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

• ClinicalTrials.gov Identifier: NCT04176419
• Recruitment Status: Recruiting
• First Posted: November 25, 2019
• Last Update Posted: May 13, 2022
• Sponsor: Case Comprehensive Cancer Center
• Information provided by (Responsible Party): Case Comprehensive Cancer Center

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Postoperative Pain Control; Opioid Consumption	Drug: Ketamine; Drug: Placebo Ketamine; Drug: Lidocaine; Drug: Placebo Lidocaine; Drug: Acetaminophen; Drug: Placebo Acetaminophen; Drug: Gabapentin; Drug: Placebo Gabapentin; Drug: Celecoxib; Drug: Placebo Celecoxib	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 292 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Supportive Care
• Official Title: Investigating the Effect of a Perioperative Analgesia Protocol on Postoperative Opioid Usage and Pain Control in Patients Undergoing Major Head and Neck Cancer Surgery Requiring Microvascular Free Flap Reconstruction
• Actual Study Start Date: January 17, 2020
• Estimated Primary Completion Date: December 2022
• Estimated Study Completion Date: December 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Treatment Group; 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.	Drug: Ketamine; 0.25 mg/kg IV bolus before incision, followed by 0.005 mg/kg/minute IV for the remainder of the surgical case excluding the final 30-45 minutes.; Other Names: Ketamine Hydrochloride; Ketamine Hydrochloride Injection; USP; Drug: Lidocaine; 1.5 mg/kg IV bolus before incision, followed by infusion of 1.5 mg/kg/hour ideal body weight (max 8 hours) during the case; Other Names: Lidocaine Hydrochloride and 5% dextrose; lidocaine hydrochloride injection; Drug: Acetaminophen; 1,000 mg orally at time of check-in to the preoperative unit; Other Names: Paracetamol; Tylenol; N-acetyl-para-aminophenol; APAP; Drug: Gabapentin; 600 mg orally at time of check in to the preoperative unit; Other Name: Neurontin; Drug: Celecoxib; 200 mg orally at time of check in to the preoperative unit; Other Name: Celebrex
Placebo Comparator: Control Group; 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.	Drug: Placebo Ketamine; 0.25 mg/kg IV bolus before incision, followed by 0.005 mg/kg/minute IV for the remainder of the surgical case excluding the final 30-45 minutes.; Drug: Placebo Lidocaine; 1.5 mg/kg IV bolus before incision, followed by infusion of 1.5 mg/kg/hour ideal body weight (max 8 hours) during the case; Drug: Placebo Acetaminophen; 1,000 mg orally at time of check-in to the preoperative unit; Drug: Placebo Gabapentin; 600 mg orally at time of check in to the preoperative unit; Drug: Placebo Celecoxib; 200 mg orally at time of check in to the preoperative unit

Outcome Measures

Primary Outcome Measures :

1. Total opioid consumption measured in daily morphine equivalent [ Time Frame: at 48 hours postop ]
   Total opioid consumption measured in daily morphine equivalent
2. Pain levels on Visual Analog Scale (VAS) [ Time Frame: 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 :

1. Average Opioid Related Symptom Distress Scale (ORSDS) scores [ Time Frame: 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).

2. Average Patient satisfaction with pain management scores [ Time Frame: 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.

3. Time to first flatulence and defecation [ Time Frame: an average of 7 days ]
   Time to first flatulence and defecation from end of surgical case

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:

• 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

Contacts and Locations

Contacts

Contact: Jamie Ku, MD; 1-866-223-8100; TaussigResearch@ccf.org

Locations

United States, Ohio

Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center; Recruiting

Cleveland, Ohio, United States, 44195

Contact: Jamie Ku, MD 866-223-8100 TaussigResearch@ccf.org

Contact: Brian Matia +1 216-445-8748 matiab@ccf.org

Sponsors and Collaborators

Case Comprehensive Cancer Center

Investigators

• Principal Investigator: Jamie Ku, MD; Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

More Information

• Responsible Party: Case Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: NCT04176419
• Other Study ID Numbers: CASE6319
• First Posted: November 25, 2019
• Last Update Posted: May 13, 2022
• Last Verified: May 2022

• 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 Case Comprehensive Cancer Center:

Head & neck cancer; Microvascular free flap reconstruction

Additional relevant MeSH terms:

Pain, Postoperative; Postoperative Complications; Pathologic Processes; Pain; Neurologic Manifestations; Acetaminophen; Celecoxib; Lidocaine; Ketamine; Gabapentin; Anesthetics, Local; Anesthetics; Central Nervous System Depressants; Physiological Effects of Drugs; Sensory System Agents; Peripheral Nervous System Agents; Anti-Arrhythmia Agents; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Analgesics; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Neurotransmitter Agents; Analgesics, Non-Narcotic; Antipyretics