Perioperative Analgesia Using Gabapentin in Head and Neck Cancer Surgery

• Sponsor: University of California, Davis (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03682367
• Collaborator: (none)
• Enrollment: 8
• Location: 1
• Arms: 2
• Actual Duration (Months): 16.2
• Patients Per Site Per Month: 0.5

Study Details

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
• 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: Dec 1, 2018
• Actual Primary Completion Date: Apr 1, 2020
• Actual Study Completion Date: Apr 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 [Perioperative.]

   Determine the difference in average morphine equivalent units between experimental and control group.

2. Average Morphine Equivalent Units [1 week post-operation.]

   Determine the difference in average morphine equivalent units between experimental and control group.

3. Average Morphine Equivalent Units [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) [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 [30 days post-operation.]

   Incidence of postoperative complications between experimental and control group.

3. Narcotics-related Complications [30 days post-operation.]

   Incidence of narcotics-related complications between experimental and control group.

4. Inpatient Length of Stay [1 week post-operation.]

   Determine the difference of average inpatient length of stay between experimental and control group.

5. Inpatient Cost [1 week post-operation.]

   Determine the difference of average inpatient cost between experimental and control group.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

	Site	City	State	Country	Postal Code
1	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)

• Study Protocol and Statistical Analysis Plan - Nov 26, 2019
• Informed Consent Form - Jan 13, 2020

More Information

Publications

None provided.

• Responsible Party: University of California, Davis
• ClinicalTrials.gov Identifier: NCT03682367
• Other Study ID Numbers: 1166778
• First Posted: Sep 24, 2018
• Last Update Posted: Jul 9, 2021
• Last Verified: Jul 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• 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; Gabapentin

Study Results

Participant Flow

Arm/Group Title	Control	Intervention
Arm/Group Description	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. Placebo - Concentrate: Use of sugar-free Placebo peri- and post-operatively.	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. Gabapentin: Use of Gabapentin peri- and post-operatively.
Period Title: Overall Study
STARTED	4	4
COMPLETED	2	0
NOT COMPLETED	2	4

Baseline Characteristics

Arm/Group Title	Control	Intervention	Total
Arm/Group Description	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. Placebo - Concentrate: Use of sugar-free Placebo peri- and post-operatively.	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. Gabapentin: Use of Gabapentin peri- and post-operatively.	Total of all reporting groups
Overall Participants	4	4	8
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	3 75%	2 50%	5 62.5%
>=65 years	1 25%	2 50%	3 37.5%
Sex: Female, Male (Count of Participants)
Female	1 25%	1 25%	2 25%
Male	3 75%	3 75%	6 75%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	4 100%	4 100%	8 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	4 100%	4 100%	8 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Average Morphine Equivalent Units
Description	Determine the difference in average morphine equivalent units between experimental and control group.
Time Frame	Perioperative.

Outcome Measure Data

Analysis Population Description

Due to safety concerns and patient non-compliance, the data was unreliable and uninterpretable.

Arm/Group Title	Control	Intervention
Arm/Group Description	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. Placebo - Concentrate: Use of sugar-free Placebo peri- and post-operatively.	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. Gabapentin: Use of Gabapentin peri- and post-operatively.
Measure Participants	0	0

2. Primary Outcome

Title	Average Morphine Equivalent Units
Description	Determine the difference in average morphine equivalent units between experimental and control group.
Time Frame	1 week post-operation.

Outcome Measure Data

Analysis Population Description

Due to safety concerns and patient non-compliance, the data was unreliable and uninterpretable.

Arm/Group Title	Control	Intervention
Arm/Group Description	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. Placebo - Concentrate: Use of sugar-free Placebo peri- and post-operatively.	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. Gabapentin: Use of Gabapentin peri- and post-operatively.
Measure Participants	0	0

3. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Due to safety concerns and patient non-compliance, the data was unreliable and uninterpretable.

