Efficacy of Liposomal Bupivacaine Post Septorhinoplasty

• ClinicalTrials.gov Identifier: NCT05964868
• Recruitment Status: Enrolling by invitation
• First Posted: July 28, 2023
• Last Update Posted: February 13, 2024
• Sponsor: Jessyka Lighthall
• Information provided by (Responsible Party): Jessyka Lighthall, Milton S. Hershey Medical Center

Tracking Information

• First Submitted Date: July 6, 2023
• First Posted Date: July 28, 2023
• Last Update Posted Date: February 13, 2024
• Actual Study Start Date: February 5, 2024
• Estimated Primary Completion Date: October 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 19, 2023)

Differences in postoperative milligram morphine equivalents (MME) used between placebo and liposomal bupivacaine [ Time Frame: 6 months ]

Convert amount of opioid ingested to MMEs as an objective measure of post-operative narcotic use

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 3, 2023)

• Different in patient reported outcome measure of subjective pain scores based on a validated visual analog pain scale (subjective measure) between placebo and test drug [ Time Frame: 6 months ]
  Validated universal pain assessment tool: Wong-Baker pain scale pain questionnaire. Min 0 = no pain to 10 = maximum pain
• Difference in time to first dose of opioid rescue after surgery between placebo and test drug [ Time Frame: 6 months ]
  measure the time from leaving surgery to when the first dose of opioid is taken
• Difference in breathing outcomes between placebo and test drug [ Time Frame: 6 months ]
  NOSE questionnaire minimum 0 no obstruction to 100 complete obstruction
• Difference in adverse events/complications between placebo and test drug [ Time Frame: 6 months ]
  Assess for general adverse events and post-operative complications

Original Secondary Outcome Measures (submitted: July 19, 2023)

• Different in patient reported outcome measure of subjective pain scores based on a validated visual analog pain scale (subjective measure) between placebo and test drug [ Time Frame: 6 months ]
  Validated universal pain assessment tool: Wong-Baker pain scale pain questionnaire.
• Different in patient reported outcome measure of subjective pain scores based on a validated visual analog pain scale (subjective measure) between placebo and test drug [ Time Frame: 6 months ]
  Validated universal pain assessment tool: modified McGill pain questionnaire.
• Difference in time to first dose of opioid rescue after surgery between placebo and test drug [ Time Frame: 6 months ]
  measure the time from leaving surgery to when the first dose of opioid is taken
• Difference in breathing outcomes between placebo and test drug [ Time Frame: 6 months ]
  Assess for general adverse events, post-operative complications, and for local anesthsia NOSE questionnaire
• Difference in adverse events/complications between placebo and test drug [ Time Frame: 6 months ]
  Assess for general adverse events and post-operative complications

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy of Liposomal Bupivacaine Post Septorhinoplasty
• Official Title: The Efficacy of Liposomal Bupivacaine in the Management of Post-operative Pain Following Septorhinoplasty: A Single-blinded, Prospective Clinical Trial
• Brief Summary: The objective of this study is to determine if there is a difference in post-operative pain after septorhinoplasty when long-acting liposomal bupivacaine is used for local anesthesia compared to other standard local anesthetic regimens.

Detailed Description

Hypothesis: Patients receiving postoperative liposomal bupivacaine (EXPAREL®) at the surgical site after their septorhinoplasty will have better postoperative pain control and require fewer narcotics by means of a lower MME compared to the placebo group and the group that receives postoperative 0.25% bupivacaine with 1:200,000 epinephrine.

