CraniotomyPhase 4NCT01739699
The Efficacy of Intravenous Acetaminophen During Perioperative Neurosurgery Period
A Phase 4 study testing Acetaminophen in people with Craniotomy and Brain Surgery, run by Endeavor Health at 1 site in United States.
Trial summary
This is a prospective randomized double blinded trial study involving 128 patients undergoing any craniotomy procedure at Evanston Hospital. The patients will be randomized by the sealed envelope technique. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Craniotomy, Brain Surgery
- What is being tested?
- Acetaminophen
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 140 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2012to 20 Jan 2017
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject are able to provide informed consent prior to participation in the study
- Subjects must be scheduled to undergo elective open craniotomy procedure of > 2 hour duration
- Subjects must be >18 years old but less than 90 years old
- Subjects must have an American Society of Anesthesiologists (ASA) class I-IV
- Subjects must have the ability to communicate meaningfully with the investigator staff and read/understand the study procedures and the use of pain scales
Who cannot join
- Subjects used opioids or tramadol daily for >7 days before study medication administration
- Subjects had been treated with any of the following within 14 days of surgery: chaparral, comfrey, germander, jin bu huan, kava, pennyroyal, skullcap, St. John's wort, or valerian
- Subjects who have a chronic pain condition, significant medical disease or laboratory abnormality that in the investigator's judgment could compromise the subject's welfare
- Subjects with known hypersensitivity to opioids, acetaminophen or the inactive ingredients
- Subjects with known or suspected history of alcohol or drug abuse or dependence in the previous 2 years prior to the proposed surgery
Trial locations and contacts
1 site in 1 country.
United States1 site
NorthShore University HealthSystem
Evanston, Illinois, 60201
About this study
Official title: The Efficacy of Intravenous Acetaminophen During The Perioperative Period Of Neurosurgical Patients Undergoing Craniotomies
This is a prospective randomized double blinded trial study involving 128 patients undergoing any craniotomy procedure at Evanston Hospital. The patients will be randomized by the sealed envelope technique. The anesthesiologist and nurses who will be administering the placebo or intravenous acetaminophen will be blinded to the group in which patients are assigned.
The following general perioperative data will be recorded: patient information/preoperative data, procedural information, postoperative information, and overall satisfaction of pain management at 24 hours after surgery.
Based on a pilot study (N-20) we expect that 25% of the placebo treated patients will require no opioids in the first 24 hour postoperative period. With the use of intravenous acetaminophen, it is hypothesized that the number of patients that do not require opioids in the first 24 hours after surgery will double.
Read the detailed description
This is a prospective randomized double blinded trial study involving 128 patients undergoing any craniotomy procedure at Evanston Hospital. The patients will be randomized by the sealed envelope technique. The anesthesiologist and nurses who will be administering the placebo or intravenous acetaminophen will be blinded to the group in which patients are assigned.
The following information will be recorded for each patient enrolled in this study:
- Patient information/Preoperative Data
- Age, sex, height, weight,
- Disease specific information
- Primary diagnosis
- Pertinent medical history
- Medications
- Pertinent changes in patient status
- Procedural information
- Operation type
- Preoperative anesthetic medications
- Induction meds, intra-operative anesthetic meds, and post-operative anesthetic meds
- Duration of Surgery and Intubation
- Amount of dilaudid equivalent narcotics
- Postoperative Information
- Amount of narcotics administered in the PACU
- Amount of narcotics administered in the first 24 hour postoperative period
- Amount of non-narcotic analgesics administered in the first 24 hour postoperative period
- Time to first rescue analgesic in the PACU
- Amount of first rescue medication recorded
- Assessment of Pain Intensity at T0.5 (30min into PACU stay) and T24 (24 hours after end of surgery) (A 10-cm VAS scale will be used and labeled no pain at its left terminus and worst pain imaginable at its right terminus)
- Temperature in degrees centigrade every 8 hours for 24hours.
- CAM-ICU is performed by ICU nurses to detect delirium in patients every 8 hours and will be documented on a data collection sheet for the first 24 hours
- RASS is a sedation scoring system that is used in our ICU and is documented every 8 hours by ICU nursing. We will record the RASS score for the first 24 hours on a data collection sheet as documented by the ICU nurse.
- Overall satisfaction score at 24 hrs. "Overall satisfaction with pain management" (verbal rating score: scale 1 - 100)
Based on a pilot study (N-20) we expect that 25% of the placebo treated patients will require no opioids in the first 24 hour postoperative period. With the use of intravenous acetaminophen, it is hypothesized that the number of patients that do not require opioids in the first 24 hours after surgery will double.