Arm/Group Title	Control	Intervention
Arm/Group Description	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. Placebo - Concentrate: Use of sugar-free Placebo peri- and post-operatively.	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. Gabapentin: Use of Gabapentin peri- and post-operatively.
Measure Participants	0	0

4. Secondary Outcome

Title	Pain Score (10 Point VAS)
Description	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.
Time Frame	Perioperative, 1 week post-operation, 1 week post-discharge, and 30 days post-operation.

Outcome Measure Data

Analysis Population Description

Due to safety concerns and patient non-compliance, the data was unreliable and uninterpretable.

Arm/Group Title	Control	Intervention
Arm/Group Description	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. Placebo - Concentrate: Use of sugar-free Placebo peri- and post-operatively.	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. Gabapentin: Use of Gabapentin peri- and post-operatively.
Measure Participants	0	0

5. Secondary Outcome

Title	Post-operative Complications
Description	Incidence of postoperative complications between experimental and control group.
Time Frame	30 days post-operation.

Outcome Measure Data

Analysis Population Description

Due to safety concerns and patient non-compliance, the data was unreliable and uninterpretable.

Arm/Group Title	Control	Intervention
Arm/Group Description	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. Placebo - Concentrate: Use of sugar-free Placebo peri- and post-operatively.	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. Gabapentin: Use of Gabapentin peri- and post-operatively.
Measure Participants	0	0

6. Secondary Outcome

Title	Narcotics-related Complications
Description	Incidence of narcotics-related complications between experimental and control group.
Time Frame	30 days post-operation.

Outcome Measure Data

Analysis Population Description

Due to safety concerns and patient non-compliance, the data was unreliable and uninterpretable.

Arm/Group Title	Control	Intervention
Arm/Group Description	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. Placebo - Concentrate: Use of sugar-free Placebo peri- and post-operatively.	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. Gabapentin: Use of Gabapentin peri- and post-operatively.
Measure Participants	0	0

7. Secondary Outcome

Title	Inpatient Length of Stay
Description	Determine the difference of average inpatient length of stay between experimental and control group.
Time Frame	1 week post-operation.

Outcome Measure Data

Analysis Population Description

Due to safety concerns and patient non-compliance, the data was unreliable and uninterpretable.

Arm/Group Title	Control	Intervention
Arm/Group Description	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. Placebo - Concentrate: Use of sugar-free Placebo peri- and post-operatively.	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. Gabapentin: Use of Gabapentin peri- and post-operatively.
Measure Participants	0	0

8. Secondary Outcome

Title	Inpatient Cost
Description	Determine the difference of average inpatient cost between experimental and control group.
Time Frame	1 week post-operation.

Outcome Measure Data

Analysis Population Description

Due to safety concerns and patient non-compliance, the data was unreliable and uninterpretable.

Arm/Group Title	Control	Intervention
Arm/Group Description	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. Placebo - Concentrate: Use of sugar-free Placebo peri- and post-operatively.	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. Gabapentin: Use of Gabapentin peri- and post-operatively.
Measure Participants	0	0

Adverse Events

Time Frame	30 days
Adverse Event Reporting Description	Any known untoward event of any severity that occurs subsequent to the AE reporting period that the Investigator assesses as at least possibly related to the study therapy (i.e., the relationship cannot be ruled out) should also be reported as an AE.
Arm/Group Title	Control		Intervention
Arm/Group Description	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. Placebo - Concentrate: Use of sugar-free Placebo peri- and post-operatively.		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. Gabapentin: Use of Gabapentin peri- and post-operatively.
All Cause Mortality
	Control		Intervention
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/4 (0%)
Serious Adverse Events
	Control		Intervention
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/4 (0%)
Other (Not Including Serious) Adverse Events
	Control		Intervention
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		1/4 (25%)
Gastrointestinal disorders
Constipation	0/4 (0%)	0	1/4 (25%)	1
Nausea	0/4 (0%)	0	1/4 (25%)	1

Limitations/Caveats

Early study termination was decided after several technical issues regarding study logistics and patient non-compliance lead to unreliable and uninterpretable data.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.