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Supratentorial Brain TumorPhase 4NCT05763836

Comparison of the Analgesic Effects of Scalp Nerve Block and Intravenous Ibuprofen Applications Under the Guidance of Nociception Level Index (NoL) in Patients Undergoing Elective Supratentorial Craniotomy

A Phase 4 study testing Ibuprofen 800 Mg in 8 mL INTRAVENOUS INJECTION [Caldolor] and Scalp nerve block in people with Supratentorial Brain Tumor, run by Ankara University at 1 site in Turkey (Türkiye).

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

Introduction: Scalp incision is a powerful nociceptive stimulus that can exacerbate rapid changes in hemodynamic and sympathetic activity. Management of hemodynamic stability is essential in neuro-anesthesia and can be challenging among neurosurgery anesthesiologists. Read more about this study

Who is it for?
Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for
Supratentorial Brain Tumor
What is being tested?
Ibuprofen 800 Mg in 8 mL INTRAVENOUS INJECTION [Caldolor] and Scalp nerve block
Could I receive a placebo?
No, everyone receives an active treatment
How many people
102 participants
Where
1 siteTurkey (Türkiye)
Study dates
1 Nov 2022to 5 Mar 2023
Phase
Phase 4
Are there results?
None posted in the registry

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 65 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Undergoing elective suptatentorial craniotomy surgery
  • Body Mass Index (BMI) below 30
  • ASA I-III patient

Who cannot join

  • Patients with a history of allergic reaction to the drugs to be used in the study
  • Patients with heart, kidney and liver failure
  • Patients who refused to participate in the study

Trial locations and contacts

1 site in 1 country.

Turkey (Türkiye)1 site, 1 recruiting
  • Ankara University Fakulty of Medicine

    Ankara, Altındağ, 06100

    Ahmet C Ceran, +905310805423, ahmetcemceran38@gmail.com

    Recruiting

Other trials in Turkey (Türkiye)

About this study

Introduction: Scalp incision is a powerful nociceptive stimulus that can exacerbate rapid changes in hemodynamic and sympathetic activity. Management of hemodynamic stability is essential in neuro-anesthesia and can be challenging among neurosurgery anesthesiologists. Neurosurgery operations include steps with a lot of painful stimuli such as intubation, insertion of a head-pinning, and craniotomy. A good anesthetic technique can improve hemodynamic responses by reducing the incidence of complications such as intracranial hypertension, bleeding, and longer recovery time. Routine analgesic approach in the intraoperative and postoperative period of supratentorial craniotomy includes the routine use of paracetamol, opioids, scalp nerve block with proven effectiveness, and intravenous ibuprofen, which gives good results by reducing opioid doses in moderate-to-severe pain. Supratentorial craniotomy surgery, which requires tight hemodynamic control, needs effective analgesic methods.

Trial design: It is a prospective, randomized controlled, consisting of factorial groups, double-blind study.

Read more

Participants: This study will be carried out at Ankara University Faculty of Medicine İbni Sina Hospital (Altındağ, Ankara, Turkey) between November 2022 and February 2023. One hundred and two ASA I-III patients with a body mass index (BMI) below 30, aged between 18 and 65, who will undergo elective supratentorial craniotomy due to a brain tumor, are planned to be included in the study.

Interventions: The group in which IV ipurofen was administered was named Ibuprofen Group (Group I), the group in which scalp nerve block was applied Block Group (Group), and the group in which IV ibuprofen and scalp nerve block were applied together was named Ibuprofen+Block Group (IB Group). In the premedication unit, 800 mg of ibuprofen in 100 ml of normal saline will be administered to Group I and Group IB, and 100 ml of normal saline without ibuprofen will be administered to Group B as a 30-minute IV infusion. After intubation, a scalp nerve block with 20 ml of 0.5% bupivacaine will be applied to Group B and Group IB, and 20 ml of normal saline will be injected into the block sites in Group I.

Objective: The investigators aimed to show the effect of scalp nerve block and IV ibuprofen applications, which are routinely applied, on the optimization of the patient's process from induction to the early postoperative period. In addition, the investigators will examine the comparison of hemodynamic and analgesic effects of scalp nerve block and IV ibuprofen applications under the guidance of pain monitor, and their contribution to reducing opioid consumption, which has side effects such as postoperative nausea/vomiting, slowing of GI motility, respiratory depression.

Outcome: The primary endpoint of the study was the differences between the groups in the changes in the patients' nociception level (NoL) index, heart rate, and blood pressure parameters at the time of head-pinning and the first surgical skin incision.

Randomization: Randomization of the patients into 3 groups will be carried out using the closed envelope method.

Blinding: The patients included in the study and the practicing anesthesiologist do not know which patient is included in which group.

Read the detailed description

Scalp incision is a powerful nociceptive stimulus that can exacerbate rapid changes in hemodynamic and sympathetic activity. Management of hemodynamic stability is essential in neuro-anesthesia and can be challenging among neurosurgery anesthesiologists. A good anesthetic technique can improve hemodynamic responses by reducing the incidence of complications such as intracranial hypertension, bleeding, and longer recovery time. The stable hemodynamic not only provide an easy-to-perform surgical field, but also prevent serious complications such as bleeding, aneurysm rupture, and cerebral ischemia. In patients with impaired cerebral autoregulation, even a small increase in systemic arterial blood pressure can cause unexpected spikes in cerebral blood flow and intracranial pressure.

Neurosurgery operations include steps with a lot of painful stimuli such as intubation, insertion of a head-pinning, and craniotomy. In these patients where autoregulation may be impaired, it is extremely important to monitor the pain and provide adequate analgesia as well as providing sufficient depth of anesthesia in order to keep the hemodynamics stable.

Craniotomy consists of the steps of such as head-pinning in order to stabilize the head, making a skin incision, cutting the skull bone and removing the dura-mater and reaching the brain parenchyma. This process, which ends with the dura-mater incision, which the investigators define as the early intraoperative period, is the time period in which the most painful stimulus is observed, and accordingly, the increase in the level of vasoactive agents causes an increase in heart rate and blood pressure. In 86% of patients, there is pain of somatic origin, possibly involving soft tissue and pericranial muscles. Pain in this process is generally moderate to severe pain.

It has been reported that the pain after craniotomy is less than the pain after lumbar laminectomy for lumbar disc herniation. However, it has been shown that moderate-to-high pain may occur after craniotomy, especially in the first 2 hours postoperatively, and this is more common than previously thought. Increased oxygen consumption and catecholamine release caused by postoperative pain may predispose to intracranial hematomas by causing brain hyperemia and increased intracranial pressure. Local anesthetic infiltration or systemic analgesics such as non-steroidal anti-inflammatory drugs and opioids are used for craniotomy pain palliation. If the patient is conscious and feels pain after craniotomy, effective analgesia should be provided.

Routine analgesic approach in the intraoperative and postoperative period of supratentorial craniotomy includes the routine use of paracetamol, opioids, scalp nerve block with proven effectiveness, and intravenous (IV) ibuprofen, which gives good results by reducing opioid doses in moderate-to-severe pain. There are studies comparing drugs such as opioids, non-steroidal anti-inflammatory drugs (NSAIDs), ketamine, IV lidocaine, gabapentin in the prevention of the sympathetic response that occurs when entering the spiked cap and in the prevention of post-craniotomy pain and among these, scalp nerve block is accepted as the most effective analgesic approach.

Supratentorial craniotomy surgery, which requires tight hemodynamic control, needs effective analgesic methods. In this study, the investigators aimed to show the effect of scalp nerve block and IV ibuprofen applications, which are routinely applied, on the optimization of the patient's process from induction to the early postoperative period. In addition, the investigators will examine the comparison of hemodynamic and analgesic effects of scalp nerve block and IV ibuprofen applications under the guidance of pain monitor, and their contribution to reducing opioid consumption, which has side effects such as postoperative nausea/vomiting, slowing of GI motility, respiratory depression.

It is a prospective, randomized controlled, double-blind study. Randomization of the patients into 3 groups will be carried out using the closed envelope method. The group in which IV ipurofen was administered was named Ibuprofen Group (Group I), the group in which scalp nerve block was applied Block Group (Group), and the group in which IV ibuprofen and scalp nerve block were applied together was named Ibuprofen+Block Group (IB Group). The patients included in the study and the practicing anesthesiologist do not know which patient is included in which group.

Fentanyl (1-2 μg/kg) and propofol (2-3 mg/kg) will be used for anesthesia induction. Rocuronium (0.6 mg/kg) will be used as a muscle relaxant. Anesthesia maintenance will be provided with propofol and remifentanil infusion, keeping the bispectral index (BISTM) between 40-60 and the nociception level (NoL) index (PMD-200TM) between 10-25. The neuromuscular block depths of the patients will be monitored with train-of-four (TOF). As components of multimodal analgesia, 1 g paracetamol and 1.5 g magnesium sulfate will be administered as IV infusion to all patients after induction. Propofol and remifentanil infusions will be stopped after the end of the surgical procedure. Patients who have the appropriate level of consciousness and can perform simple commands will be extubated after the BIS value is above 80 and the TOF percentage is above 90.

In the premedication unit, 800 mg of ibuprofen in 100 ml of normal saline will be administered to Group I and Group IB, and 100 ml of normal saline without ibuprofen will be administered to Group B as a 30-minute IV infusion. After the infusion is over, the patients will be taken to the operating table. After the monitoring is completed, induction will be made and intubated.

After intubation, a scalp nerve block with 20 ml of 0.5% bupivacaine will be applied to Group B and Group IB, and 20 ml of normal saline will be injected into the block sites in Group I. Head stabilization will be achieved with a spiked head 5 minutes after the block application is completed. Normal saline solutions containing or not containing ibuprofen and the injectors used in the block will be prepared by the anesthesia technicians and the practicing anesthetist will be kept unaware of the content of the applied substance.

If the NoL value rises above 25 at all stages of the surgical process, an IV bolus of 0.5 mcg/kg remifentanil will be administered as a rescue analgesic.

Demographic characteristics such as the patient's name, surname, gender, age, weight, co-morbidities, American Society of Anesthesiologists (ASA) score will be recorded in the data collection form. In the intraoperative process, heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), NoL value, BIS value parameters will be recorded before intubation, after intubation, before head-pinning, after head-pinning, before surgical incision, after surgical incision, before craniotomy, after craniotomy, before dura mater incision, and after dura mater incision.

In the intraoperative process, the times when rescue analgesics are needed will be recorded.

SPSS 11.5 program will be used in the analysis of the data. Mean±standard deviation and median (minimum-maximum) will be used for quantitative variables, and the number of patients (percentage) for qualitative variables. The Kruskal Wallis H test will be used to determine whether there is a difference between the categories of a qualitative variable with more than two categories in terms of quantitative variables, since the assumptions of normal distribution are not provided. Chi-square and Fisher exact tests will be used when the relationship between two qualitative variables is desired. To look at the before-after differences of the same measurement, if normal distribution assumptions are provided, the Paired-t test will be used, otherwise the Wilcoxon Sign test will be used. Statistical significance level will be taken as 0.05.

Being tested
Ibuprofen 800 Mg in 8 mL INTRAVENOUS INJECTION [Caldolor], Scalp nerve block
Keywords
supratentorial craniotomy, scalp nerve block, intravenous ibuprofen, nociception level index, opioid reducing analgesia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Ibuprofen 800 Mg in 8 mL INTRAVENOUS INJECTION [Caldolor]Drug

    Intravenous ibuprofen infusion

  • Scalp nerve blockProcedure or surgery

    Scalp nerves blocked by using local anesthetics

Study groups in NCT05763836
Study groupRoleWhat they receive
Group BlockActive comparatorScalp nerve block applied group
Receives: Procedure: Scalp nerve block
Group IbuprofenExperimentalIntravenous ibuprofen applied group
Receives: Drug: Ibuprofen 800 Mg in 8 mL INTRAVENOUS INJECTION [Caldolor]
Grup Ibuprofen&BlockExperimentalBoth intravenous ibuprofen and scalp nerve block applied group
Receives: Drug: Ibuprofen 800 Mg in 8 mL INTRAVENOUS INJECTION [Caldolor]; Procedure: Scalp nerve block

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Nociception level (NoL) index

    In this study, the difference between the groups in the change of NoL values due to the procedures applied in supratentorial craniotomy surgery will be evaluated. NoL values range between 0 and 100. Values above 25 indicate that the patient has pain, and the value increases as the pain increases.

    Measured: From the beginning of the operation until the 3rd hour after the operation

Secondary outcomes (5)
  1. Heart rate

    In this study, the difference between the groups in the change of heart rate due to the procedures applied in supratentorial craniotomy surgery will be evaluated. It will be evaluated as beat per minute.

    Measured: Heart rate measurements will be recorded during surgery.

  2. Opioid consumption

    In the study, the amount of opioid consumed during surgery between groups will be compared. The amounts of remifentanil used as an opioid will be compared. The unit will be mcg.

    Measured: After the induction of anesthesia, opioid infusion will be started and continued until the operation is completed and the maintenance of anesthesia is terminated. At the end of the surgery, the total amount of opioid consumed will be recorded.

  3. Visual Analog Scale

    Patients will be asked to rate their pain status on a scale of 1 to 10 at 1, 2, and 3 hours after the end of surgery. Higher values indicate more pain.

    Measured: 1st, 2nd and 3rd hours after surgery

  4. Systolic blood pressure

    In this study, the difference between the groups in the change of systolic blood pressure due to the procedures applied in supratentorial craniotomy surgery will be evaluated. The unit will be mmHg.

    Measured: Systolic blood pressure measurements will be recorded during surgery.

  5. Dystolic blood pressure

    In this study, the difference between the groups in the change of dystolic blood pressure due to the procedures applied in supratentorial craniotomy surgery will be evaluated. The unit will be mmHg.

    Measured: Dystolic blood pressure measurements will be recorded during surgery.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Mar 2023
  2. Study start1 Nov 2022
  3. Primary completion1 Mar 2023 (estimated)
  4. Study completion5 Mar 2023 (estimated)

Resources

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
Prevention
Allocation
Randomised
Intervention model
Factorial
Masking
Double blind
Who is masked
Participant, Care provider
Enrolment
102 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05763836
Sponsor's protocol ID
AU-AUFM-MECO.CERAN.ERKOC-23001
Status last verified
Feb 2023
First submitted
8 Feb 2023
Last updated
10 Mar 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Data collected to reach outcomes will be shared.

Publications

  • Nemergut EC, Durieux ME, Missaghi NB, Himmelseher S. Pain management after craniotomy. Best Pract Res Clin Anaesthesiol. 2007 Dec;21(4):557-73. doi: 10.1016/j.bpa.2007.06.005.

    PubMed 18286837
  • Chen Y, Ni J, Li X, Zhou J, Chen G. Scalp block for postoperative pain after craniotomy: A meta-analysis of randomized control trials. Front Surg. 2022 Sep 26;9:1018511. doi: 10.3389/fsurg.2022.1018511. eCollection 2022.

    PubMed 36225222
  • Ban VS, Bhoja R, McDonagh DL. Multimodal analgesia for craniotomy. Curr Opin Anaesthesiol. 2019 Oct;32(5):592-599. doi: 10.1097/ACO.0000000000000766.

    PubMed 31306155
  • Vahabi S, Nadri S, Izadi F. The effects of gabapentin on severity of post spinal anesthesia headache. Pak J Pharm Sci. 2014 Sep;27(5):1203-7.

