Perioperative Analgesia on Postoperative Opioid Usage and Pain Control in H&N Cancer Surgery

Phase 3

Terminated

• Conditions: Postoperative Pain Control; Opioid Consumption
• Interventions: Drug: Placebo Ketamine; Drug: Ketamine; Drug: Placebo Lidocaine; Drug: Lidocaine; Drug: Placebo Acetaminophen; Drug: Acetaminophen; Drug: Placebo Gabapentin; Drug: Gabapentin; Drug: Placebo Celecoxib; Drug: Celecoxib

• Registration Number: NCT04176419
• Lead Sponsor: Case Comprehensive Cancer Center

Brief Summary

The purpose of this study is to determine how a non-opioid pain control regimen, administered before and during surgery, will affect postoperative pain control and total opioid consumption in head and neck cancer participants undergoing cancer surgery with free flap reconstruction.

Detailed Description

This study will help the study team determine how the experimental, non-opioid pain control regimen affects opioid-related side effects, participant satisfaction with pain management, PACU length of stay, hospital length of stay, chronic pain level, and chronic pain-related disability in participants, and to determine the safety and tolerability of the non-opioid pain control regimen in head and neck cancer patients undergoing cancer surgery with free flap reconstruction. Ketamine, Lidocaine, Acetaminophen, Gabapentin, and Celecoxib are FDA-approved drugs that have been approved for use individually, and have been used in combination for perioperative pain control. However, the use of these five drugs together in head and neck cancer patients undergoing free flap reconstruction has not been studied, which is why this study is experimental.

Study Timeline

• Study First Submitted: 2019-11-21
• Study First Submitted QC: 2019-11-22
• Study First Posted: 2019-11-25
• Study Start: 2020-01-17
• Primary Completion: 2021-06-23
• Study Completion: 2021-06-23
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-08
• Last Update Posted: 2024-11-12

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• Undergoing head & neck free flap reconstruction at the Cleveland Clinic Main Campus
• Subjects must have the ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria

• History of allergy to lidocaine, ketamine, acetaminophen, gabapentin, and/or celecoxib
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to Ketamine, Lidocaine or other agents used in this study
• Subjects receiving any other investigational agents
• Inadequate renal function (serum creatinine ≥ 2 mg/dl) within 30 days
• Inadequate hepatic function (total bilirubin ≥ 2 x the institutional ULN and/or AST or ALT ≥3 x the institutional ULN) within 30 days
• Known or suspected history of illicit drug abuse (including opioids but excluding tobacco and EtOH) within the past 6 months
• Pregnancy
• Contraindication to lidocaine (heart block, heart failure with EF < 30%) as determined by history of Congestive Heart Failure, or as determined by preoperative evaluation for surgical clearance
• In the opinion of the investigator, subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control Group	Placebo Ketamine	Perioperative placebo Placebo oral drugs will be encapsulated versions provided by the Investigational Drug Service and will appear identical to the interventional oral drugs. Placebo IV infusions will be prepared by Investigational Drug Service as per institutional guidelines and will appear identical to the interventional IV drugs.
Control Group	Placebo Lidocaine	Perioperative placebo Placebo oral drugs will be encapsulated versions provided by the Investigational Drug Service and will appear identical to the interventional oral drugs. Placebo IV infusions will be prepared by Investigational Drug Service as per institutional guidelines and will appear identical to the interventional IV drugs.
Control Group	Placebo Celecoxib	Perioperative placebo Placebo oral drugs will be encapsulated versions provided by the Investigational Drug Service and will appear identical to the interventional oral drugs. Placebo IV infusions will be prepared by Investigational Drug Service as per institutional guidelines and will appear identical to the interventional IV drugs.
Control Group	Placebo Gabapentin	Perioperative placebo Placebo oral drugs will be encapsulated versions provided by the Investigational Drug Service and will appear identical to the interventional oral drugs. Placebo IV infusions will be prepared by Investigational Drug Service as per institutional guidelines and will appear identical to the interventional IV drugs.
Control Group	Placebo Acetaminophen	Perioperative placebo Placebo oral drugs will be encapsulated versions provided by the Investigational Drug Service and will appear identical to the interventional oral drugs. Placebo IV infusions will be prepared by Investigational Drug Service as per institutional guidelines and will appear identical to the interventional IV drugs.
Treatment Group	Ketamine	Perioperative intervention (preoperative acetaminophen, gabapentin, and celecoxib and intraoperative ketamine and lidocaine). The Investigational Drug Service will mix and prepare the study medications necessary for each participant. An Investigational Drug Service staff member will deliver the oral medications to the nursing team in the preoperative holding unit and the IV medications to the anesthesia team in the OR unit.
Treatment Group	Lidocaine	Perioperative intervention (preoperative acetaminophen, gabapentin, and celecoxib and intraoperative ketamine and lidocaine). The Investigational Drug Service will mix and prepare the study medications necessary for each participant. An Investigational Drug Service staff member will deliver the oral medications to the nursing team in the preoperative holding unit and the IV medications to the anesthesia team in the OR unit.
Treatment Group	Acetaminophen	Perioperative intervention (preoperative acetaminophen, gabapentin, and celecoxib and intraoperative ketamine and lidocaine). The Investigational Drug Service will mix and prepare the study medications necessary for each participant. An Investigational Drug Service staff member will deliver the oral medications to the nursing team in the preoperative holding unit and the IV medications to the anesthesia team in the OR unit.
Treatment Group	Gabapentin	Perioperative intervention (preoperative acetaminophen, gabapentin, and celecoxib and intraoperative ketamine and lidocaine). The Investigational Drug Service will mix and prepare the study medications necessary for each participant. An Investigational Drug Service staff member will deliver the oral medications to the nursing team in the preoperative holding unit and the IV medications to the anesthesia team in the OR unit.
Treatment Group	Celecoxib	Perioperative intervention (preoperative acetaminophen, gabapentin, and celecoxib and intraoperative ketamine and lidocaine). The Investigational Drug Service will mix and prepare the study medications necessary for each participant. An Investigational Drug Service staff member will deliver the oral medications to the nursing team in the preoperative holding unit and the IV medications to the anesthesia team in the OR unit.

Primary Outcome Measures

Name	Time	Method
Total opioid consumption measured in daily morphine equivalent	at 48 hours postop	Total opioid consumption measured in daily morphine equivalent
Pain levels on Visual Analog Scale (VAS)	Pre-Op, 24 hours postop, and 48 hours postop	Change in pain levels on Visual Analog Scale (VAS 0-100mm scale with higher scores corresponding to more pain)

Secondary Outcome Measures

Name	Time	Method
Average Patient satisfaction with pain management scores	at the time of discharge (an average of 1 week)	Average scores for Internally-developed "patient satisfaction with pain management" questionnaire.; Domains include pain expected vs experienced, frequency of severe pain, promptness of care team, effectiveness of treatment, and future preferences; Domain scores range from 1-5 with higher scores mean worse outcomes (more severe pain, poor quality of care); Domains are distinct and are not summarized with a "total"score.
Average Opioid Related Symptom Distress Scale (ORSDS) scores	at 96 hours after surgery, and at discharge (an average of 1 week)	Average Opioid Related Symptom Distress Scale (ORSDS) scores; The OR-SDS is used to assess subject-reported levels of severity concerning 12 symptoms known to be associated with opioid medication usage. Symptom frequency, severity, and how bothersome symptom was is rated from 1-4 with higher . The average score for each symptom is calculated by taking the mean of patient-reported score. Total possible severity score: 0 (less severe) to 4 (more severe).
Time to first flatulence and defecation	an average of 7 days	Time to first flatulence and defecation from end of surgical case

Trial Locations

Locations (1)

Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center; 🇺🇸 Cleveland, Ohio, United States