- Conditions
- Craniotomy, Brain Surgery
- Being tested
- Acetaminophen, Placebo
- Keywords
- craniotomy, brain surgery, acetaminophen, Tylenol
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AcetaminophenDrug
Also called Tylenol
PlaceboDrug
Also called normal saline
| Study group | Role | What they receive |
|---|---|---|
| Acetaminophen | Experimental | Subjects will receive 1000mg of intravenous acetaminophen every 6 hours for 24 hours beginning with dural closure. Receives: Drug: Acetaminophen |
| Placebo | Other | Subjects will receive 100cc of normal saline every 6 hours for 24 hours beginning at dural closure. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Opioid Requirement 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).
Measured: during first 24 hours after surgery
Secondary outcomes (9)
Time to Rescue Medication in Both Groups
Time (minutes) from end of procedure to first rescue dose in either PACU or ICU
Measured: 0 to 24 hours after surgery
Amount of Rescue Medication in PACU in Both Groups
Measured: 0 to 24 hours after surgery
Median Difference in ICU Length of Stay/Hospital Length of Stay Between Both Groups
Measured: from 0 to estimated 24 hours after surgery
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
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.
Measured: from 0 to estimated maximum of 24 hours after surgery
Median Difference in Temperature Between Intervention and Placebo Groups
Temperature measure in degrees celcius during the first 24hours postoperatively in increments of 8 hours.
Measured: from 0 to estimated maximum 24 hours after surgery
Sedation Scores Measured by Richmand-Agitation-Sedation Scale (RASS) Every 8 Hours for 24 Hours in Both Groups
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.
Measured: during first 24 hours after surgery
Pain VAS Scores (1-100) Every 8 Hours for 24 Hours in Both Groups
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.
Measured: during first 24 hours after surgery
# of Participants With Delirium Measured by a Positive CAM-ICU Every 8 Hours for 24 Hours in Both Groups-
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
Measured: during first 24 hours after surgery
Median Satisfaction Scores on a Verbal Score From 1(Not Satisfied at All) to 100 (Very Satisfied)
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.
Measured: During first 24 hours after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2012 (estimated)
- Study startJan 2012
- Primary completion1 Aug 2016
- Study completion20 Jan 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for CraniotomyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 140 participants (actual)
Sponsor and investigators
- Lead sponsor
- Endeavor Health
- Sponsor type
- University, hospital or other
- Collaborators
- Cadence Pharmaceuticals
- Responsible party
- Principal investigator, Steven Greenberg, Endeavor Health
- Investigators
- Steven Greenberg, MD, Principal investigator, NorthShore University Health Sytem - Evanston Hospital Department of Anesthesia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01739699
- Sponsor's protocol ID
- EH11-380
- Status last verified
- May 2026
- First submitted
- 28 Nov 2012
- Last updated
- 22 Jun 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: Data is stored in file at our system
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Efficacy of Intravenous Acetaminophen During The Perioperative Period Of Neurosurgical Patients Undergoing Craniotomies
- ClinicalTrials.gov ID
- NCT01739699
- Acronym / sponsor ID
- EH11-380
- Conditions
- Craniotomy, Brain Surgery
- Keywords
- craniotomy, brain surgery, acetaminophen, Tylenol
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 140 participants (actual)
- Lead sponsor
- Endeavor HealthUniversity, hospital or other
- Collaborators
- Cadence Pharmaceuticals
- Study start
- Jan 2012
- Primary completion
- 1 Aug 2016 (actual)
- Study completion
- 20 Jan 2017 (actual)
- First posted
- 3 Dec 2012 (estimated)
- Results
- Posted 4 Nov 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a prospective randomized double blinded trial study involving 128 patients undergoing any craniotomy procedure at Evanston Hospital. The patients will be randomized by the sealed envelope technique. The anesthesiologist and nurses who will be administering the placebo or intravenous acetaminophen will be blinded to the group in which patients are assigned.
The following general perioperative data will be recorded: patient information/preoperative data, procedural information, postoperative information, and overall satisfaction of pain management at 24 hours after surgery.
Based on a pilot study (N-20) we expect that 25% of the placebo treated patients will require no opioids in the first 24 hour postoperative period. With the use of intravenous acetaminophen, it is hypothesized that the number of patients that do not require opioids in the first 24 hours after surgery will double.
Detailed description
This is a prospective randomized double blinded trial study involving 128 patients undergoing any craniotomy procedure at Evanston Hospital. The patients will be randomized by the sealed envelope technique. The anesthesiologist and nurses who will be administering the placebo or intravenous acetaminophen will be blinded to the group in which patients are assigned.
