter-Quartile Range | mg | from entry to PACU to leaving PACU, up to 4 hours |
|
|
|
|
| Secondary | Pain Score in PACU | Pain score was scaled from 0-10 where 0 means no pain and 10 means most pain. The time-weighted average of pain scores was used if the pain score was measured multiple times. | The final study population | Posted | Mean | Standard Deviation | score on a scale | from entry to PACU to leaving PACU |
|
|
|
|
| Secondary | Number of Patients Who Had PONV (Postoperative Nausea Vomiting) | PONV was measured through Postoperative Nursing Progress Record, where nausea vomiting severity was recorded as 0 (none), 1 (mild), 2 (moderate), 3 (severe). Patients whose score was 0 were determined as not having PONV and patients whose score was positive were determined as having PONV. | Two patients were missing on this outcome. | Posted | Count of Participants | Participants | after surgery up to discharge |
|
|
|
|
| Other Pre-specified | Daily Average Opioid Use During Hospital Stay | The average daily opioid use (mg) during the hospital stay. | The final study population. | Posted | Median | Inter-Quartile Range | mg | from admission up to discharge |
|
|
|
| Other Pre-specified | Opioid Related Side-effects (ORSDS)-POD1 | ORSDS is a 4 point-scale that evaluates 3 symptom distress dimensions (frequency, severity, bothersomeness for 12 opioid-related side effects, with a score of each item ranging from 0 to 4 where higher scores mean more side effects). The final ORSDS score is the average of all 12 scores from those 12 items, ranging from 0 to 4 where a higher score means worse outcome. This one measure ORSDS at postoperative day 1 | The final study population. | Posted | Median | Inter-Quartile Range | score on a scale | postoperative day 1 |
|
|
|
| Other Pre-specified | Opioid Related Side-effects (ORSDS)-POD2 | ORSDS is a 4 point-scale that evaluates 3 symptom distress dimensions (frequency, severity, bothersomeness for 12 opioid-related side effects, with a score of each item ranging from 0 to 4 where higher scores mean more side effects). The final ORSDS score is the average of all 12 scores from those 12 items, ranging from 0 to 4 where a higher score means a worse outcome. This one measure ORSDS at postoperative day 2. | the final study population. | Posted | Median | Inter-Quartile Range | score on a scale | postoperative day 2 |
|
|
|
| Other Pre-specified | PACU Length of Stay, Hours | Hours spent in PACU (Postanesthesia Care Unit). | the final study population | Posted | Median | Inter-Quartile Range | hours | in PACU |
|
|
|
| 0 |
| 23 |
| 0 |
| 23 |
| 0 |
| 23 |
| EG001 | Placebo | Patient will receive oral Placebo with small sips of water, to reduce the psychologic side effects (measured by four key items of Brief Psychiatric Rating Scale: conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content) of intraoperative ketamine use. Placebo: 300 mg of oral Placebo Ketamine: 1mg/kg bolus at induction followed by 5 microgram/kg/min infusion till the end of the surgery | 0 | 23 | 0 | 23 | 0 | 23 |
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| D003516 |
| Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |