Flurbiprofen Axetil as an Adjuvant to Pre-emptive Scalp Infiltration

Flurbiprofen Axetil as an Adjuvant to Pre-emptive Scalp Infiltration for Post-craniotomy Pain

Post-craniotomy pain remains a major challenge in patient care following neurosurgery.Flurbiprofen axetil (FA), as an injectable nonselective cyclooxygenase inhibitor, is a widely prescribed NSAID for postoperative pain. As FA is highly lipophilic by merging into emulsified lipid microspheres, it has a high affinity to the surgical incision and inflammatory tissues to achieve targeted drug therapy and prolonged duration of action, thus providing a basis for its local use to achieve efficacy and safety comparable to or greater than systemic administration. In this study, we attempt to evaluate the clinical effects of FA as an adjunct to ropivacaine in pre-emptive scalp infiltration to prevent or reduce pain after craniotomy.

Study Overview

• Status: Suspended
• Conditions: Postoperative Pain
• Intervention / Treatment: Drug: FA plus ropivacaine; Drug: ropivacaine alone

• Study Type: Interventional
• Enrollment (Estimated): 216
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Beijing Tiantan Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age minimum 18 years;
2. ASA physical status of I - II;
3. Body mass index (BMI) of 15 - 30;
4. Scheduled for supratentorial craniotomy under general anesthesia;
5. Anticipated tracheal extubation, recovery of consciousness and orientation within 2 hours after craniotomy.

Exclusion Criteria:

1. Glasgow Coma Scale <15;
2. Unable to use the PCIA device or comprehend the pain NRS;
3. History of opioid dependence, chronic headache or intake of any drugs with known analgesic properties within the 24 hours before surgery;
4. History of craniotomy or scalp infection;
5. Any contraindication to flurbiprofen axetil, such as gastrointestinal ulcer, coagulation disorders, renal dysfunction, heart failure and ischemic heart disease;
6. History of allergy to any drug used in the study;
7. Pregnancy and breastfeeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ropivacaine plus FA; 5 mL FA (50 mg; by Beijing Taide Pharmaceutical Co., Ltd) and 15 mL of 1% ropivacaine (Nai Le Pin 10mg/mL; by AstraZeneca AB, Sweden) diluted to a total volume of 30 mL in normal saline	Drug: FA plus ropivacaine; Th group will receive 0.17% FA and 0.5% ropivacaine for pre-emptive scalp infiltration at about 30 min before surgical incision. The assigned solution was injected along the planned surgical incision and pin fixation sites of the Mayfield head holder, using a 22-gauge needle introduced throughout the entire thickness of the scalp at a 45° angle.
Active Comparator: ropivacaine alone; 15 mL of 1% ropivacaine diluted to a total volume of 30 mL in normal saline	Drug: ropivacaine alone; The ropivacaine alone group will receive 0.5% ropivacaine alone for pre-emptive scalp infiltration at about 30 min before surgical incision. The assigned solution was injected along the planned surgical incision and pin fixation sites of the Mayfield head holder, using a 22-gauge needle introduced throughout the entire thickness of the scalp at a 45° angle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total consumption of sufentanil with PCIA device at 48 hours postoperatively.	A postoperative Patient Controlled Intravenous Analgesia (PCIA) pump containing sufentanil 200μg in 100 mL saline will be administered from admission to the PACU until postoperative 48 hours. The PCIA pump will be set for 0.5 mL bolus doses with a lockout time of 15 min without initial dose or continuous infusion. The maximum dose will be limited to 2 mL (sufentanil 4 μg) per hour.	at 48 hours postoperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain NRS scores at 2 hours after craniotomy	0 indicates no pain and 10 indicates the worst pain imaginable	at 2 hours after craniotomy
Pain NRS scores at 4 hours after craniotomy	0 indicates no pain and 10 indicates the worst pain imaginable	at 4 hours after craniotomy
Pain NRS scores at 12 hours after craniotomy	0 indicates no pain and 10 indicates the worst pain imaginable	at 12 hours after craniotomy
Pain NRS scores at 24 hours after craniotomy	0 indicates no pain and 10 indicates the worst pain imaginable	at 24 hours after craniotomy
Pain NRS scores at 48 hours after craniotomy	0 indicates no pain and 10 indicates the worst pain imaginable	at 48 hours after craniotomy
The time to first prescription of OC/APAP after craniotomy	In the ward, if a patient scores > 4 in pain NRS after receiving a maximum dose of 2 mL per hour from PCIA device, an oral supplementary tablet of oxycodone (OC)/acetaminophen (APAP) (5/325 mg; by MallinckrodtInc, USA) will be prescribed as a rescue analgesic at an interval of at least 6 hours.	up to 48 hours after craniotmy
Hospital duration after craniotomy	The duration from end of surgery to discharge from hospital	From surgery day until the discharge date from hospital, assessed up to one week
WHOQOL-BREF score	It is a questionnaire consisting of social relationships, physical health, psychological health, environment, overall QoL and general health. The mean score of each domain ranges between 4 and 20. A higher score indicates a better QoL	at 1month after craniotomy
WHOQOL-BREF score	It is a questionnaire consisting of social relationships, physical health, psychological health, environment, overall QoL and general health. The mean score of each domain ranges between 4 and 20. A higher score indicates a better QoL	at 3 months after craniotomy
PONV scores	It is rated as: 0, absent; 1, nausea not requiring treatment; 2, nausea requiring treatment; 3, vomiting	at 24 hours after surgery
PONV scores	It is rated as: 0, absent; 1, nausea not requiring treatment; 2, nausea requiring treatment; 3, vomiting	at 48 hours after surgery
Wound healing score	It is rated as excellent, good and suboptimal	at 1 month after craniotomy
Wound healing score	It is rated as excellent, good and suboptimal	at 3 months after craniotomy
Patient and Observer Scar Assessment Scale	It consists of 2 numeric scales regarding the observer component (6 items) and the patient component (6 items). All included items are scored on the same 10-point scale. And a higher score represents a poorer scar quality.	at 1 month after craniotomy
Patient and Observer Scar Assessment Scale	It consists of 2 numeric scales regarding the observer component (6 items) and the patient component (6 items). All included items are scored on the same 10-point scale. And a higher score represents a poorer scar quality.	at 3 months after craniotomy
The occurrence of other AEs	Other AEs include cerebral hematoma, respiratory depression, gastrointestinal ulcerations and perforation, renal risks, coagulation dysfunction, allergic reaction and wound infection, oozing, hemorrhage, burning sensation and mild pruritus	throughout both the treatment and follow-up periods (up to 3 months)
Total consumption of sufentanil with PCIA pump at 24 hours after craniotomy	A postoperative Patient Controlled Intravenous Analgesia (PCIA) pump containing sufentanil 200μg in 100 mL saline will be administered from admission to the PACU until postoperative 48 hours. The PCIA pump will be set for 0.5 mL bolus doses with a lockout time of 15 min without initial dose or continuous infusion. The maximum dose will be limited to 2 mL (sufentanil 4 μg) per hour.	at 24 hours postoperatively
Time to first PCIA button press after craniotomy	A postoperative Patient Controlled Intravenous Analgesia (PCIA) pump containing sufentanil 200μg in 100 mL saline will be administered from admission to the PACU until postoperative 48 hours. The PCIA pump will be set for 0.5 mL bolus doses with a lockout time of 15 min without initial dose or continuous infusion. The maximum dose will be limited to 2 mL (sufentanil 4 μg) per hour.	after craniotomy
Pain NRS scores at 1 mon after craniotomy	0 indicates no pain and 10 indicates the worst pain imaginable	at 1 mon after craniotomy
Pain NRS scores at 3 mons after craniotomy	0 indicates no pain and 10 indicates the worst pain imaginable	at 3 mons after craniotomy

Collaborators and Investigators

• Sponsor: Beijing Tiantan Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2023
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: November 7, 2022
• First Submitted That Met QC Criteria: November 17, 2022
• First Posted (Actual): November 22, 2022

Study Record Updates

• Last Update Posted (Estimated): October 6, 2025
• Last Update Submitted That Met QC Criteria: September 30, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain, Postoperative; Organic Chemicals; Anilides; Amides; Aniline Compounds; Amines; Ropivacaine
• Other Study ID Numbers: 2018-034-02-10

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No