Perioperative Analgesia Using Gabapentin in Head and Neck Cancer Surgery

• ClinicalTrials.gov Identifier: NCT03682367
• Recruitment Status: Terminated
• First Posted: September 24, 2018
• Results First Posted: July 9, 2021
• Last Update Posted: July 9, 2021
• Sponsor: University of California, Davis
• Information provided by (Responsible Party): University of California, Davis

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Cancer of Head and Neck; Narcotic Use	Drug: Gabapentin; Drug: Placebo - Concentrate	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 8 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Masking Description: All staff involved including nursing, surgeons, pain management, participants and PI will be blinded. Unmasked personnel only include research pharmacy staff.
• Primary Purpose: Supportive Care
• Official Title: Perioperative Analgesia Using Gabapentin in Head and Neck Cancer Surgery: A Randomized Controlled Trial
• Actual Study Start Date: December 1, 2018
• Actual Primary Completion Date: April 1, 2020
• Actual Study Completion Date: April 6, 2020

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Control; 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.	Drug: Placebo - Concentrate; Use of sugar-free Placebo peri- and post-operatively.
Experimental: Intervention; 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.	Drug: Gabapentin; Use of Gabapentin peri- and post-operatively.; Other Names: Neurontin; Gralise; Horizant

Outcome Measures

Primary Outcome Measures :

1. Average Morphine Equivalent Units [ Time Frame: Perioperative. ]
   Determine the difference in average morphine equivalent units between experimental and control group.
2. Average Morphine Equivalent Units [ Time Frame: 1 week post-operation. ]
   Determine the difference in average morphine equivalent units between experimental and control group.
3. Average Morphine Equivalent Units [ Time Frame: 30 days post-operation. ]
   Determine the difference in average morphine equivalent units between experimental and control group.

Secondary Outcome Measures :

1. Pain Score (10 Point VAS) [ Time Frame: 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.
2. Post-operative Complications [ Time Frame: 30 days post-operation. ]
   Incidence of postoperative complications between experimental and control group.
3. Narcotics-related Complications [ Time Frame: 30 days post-operation. ]
   Incidence of narcotics-related complications between experimental and control group.
4. Inpatient Length of Stay [ Time Frame: 1 week post-operation. ]
   Determine the difference of average inpatient length of stay between experimental and control group.
5. Inpatient Cost [ Time Frame: 1 week post-operation. ]
   Determine the difference of average inpatient cost between experimental and control group.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

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

Contacts and Locations

Locations

United States, California

UC Davis Medical Center

Sacramento, California, United States, 95817

Sponsors and Collaborators

University of California, Davis

Investigators

• Principal Investigator: Arnaud Bewley, MD; University of California, Davis

  Study Documents (Full-Text)

Documents provided by University of California, Davis:

Study Protocol and Statistical Analysis Plan  [PDF] November 26, 2019

Informed Consent Form  [PDF] January 13, 2020

More Information

• Responsible Party: University of California, Davis
• ClinicalTrials.gov Identifier: NCT03682367
• Other Study ID Numbers: 1166778
• First Posted: September 24, 2018
• Results First Posted: July 9, 2021
• Last Update Posted: July 9, 2021
• Last Verified: July 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by University of California, Davis:

Gabapentin; Narcotic; Cancer; Placebo

Additional relevant MeSH terms:

Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Gabapentin; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anticonvulsants; Anti-Anxiety Agents; Tranquilizing Agents; Central Nervous System Depressants; Psychotropic Drugs; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antimanic Agents