    PubMed 25176361
  • LASSEN NA. Cerebral blood flow and oxygen consumption in man. Physiol Rev. 1959 Apr;39(2):183-238. doi: 10.1152/physrev.1959.39.2.183. No abstract available.

    PubMed 13645234
  • Vahabi S, Rafieian Y, Abbas Zadeh A. The Effects of Intraoperative Esmolol Infusion on the Postoperative Pain and Hemodynamic Stability after Rhinoplasty. J Invest Surg. 2018 Apr;31(2):82-88. doi: 10.1080/08941939.2016.1278288. Epub 2017 Apr 4.

    PubMed 28375035
  • Hillman DR, Rung GW, Thompson WR, Davis NJ. The effect of bupivacaine scalp infiltration on the hemodynamic response to craniotomy under general anesthesia. Anesthesiology. 1987 Dec;67(6):1001-3. doi: 10.1097/00000542-198712000-00026. No abstract available.

    PubMed 3318562
  • Shiau JM, Chen TY, Tseng CC, Chang PJ, Tsai YC, Chang CL, Lee CG. Combination of bupivacaine scalp circuit infiltration with general anesthesia to control the hemodynamic response in craniotomy patients. Acta Anaesthesiol Sin. 1998 Dec;36(4):215-20.

    PubMed 10399517
  • Olsen KS, Pedersen CB, Madsen JB, Ravn LI, Schifter S. Vasoactive modulators during and after craniotomy: relation to postoperative hypertension. J Neurosurg Anesthesiol. 2002 Jul;14(3):171-9. doi: 10.1097/00008506-200207000-00001.

    PubMed 12172288
  • De Benedittis G, Lorenzetti A, Migliore M, Spagnoli D, Tiberio F, Villani RM. Postoperative pain in neurosurgery: a pilot study in brain surgery. Neurosurgery. 1996 Mar;38(3):466-9; discussion 469-70. doi: 10.1097/00006123-199603000-00008.

    PubMed 8837797
  • Vadivelu N, Kai AM, Tran D, Kodumudi G, Legler A, Ayrian E. Options for perioperative pain management in neurosurgery. J Pain Res. 2016 Feb 10;9:37-47. doi: 10.2147/JPR.S85782. eCollection 2016.

    PubMed 26929661
  • Dunbar PJ, Visco E, Lam AM. Craniotomy procedures are associated with less analgesic requirements than other surgical procedures. Anesth Analg. 1999 Feb;88(2):335-40. doi: 10.1097/00000539-199902000-00021.

    PubMed 9972752
  • Quiney N, Cooper R, Stoneham M, Walters F. Pain after craniotomy. A time for reappraisal? Br J Neurosurg. 1996 Jun;10(3):295-9. doi: 10.1080/02688699650040179.

    PubMed 8799542
  • Haldar R, Kaushal A, Gupta D, Srivastava S, Singh PK. Pain following craniotomy: reassessment of the available options. Biomed Res Int. 2015;2015:509164. doi: 10.1155/2015/509164. Epub 2015 Oct 1.

    PubMed 26495298
  • Hansen MS, Brennum J, Moltke FB, Dahl JB. Suboptimal pain treatment after craniotomy. Dan Med J. 2013 Feb;60(2):A4569.

    PubMed 23461986

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Ibuprofen 800 Mg in 8 mL INTRAVENOUS INJECTION [Caldolor] and Scalp nerve block in people with Supratentorial Brain Tumor, run by Ankara University at 1 site in Turkey (Türkiye).

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 3 inclusion and 3 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: status not confirmed, as of the sponsor's last update on 10 Mar 2023. 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 Turkey (Türkiye). 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?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Ahmet C Ceran (+905310805423, ahmetcemceran38@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Nociception level (NoL) index (time frame: From the beginning of the operation until the 3rd hour after the operation). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05763836, which also lists 18 linked publications.

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 10 Mar 2023; AzTrials last refreshed its copy on 8 Nov 2026.

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