Trial Outcomes & Findings for Lamotrigine in Reducing Psychologic Side-Effect of Perioperative Ketamine (NCT NCT03831854)

Last Updated: 2021-06-09

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

46 participants

Primary outcome timeframe

in PACU (up to 90 minutes after ketamine infusion)

Results posted on

2021-06-09

Participant Flow

Participant milestones

Participant milestones
Measure	Lamotrigine Preoperatively, the patient will receive 300 mg of oral lamotrigine pill with small sips of water once.	Placebo Preoperatively, the patient will receive a 300 mg oral placebo pill with small sips of water once.
Overall Study STARTED	23	23
Overall Study COMPLETED	23	23
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Lamotrigine in Reducing Psychologic Side-Effect of Perioperative Ketamine

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lamotrigine n=23 Participants Preoperatively, the patient will receive 300 mg of oral lamotrigine pill with small sips of water once.	Placebo n=23 Participants Preoperatively, the patient will receive a 300 mg oral placebo pill with small sips of water once.	Total n=46 Participants Total of all reporting groups
Age, Continuous	44 years STANDARD_DEVIATION 13 • n=5 Participants	42 years STANDARD_DEVIATION 12 • n=7 Participants	43 years STANDARD_DEVIATION 12 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	14 Participants n=7 Participants	25 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	9 Participants n=7 Participants	21 Participants n=5 Participants
Race/Ethnicity, Customized White	20 Participants n=5 Participants	19 Participants n=7 Participants	39 Participants n=5 Participants
Race/Ethnicity, Customized Other	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
ASA status, No (%) I	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
ASA status, No (%) II	9 Participants n=5 Participants	12 Participants n=7 Participants	21 Participants n=5 Participants
ASA status, No (%) III	13 Participants n=5 Participants	11 Participants n=7 Participants	24 Participants n=5 Participants
History of alcoholism	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Surgery duration (hours)	4 hours n=5 Participants	3 hours n=7 Participants	3.5 hours n=5 Participants
Surgery type Orthopedic	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Surgery type Abdominal	20 Participants n=5 Participants	17 Participants n=7 Participants	37 Participants n=5 Participants
Surgery type General	1 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants
Hypertension	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Chronic pulmonary disease	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Diabetes	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Renal failure	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Psychoses	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Depression	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Other neurological disorders	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
BPRS(Brief Psychiatric Rating Scale) baseline score	25 scores n=5 Participants	25 scores n=7 Participants	25 scores n=5 Participants
Positive symptoms of schizophrenia based on four key items of BPRS (Brief Psychiatric Rati)-baseline	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Total dose of Ketamine, mg	143 mg STANDARD_DEVIATION 48 • n=5 Participants	142 mg STANDARD_DEVIATION 54 • n=7 Participants	143 mg STANDARD_DEVIATION 51 • n=5 Participants

PRIMARY outcome

Timeframe: in PACU (up to 90 minutes after ketamine infusion)

Population: 46 patients were analyzed but 3 people were missing on the primary outcome.

Outcome measures

Outcome measures
Measure	Lamotrigine n=22 Participants Preoperatively, the patient will receive 300 mg of oral lamotrigine pill with small sips of water once.	Placebo n=21 Participants Preoperatively, the patient will receive a 300 mg oral placebo pill with small sips of water once.
Psychologic Side-effects	4 score on a scale Interval 4.0 to 4.0	4 score on a scale Interval 4.0 to 4.0

PRIMARY outcome

Timeframe: Up to 90 minutes of PACU arrival

Population: A total of 3 people were missing on this outcome

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.

Outcome measures

Outcome measures
Measure	Lamotrigine n=22 Participants Preoperatively, the patient will receive 300 mg of oral lamotrigine pill with small sips of water once.	Placebo n=21 Participants Preoperatively, the patient will receive a 300 mg oral placebo pill with small sips of water once.
Number of Patients With Psychologic Disturbances-	0 Participants	3 Participants

SECONDARY outcome

Timeframe: from entry to PACU to leaving PACU, up to 4 hours

Population: The final study population.

