Perioperative Analgesia Using Gabapentin in Head and Neck Cancer Surgery

Phase 3

Terminated

• Conditions: Narcotic Use; Cancer of Head and Neck
• Interventions: Drug: Placebo - Concentrate; Drug: Gabapentin

• Registration Number: NCT03682367
• Lead Sponsor: University of California, Davis

Brief Summary

Patients undergoing head and neck cancer surgery often have a lot of pain after surgery, which can lead to a need for a lot of narcotic pain medication. These medications can have many side effects that can make recovery more difficult including nausea, vomiting, dizziness, being overly sleepy, itchiness, inability to urinate, confusion, inability to have a bowel movement, longer time before being able to start walking. These side effects can make the hospital stay longer. The use of gabapentin, which is a non narcotic pain medication that focuses on nerve pain, has been used in smaller head and neck surgeries including removal of tonsils, sinus surgery, thyroid surgery. Studies in patients needing orthopedic or OB/Gyn surgery have shown improved pain control with gabapentin. Potential benefits to future patients include improved pain control, less narcotic associated side effects and faster functional recovery.

Detailed Description

Patients undergoing head and neck cancer surgery frequently experience significant post surgical pain, which often necessitates the use of narcotic pain medication. However, opioids can have multiple side effects that can complicate the head and neck cancer surgery patients postoperative care including nausea, vomiting, dizziness, sedation, pruritis, urinary retention, delirium, constipation, and time to ambulation. This, in turn, may affect patient length and cost of hospital stay. Consequently, a multimodal approach to analgesia is often employed with a focus on use of scheduled acetaminophen +/- NSAIDs supplemented with narcotics.

The use of gabapentin in the head and neck surgery literature has largely been limited to outpatient surgeries, including tonsillectomy in children and adults, functional endoscopic sinus surgery, and thyroidectomy. Indeed, a recent systematic review examined RCT comparing multimodal analgesia with gabapentin to analgesia without gabapentin in the otolaryngology literature. The majority of these studies employed preoperative dosing only, with only 1 study providing a single postoperative dose as well. The control group pain regimen among these studies did vary and included a combination of acetaminophen, NSAIDs, dexmedetomidine, or clonidine supplemented with opioids. The studies focused on the impact of gabapentin on acute postoperative pain determined by subjective measurement of reduction in visual analog pain scale. Of note, these patients were not hospitalized for longer than 24 hours. The thyroid and sinus studies consistently demonstrated improved pain control with use of gabapentin compared to control. The data was slightly more variable across the tonsillectomy studies. Moreover, 7 studies also measured the need for breakthrough pain medication and supplemental analgesia; each of these studies demonstrated significantly less supplemental analgesia consumption in the gabapentin group.

The only study examining the utility of gabapentin in pain management in head and neck cancer patients (glossectomy with anterolateral thigh free flap) examined the utility of a single preoperative dose. The authors concluded that this led to a significant reduction in subjective postoperative pain scores, morphine requirement, and nausea and vomiting compared to controls. This study did not employ postoperative gabapentin.

Furthermore, a recent meta analysis (133 RCT) examining literature across multiple surgical specialties pertaining to the efficacy of perioperative gabapentin supplementation vs placebo. The meta analysis indicated both the efficacy of gabapentin supplementation in decreasing opioid requirement (measured via morphine equivalent units) in the experimental group during the first 24 hours (P\<0.001), as well as a good safety profile across a wide range of loading and maintenance doses (200 to 1200 mg) of gabapentin. The significant reduction in opioid requirement was independent of surgery type. Moreover, the gabapentin group demonstrated a significant decrease in VAS postoperative pain scores, nausea, vomiting and itching; however, sedation scores were increased. Only 8 of these 133 RCT examined the effect of gabapentin outside the immediate 24 hour period, and all 8 trials demonstrated improvement in chronic pain scores at 3 months post-operatively. Finally, patient satisfaction scores and preoperative anxiety were also significantly improved with the use of gabapentin compared to controls.

Here, the investigators propose, for the first time, a superiority double blind randomized controlled placebo trial examining the effect of perioperative supplementation with gabapentin in head and neck cancer patients undergoing surgery. The primary purpose of this study is to determine the difference in morphine equivalent units between the experimental (i.e. perioperative gabapentin) and control group (i.e. no perioperative gabapentin). The secondary purpose of this study is to determine differences across the two groups in relation to the following: visual analog pain scores, cost and length of stay, medication side effects, and incidence of postoperative complications. Of note, in order to maximize reliability of the visual analog scale (VAS), prior studies have employed the Jadad scoring system, which the investigators will also implement in the study.

Study Timeline

• Study First Submitted: 2018-09-21
• Study First Submitted QC: 2018-09-21
• Study First Posted: 2018-09-24
• Study Start: 2018-12-01
• Primary Completion: 2020-04-01
• Study Completion: 2020-04-06
• Results First Submitted: 2021-06-03
• Status Verified: 2021-07
• Results First Submitted QC: 2021-07-08
• Last Update Submitted: 2021-07-08
• Results First Posted: 2021-07-09
• Last Update Posted: 2021-07-09

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 8

Inclusion Criteria

• Patients undergoing major head and neck surgery with concomitant free flap reconstruction surgery at UCDMC (oncology and non-oncologic): There will be two groups. Group 1 will include reconstruction with fibula free flap only. Group 2 will include any other free flap reconstruction, including scapular free flap, radial forearm free flap, anterolateral thigh free flap, anteromedial thigh free flap, and latissimus dorsi free flap.
• Patients naïve to gabapentin
• Adult patients >18 years of age and able to consent

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Exclusion Criteria

• Patients who are already taking scheduled gabapentin
• Patients allergic to gabapentin
• Chronic opioid use not from active head and neck cancer
• Illicit drug use (per report)
• Patients with known renal compromise, such that Creatinine clearance is < 30
• Patient with known hepatic insufficiency or cirrhosis
• Adults unable to consent
• Individuals less than 18 years old
• Pregnant women
• Prisoners

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control	Placebo - Concentrate	Standard of care use of perioperative analgesia with acetaminophen and opioids that is supplemented with placebo solution. Participants will then be discharged after surgery with postoperative acetaminophen, opioids, and placebo.
Intervention	Gabapentin	Interventional use of perioperative analgesia with acetaminophen and opioids that is supplemented with gabapentin solution. Participants will then be discharged after surgery with postoperative acetaminophen, opioids, and gabapentin.

Primary Outcome Measures

Name	Time	Method
Average Morphine Equivalent Units	30 days post-operation.	Determine the difference in average morphine equivalent units between experimental and control group.

Secondary Outcome Measures

Name	Time	Method
Inpatient Length of Stay	1 week post-operation.	Determine the difference of average inpatient length of stay between experimental and control group.
Post-operative Complications	30 days post-operation.	Incidence of postoperative complications between experimental and control group.
Narcotics-related Complications	30 days post-operation.	Incidence of narcotics-related complications between experimental and control group.
Inpatient Cost	1 week post-operation.	Determine the difference of average inpatient cost between experimental and control group.
Pain Score (10 Point VAS)	Perioperative, 1 week post-operation, 1 week post-discharge, and 30 days post-operation.	Determine average change of inpatient Pain Score Visual Analog Scale (VAS) on a standardized 1 (no pain) to 10 (highest level of pain) scale between experimental and control groups.

Trial Locations

Locations (1)

UC Davis Medical Center; 🇺🇸 Sacramento, California, United States