Trial Outcomes & Findings for The Efficacy of Intravenous Acetaminophen During Perioperative Neurosurgery Period (NCT NCT01739699)

NCT ID: NCT01739699

Last Updated: 2021-11-04

Results Overview

The purpose of the study was to determine whether more patients undergoing craniotomies would not require any opioids (i.e., opioid consumption reduced to zero) during the first 24 postoperative hours when receiving intravenous (IV) acetaminophen during that time compared to those receiving placebo (normal saline).

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 140 participants
• Primary outcome timeframe: during first 24 hours after surgery
• Results posted on: 2021-11-04

Participant Flow

Participant milestones

Measure	Acetaminophen Subjects will receive 1000mg of intravenous acetaminophen every 6 hours for 24 hours beginning with dural closure. Acetaminophen	Placebo Subjects will receive 100cc of normal saline every 6 hours for 24 hours beginning at dural closure. Placebo
Overall Study STARTED	70	70
Overall Study COMPLETED	66	65
Overall Study NOT COMPLETED	4	5

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Acetaminophen n=70 Participants Subjects will receive 1000mg of intravenous acetaminophen every 6 hours for 24 hours beginning with dural closure. Acetaminophen	Placebo n=70 Participants Subjects will receive 100cc of normal saline every 6 hours for 24 hours beginning at dural closure. Placebo	Total n=140 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=70 Participants	0 Participants n=70 Participants	0 Participants n=140 Participants
Age, Categorical Between 18 and 65 years	46 Participants n=70 Participants	45 Participants n=70 Participants	91 Participants n=140 Participants
Age, Categorical >=65 years	24 Participants n=70 Participants	25 Participants n=70 Participants	49 Participants n=140 Participants
Age, Continuous	58 years STANDARD_DEVIATION 15 • n=70 Participants	56 years STANDARD_DEVIATION 13 • n=70 Participants	57 years STANDARD_DEVIATION 14 • n=140 Participants
Sex: Female, Male Female	41 Participants n=70 Participants	36 Participants n=70 Participants	77 Participants n=140 Participants
Sex: Female, Male Male	29 Participants n=70 Participants	34 Participants n=70 Participants	63 Participants n=140 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment United States	70 participants n=70 Participants	70 participants n=70 Participants	140 participants n=140 Participants

PRIMARY outcome

Timeframe: during first 24 hours after surgery

The purpose of the study was to determine whether more patients undergoing craniotomies would not require any opioids (i.e., opioid consumption reduced to zero) during the first 24 postoperative hours when receiving intravenous (IV) acetaminophen during that time compared to those receiving placebo (normal saline).

Outcome measures

Measure	Acetaminophen n=66 Participants Subjects will receive 1000mg of intravenous acetaminophen every 6 hours for 24 hours beginning with dural closure. Acetaminophen	Placebo n=65 Participants Subjects will receive 100cc of normal saline every 6 hours for 24 hours beginning at dural closure. Placebo
Opioid Requirement After Surgery	10 Participants	4 Participants

SECONDARY outcome

Timeframe: 0 to 24 hours after surgery

Time (minutes) from end of procedure to first rescue dose in either PACU or ICU

Outcome measures

Measure	Acetaminophen n=66 Participants Subjects will receive 1000mg of intravenous acetaminophen every 6 hours for 24 hours beginning with dural closure. Acetaminophen	Placebo n=65 Participants Subjects will receive 100cc of normal saline every 6 hours for 24 hours beginning at dural closure. Placebo
Time to Rescue Medication in Both Groups	22 minutes Interval 16.5 to 33.0	37 minutes Interval 20.5 to 53.5

SECONDARY outcome

Timeframe: 0 to 24 hours after surgery

Outcome measures

Measure	Acetaminophen n=66 Participants Subjects will receive 1000mg of intravenous acetaminophen every 6 hours for 24 hours beginning with dural closure. Acetaminophen	Placebo n=65 Participants Subjects will receive 100cc of normal saline every 6 hours for 24 hours beginning at dural closure. Placebo
Amount of Rescue Medication in PACU in Both Groups	0.5 mg Interval 0.3 to 0.5	0.5 mg Interval 0.3 to 0.5

SECONDARY outcome

Timeframe: from 0 to estimated 24 hours after surgery

Outcome measures

Measure	Acetaminophen n=66 Participants Subjects will receive 1000mg of intravenous acetaminophen every 6 hours for 24 hours beginning with dural closure. Acetaminophen	Placebo n=65 Participants Subjects will receive 100cc of normal saline every 6 hours for 24 hours beginning at dural closure. Placebo
Median Difference in ICU Length of Stay/Hospital Length of Stay Between Both Groups Hospital Length of stay	71.75 hours Interval 49.0 to 118.0	75.5 hours Interval 50.0 to 119.0
Median Difference in ICU Length of Stay/Hospital Length of Stay Between Both Groups ICU length of stay	26 hours Interval 21.5 to 41.0	28 hours Interval 22.0 to 52.5

SECONDARY outcome

Timeframe: from 0 to estimated maximum of 24 hours after surgery

Population: As length of stay increased in ICU, the likelihood of discharge increased for the patients. This lowered the total amount of analyzed patients as the time increased.