Total cumulative opioid use (total IV morphine equivalents) in postoperative anesthesia care unit (PACU)

Outcome measures

Outcome measures
Measure	Lamotrigine n=23 Participants Preoperatively, the patient will receive 300 mg of oral lamotrigine pill with small sips of water once.	Placebo n=23 Participants Preoperatively, the patient will receive a 300 mg oral placebo pill with small sips of water once.
Total Opioid Consumption in PACU (mg)	5 mg Interval 0.0 to 15.0	10 mg Interval 0.0 to 15.0

SECONDARY outcome

Timeframe: from entry to PACU to leaving PACU

Population: The final study population

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.

Outcome measures

Outcome measures
Measure	Lamotrigine n=23 Participants Preoperatively, the patient will receive 300 mg of oral lamotrigine pill with small sips of water once.	Placebo n=23 Participants Preoperatively, the patient will receive a 300 mg oral placebo pill with small sips of water once.
Pain Score in PACU	4.9 score on a scale Standard Deviation 3.1	4.4 score on a scale Standard Deviation 2.8

SECONDARY outcome

Timeframe: after surgery up to discharge

Population: Two patients were missing on this outcome.

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.

Outcome measures

Outcome measures
Measure	Lamotrigine n=22 Participants Preoperatively, the patient will receive 300 mg of oral lamotrigine pill with small sips of water once.	Placebo n=22 Participants Preoperatively, the patient will receive a 300 mg oral placebo pill with small sips of water once.
Number of Patients Who Had PONV (Postoperative Nausea Vomiting)	5 Participants	5 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: from admission up to discharge

Population: The final study population.

The average daily opioid use (mg) during the hospital stay.

Outcome measures

Outcome measures
Measure	Lamotrigine n=23 Participants Preoperatively, the patient will receive 300 mg of oral lamotrigine pill with small sips of water once.	Placebo n=23 Participants Preoperatively, the patient will receive a 300 mg oral placebo pill with small sips of water once.
Daily Average Opioid Use During Hospital Stay	24 mg Interval 15.0 to 69.0	24 mg Interval 15.0 to 58.0

OTHER_PRE_SPECIFIED outcome

Timeframe: postoperative day 1

Population: The final study population.

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

Outcome measures

Outcome measures
Measure	Lamotrigine n=23 Participants Preoperatively, the patient will receive 300 mg of oral lamotrigine pill with small sips of water once.	Placebo n=23 Participants Preoperatively, the patient will receive a 300 mg oral placebo pill with small sips of water once.
Opioid Related Side-effects (ORSDS)-POD1	0.38 score on a scale Interval 0.0 to 0.58	0.57 score on a scale Interval 0.0 to 0.74

OTHER_PRE_SPECIFIED outcome

Timeframe: postoperative day 2

Population: the final study population.

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.

Outcome measures

Outcome measures
Measure	Lamotrigine n=23 Participants Preoperatively, the patient will receive 300 mg of oral lamotrigine pill with small sips of water once.	Placebo n=23 Participants Preoperatively, the patient will receive a 300 mg oral placebo pill with small sips of water once.
Opioid Related Side-effects (ORSDS)-POD2	0.18 score on a scale Interval 0.0 to 3.5	0.26 score on a scale Interval 0.16 to 0.67

OTHER_PRE_SPECIFIED outcome

Timeframe: in PACU

Population: the final study population

Hours spent in PACU (Postanesthesia Care Unit).

Outcome measures

Outcome measures
Measure	Lamotrigine n=23 Participants Preoperatively, the patient will receive 300 mg of oral lamotrigine pill with small sips of water once.	Placebo n=23 Participants Preoperatively, the patient will receive a 300 mg oral placebo pill with small sips of water once.
PACU Length of Stay, Hours	1 hours Interval 1.0 to 1.0	2 hours Interval 1.0 to 2.0

Adverse Events

Lamotrigine

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr Kamal Maheshwari

Cleveland Clinic

Phone: 216-318-7235

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place