This a prospective randomized controlled, single-blind study evaluating the efficacy of EXPAREL® versus plain bupivacaine HCl and placebo after perinasal injections during septorhinoplasty procedures. Seventy-two total patients undergoing septorhinoplasty will be randomly distributed into three groups (20 patients per group) with various postoperative local anesthesia regimens. All groups will be given standard oral postoperative pain regimens as prescribed by the primary surgeon, typically consisting of alternating doses of 1000 mg acetaminophen and 800 mg ibuprofen with oxycodone 5 mg every 6 hours as needed for breakthrough pain. All three groups will receive the same treatment at the beginning of surgery with pre-incisional local surgical site injections with perinasal blocks of 1% lidocaine with 1:100,000 epinephrine. Group one (study group) will receive a five mL injection of EXPAREL® postoperatively, group two will receive a five mL injection of 0.25% bupivacaine with 1:200,000 epinephrine postoperatively, and group three will receive a five mL injection of saline along the surgical site, all in a ring block fashion (see illustration). This ring block involves nerve blocks to nasal branches of the supratrochlear, infraorbital, and infratrochlear nerves. This will also be injected into the floor of the nasal cavity to block branches of the nasopalatine nerve. The remainder of the ring block targets local infiltration surrounding the nose and injections are over bone. Although there is a potential risk of diffusion to adjacent cartilage, this risk is predicted to be low. Their use of postoperative pain medications will then be documented in the immediate postoperative period in the post-anesthesia care unit (PACU) as well as the following week postoperatively, every day, for three times a day. All groups will be required to fill electronic pain journals through RedCap (a HIPPA compliant server) to record consumption of pain medications and pain levels as reported by visual analog pain scales, the Wong-Baker FACES pain rating scale, and modified McGill pain questionnaire, all of which are validated tools for pain assessment. Patients will be subsequently followed over the course of six months postoperatively with these validated measures, use of pain medication, and by clinical exam of the nose/injection site including both external and internal nasal exam, palpation of the nose and cartilage grafts, evaluation static and dynamic function of the nose, and the presence of any adverse outcomes including but not limited to cartilage graft loss, septal perforation, synechiae formation, infection, and persistent or worsening nasal obstruction.

• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

This will be a randomized controlled, single-blinded study.

Masking: Triple (Participant, Care Provider, Investigator)
Masking Description:

The patient, surgeons, and research team will be blinded to the group that the subject was randomized to. The pharmacy will prepare equivalent drugs for each study group to visually appear similar so that blinding can be maintained. In the event if the patient experiences a concerning or an adverse reaction, the patient, the surgeons and the research team will be immediately unblinded from the study. If unblinding is required, the pharmacy will be notified and then will provide, from the randomization list, information as to which study group the patient was assigned.

Primary Purpose: Treatment

Condition

• Rhinoplasty
• Pain Management

Intervention

• Drug: Liposomal Bupivacaine
  Patients will receive post-operative liposomal bupivacaine (EXPAREL®) at the surgical site at the completion of their septorhinoplasty.
• Drug: 0.25% bupivacaine with 1:200,000 epinephrine
  Non-liposomal encapsulated bupivacaine at the surgical site at the completion of septorhinoplasty.
• Other: Placebo - Saline solution
  This group will receive a one-time 5 mL injection of saline post-operatively at the surgical site.

Study Arms

• Experimental: Liposomal Bupivacaine
  This group will receive a one time 5 mL injection of liposomal bupivacaine post-operatively at the surgical site.
  Intervention: Drug: Liposomal Bupivacaine
• Active Comparator: Bupivacaine with epinephrine
  This group will receive a one-time 5 mL injection of 0.25% bupivacaine with 1:200,000 epinephrine post-operatively at the surgical site.
  Intervention: Drug: 0.25% bupivacaine with 1:200,000 epinephrine
• Placebo Comparator: Saline solution
  This group will receive a one-time 5 mL injection of saline post-operatively at the surgical site.
  Intervention: Other: Placebo - Saline solution

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Enrolling by invitation
• Estimated Enrollment (submitted: July 19, 2023): 72
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2024
• Estimated Primary Completion Date: October 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Subject must be undergoing rhinoplasty or septorhinoplasty surgery
2. Male or female subjects greater than or equal to 18 years of age
3. Written informed consent must be obtained

Exclusion Criteria:

2. The subject is a pregnant or lactating 3. Patients have a cognitive impairment 4. Patient is a prisoner 5. Patients with hypersensitivity to local anesthetics and pain medications used in the study 6. Patients weighing less than 48 kg 7. Patients preoperatively taking narcotics for chronic pain 8. Patients with pre-existing painful conditions (complex regional pain syndrome, fibromyalgia, neuropathy) 9. Patients with liver dysfunction 10. Patients with increased creatinine (over 1.5 mg/dl) 11. Patients who have undergone autologous costal cartilage grafting with their rhinoplasty 12. Morbid obesity (BMI >40)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 99 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05964868
• Other Study ID Numbers: STUDY00020710
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Jessyka Lighthall, Milton S. Hershey Medical Center
• Original Responsible Party: Same as current
• Current Study Sponsor: Jessyka Lighthall
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Jessyka Lighthall, MD; Penn State Health

• PRS Account: Milton S. Hershey Medical Center
• Verification Date: February 2024