Successful neurologic exams are performed by neurosurgical team during the first 24 hour period. Successful neurologic exams will be provided by a neurosurgical professional and they will answer Yes or No if the exam is appropriate.

Outcome measures

Measure	Acetaminophen n=66 Participants Subjects will receive 1000mg of intravenous acetaminophen every 6 hours for 24 hours beginning with dural closure. Acetaminophen	Placebo n=65 Participants Subjects will receive 100cc of normal saline every 6 hours for 24 hours beginning at dural closure. Placebo
Number of Participants Who Had a Successful Neurologic Exams Between Intervention and Placebo Group as Determined by a Neurosurgical Provider by Answering Either Yes or No ICU arrival	57 Participants	61 Participants
Number of Participants Who Had a Successful Neurologic Exams Between Intervention and Placebo Group as Determined by a Neurosurgical Provider by Answering Either Yes or No 8 Hours	63 Participants	64 Participants
Number of Participants Who Had a Successful Neurologic Exams Between Intervention and Placebo Group as Determined by a Neurosurgical Provider by Answering Either Yes or No 16 Hours	60 Participants	60 Participants
Number of Participants Who Had a Successful Neurologic Exams Between Intervention and Placebo Group as Determined by a Neurosurgical Provider by Answering Either Yes or No 24 Hours	53 Participants	55 Participants

SECONDARY outcome

Timeframe: from 0 to estimated maximum 24 hours after surgery

Temperature measure in degrees celcius during the first 24hours postoperatively in increments of 8 hours.

Outcome measures

Measure	Acetaminophen n=66 Participants Subjects will receive 1000mg of intravenous acetaminophen every 6 hours for 24 hours beginning with dural closure. Acetaminophen	Placebo n=65 Participants Subjects will receive 100cc of normal saline every 6 hours for 24 hours beginning at dural closure. Placebo
Median Difference in Temperature Between Intervention and Placebo Groups ICU Arrival	36.6 Degrees Celcius Interval 36.4 to 36.8	36.7 Degrees Celcius Interval 36.4 to 36.8
Median Difference in Temperature Between Intervention and Placebo Groups 8 Hours	36.7 Degrees Celcius Interval 36.5 to 36.9	36.8 Degrees Celcius Interval 36.6 to 37.0
Median Difference in Temperature Between Intervention and Placebo Groups 16 Hours	36.7 Degrees Celcius Interval 36.5 to 37.0	36.8 Degrees Celcius Interval 36.6 to 37.0
Median Difference in Temperature Between Intervention and Placebo Groups 24 Hours	36.8 Degrees Celcius Interval 36.6 to 37.0	36.7 Degrees Celcius Interval 36.5 to 37.0

SECONDARY outcome

Timeframe: during first 24 hours after surgery

Population: The amount of participants analyzed decreased as length of stay in the ICU increased as patients were likely discharged from the ICU. The median number indicates the RASS score and not the number of participants.

Sedation scores will be evaluated by providers through the Richmand-Agitation-Sedation Scale (RASS) system every 8 hours for the first 24hour postoperatively. The RASS is a 10 point scale with four levels for anxiety or agitation (+1 to +4 (indicates more agitation and alertness the higher number you have)), one level to indicate a calm and alert state (0), and 5 levels of deeper sedation (-1 to -5 ( the more negative number indicating a deeper level of sedation)) patients. It helps guide sedation therapy at the bedside. There are no worse outcomes with different levels of sedation scores. However, typically, we try to keep the scores in the range of 0-+1 to be able to appropriately assess patients and allow them to be mobile in a safe fashion.

Outcome measures

Measure	Acetaminophen n=66 Participants Subjects will receive 1000mg of intravenous acetaminophen every 6 hours for 24 hours beginning with dural closure. Acetaminophen	Placebo n=65 Participants Subjects will receive 100cc of normal saline every 6 hours for 24 hours beginning at dural closure. Placebo
Sedation Scores Measured by Richmand-Agitation-Sedation Scale (RASS) Every 8 Hours for 24 Hours in Both Groups ICU arrival	0 median of RASS scores Interval -1.0 to 0.0	0 median of RASS scores Interval -1.0 to 0.0
Sedation Scores Measured by Richmand-Agitation-Sedation Scale (RASS) Every 8 Hours for 24 Hours in Both Groups 8 hours	0 median of RASS scores Interval 0.0 to 0.0	0 median of RASS scores Interval 0.0 to 0.0
Sedation Scores Measured by Richmand-Agitation-Sedation Scale (RASS) Every 8 Hours for 24 Hours in Both Groups 16 hours	0 median of RASS scores Interval 0.0 to 0.0	0 median of RASS scores Interval 0.0 to 0.0
Sedation Scores Measured by Richmand-Agitation-Sedation Scale (RASS) Every 8 Hours for 24 Hours in Both Groups 24 hours	0 median of RASS scores Interval 0.0 to 0.0	0 median of RASS scores Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: during first 24 hours after surgery

Population: The median number below indicates the median VAS score.