The following information will be recorded for each patient enrolled in this study:
- Patient information/Preoperative Data
- Age, sex, height, weight,
- Disease specific information
- Primary diagnosis
- Pertinent medical history
- Medications
- Pertinent changes in patient status
- Procedural information
- Operation type
- Preoperative anesthetic medications
- Induction meds, intra-operative anesthetic meds, and post-operative anesthetic meds
- Duration of Surgery and Intubation
- Amount of dilaudid equivalent narcotics
- Postoperative Information
- Amount of narcotics administered in the PACU
- Amount of narcotics administered in the first 24 hour postoperative period
- Amount of non-narcotic analgesics administered in the first 24 hour postoperative period
- Time to first rescue analgesic in the PACU
- Amount of first rescue medication recorded
- Assessment of Pain Intensity at T0.5 (30min into PACU stay) and T24 (24 hours after end of surgery) (A 10-cm VAS scale will be used and labeled no pain at its left terminus and worst pain imaginable at its right terminus)
- Temperature in degrees centigrade every 8 hours for 24hours.
- CAM-ICU is performed by ICU nurses to detect delirium in patients every 8 hours and will be documented on a data collection sheet for the first 24 hours
- RASS is a sedation scoring system that is used in our ICU and is documented every 8 hours by ICU nursing. We will record the RASS score for the first 24 hours on a data collection sheet as documented by the ICU nurse.
- Overall satisfaction score at 24 hrs. "Overall satisfaction with pain management" (verbal rating score: scale 1 - 100)
Based on a pilot study (N-20) we expect that 25% of the placebo treated patients will require no opioids in the first 24 hour postoperative period. With the use of intravenous acetaminophen, it is hypothesized that the number of patients that do not require opioids in the first 24 hours after surgery will double.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Acetaminophen | Experimental | Drug: AcetaminophenSubjects will receive 1000mg of intravenous acetaminophen every 6 hours for 24 hours beginning with dural closure. |
| Placebo | Other | Drug: PlaceboSubjects will receive 100cc of normal saline every 6 hours for 24 hours beginning at dural closure. |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Subject are able to provide informed consent prior to participation in the study
- Subjects must be scheduled to undergo elective open craniotomy procedure of > 2 hour duration
- Subjects must be >18 years old but less than 90 years old
- Subjects must have an American Society of Anesthesiologists (ASA) class I-IV
- Subjects must have the ability to communicate meaningfully with the investigator staff and read/understand the study procedures and the use of pain scales
Key exclusion criteria (5 listed)
- Subjects used opioids or tramadol daily for >7 days before study medication administration
- Subjects had been treated with any of the following within 14 days of surgery: chaparral, comfrey, germander, jin bu huan, kava, pennyroyal, skullcap, St. John's wort, or valerian
- Subjects who have a chronic pain condition, significant medical disease or laboratory abnormality that in the investigator's judgment could compromise the subject's welfare
- Subjects with known hypersensitivity to opioids, acetaminophen or the inactive ingredients
- Subjects with known or suspected history of alcohol or drug abuse or dependence in the previous 2 years prior to the proposed surgery
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AcetaminophenAlso: Tylenol | Drug | Acetaminophen |
| PlaceboAlso: normal saline | Drug | Placebo |
Primary outcome
Opioid Requirement After Surgery
Time frame: 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).
9 secondary outcomes
Time to Rescue Medication in Both Groups
Time frame: 0 to 24 hours after surgery
Amount of Rescue Medication in PACU in Both Groups
Time frame: 0 to 24 hours after surgery
Median Difference in ICU Length of Stay/Hospital Length of Stay Between Both Groups
Time frame: from 0 to estimated 24 hours after surgery
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
Time frame: from 0 to estimated maximum of 24 hours after surgery
Median Difference in Temperature Between Intervention and Placebo Groups
Time frame: from 0 to estimated maximum 24 hours after surgery
Sedation Scores Measured by Richmand-Agitation-Sedation Scale (RASS) Every 8 Hours for 24 Hours in Both Groups
Time frame: during first 24 hours after surgery
Pain VAS Scores (1-100) Every 8 Hours for 24 Hours in Both Groups
Time frame: during first 24 hours after surgery
# of Participants With Delirium Measured by a Positive CAM-ICU Every 8 Hours for 24 Hours in Both Groups-
Time frame: during first 24 hours after surgery
Median Satisfaction Scores on a Verbal Score From 1(Not Satisfied at All) to 100 (Very Satisfied)
Time frame: During first 24 hours after surgery
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. Data is stored in file at our system
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Steven Greenberg, MD principal investigator
NorthShore University Health Sytem - Evanston Hospital Department of Anesthesia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Acetaminophen in people with Craniotomy and Brain Surgery, run by Endeavor Health at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Nov 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Opioid Requirement After Surgery (time frame: during first 24 hours after surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2026.