Pain was measured using the Visual Analog Scale (VAS) for each patient at the time of arrival and every eight hours after arrival for the first 24 hours of ICU stay. A VAS score of 1 indicates little or no pain and a VAS score of 100 indicates severe pain.

Outcome measures

Measure	Acetaminophen n=66 Participants Subjects will receive 1000mg of intravenous acetaminophen every 6 hours for 24 hours beginning with dural closure. Acetaminophen	Placebo n=65 Participants Subjects will receive 100cc of normal saline every 6 hours for 24 hours beginning at dural closure. Placebo
Pain VAS Scores (1-100) Every 8 Hours for 24 Hours in Both Groups ICU Arrival	35 units on a scale Interval 20.0 to 60.0	50 units on a scale Interval 10.0 to 70.0
Pain VAS Scores (1-100) Every 8 Hours for 24 Hours in Both Groups 8 Hours	30 units on a scale Interval 10.0 to 50.0	45 units on a scale Interval 20.0 to 60.0
Pain VAS Scores (1-100) Every 8 Hours for 24 Hours in Both Groups 16 Hours	30 units on a scale Interval 10.0 to 50.0	30 units on a scale Interval 10.0 to 60.0
Pain VAS Scores (1-100) Every 8 Hours for 24 Hours in Both Groups 24 Hours	30 units on a scale Interval 10.0 to 50.0	20 units on a scale Interval 10.0 to 50.0

SECONDARY outcome

Timeframe: during first 24 hours after surgery

Population: As the time post surgery increased, the amount of individual participants discharged from the ICU increased.

Delirium was assessed in each of the participants upon arrival to the ICU using the Confusion Assessment Method for the ICU (CAM-ICU). The CAM-ICU was performed for each participant every 8 hours following admission for the first 24 hours

The CAM ICU scoring is based on a scale of 0-7, 0-2=no delirium, 3-5=miild delirium, 6-7=severe delirium. The positive CAM ICU consists of features 1 and 2 and either 3 or 4:

Features 1: Acute onset or fluctuating course Features 2: Inattention Features 3: Disorganized thinking Features 4: Altered level of consciousness

Outcome measures

Measure	Acetaminophen n=66 Participants Subjects will receive 1000mg of intravenous acetaminophen every 6 hours for 24 hours beginning with dural closure. Acetaminophen	Placebo n=65 Participants Subjects will receive 100cc of normal saline every 6 hours for 24 hours beginning at dural closure. Placebo
# of Participants With Delirium Measured by a Positive CAM-ICU Every 8 Hours for 24 Hours in Both Groups- ICU Arrival	1 Participants	0 Participants
# of Participants With Delirium Measured by a Positive CAM-ICU Every 8 Hours for 24 Hours in Both Groups- 8 Hours	0 Participants	0 Participants
# of Participants With Delirium Measured by a Positive CAM-ICU Every 8 Hours for 24 Hours in Both Groups- 16 Hours	0 Participants	0 Participants
# of Participants With Delirium Measured by a Positive CAM-ICU Every 8 Hours for 24 Hours in Both Groups- 24 Hours	0 Participants	0 Participants

SECONDARY outcome

Timeframe: During first 24 hours after surgery

on a verbal score 1-100, 1 would mean that the patient is not satisfied at all and 100 would mean that the patient was very satisfied.

Outcome measures

Measure	Acetaminophen n=66 Participants Subjects will receive 1000mg of intravenous acetaminophen every 6 hours for 24 hours beginning with dural closure. Acetaminophen	Placebo n=65 Participants Subjects will receive 100cc of normal saline every 6 hours for 24 hours beginning at dural closure. Placebo
Median Satisfaction Scores on a Verbal Score From 1(Not Satisfied at All) to 100 (Very Satisfied)	87.5 units on a scale Interval 55.0 to 100.0	80 units on a scale Interval 50.0 to 100.0

Adverse Events

Acetaminophen

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. Steven Greenberg

Northshore University Healthsystem, Evanston Hospital

Phone: 8475702760

Email: sbgreenb@gmail.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place