Perioperative Pregabalin in Ureteroscopy

Perioperative Pregabalin as Part of a Multimodal Treatment Plan for Ureteral Stent Symptoms After Ureteroscopy: a Randomized Controlled Trial

This is a randomized, placebo-controlled, double-blinded study examining the use of perioperative pregabalin in ureteroscopy with stent placement. Ureteroscopy is typically performed for kidney or ureteral stones, but may be performed for other reasons such as for the diagnosis and possible treatment of certain kinds of cancers. As part of the same surgery, a ureteral stent is often placed. The surgery and the stent can cause discomfort, and patients may receive narcotic pain medicine. In other surgeries, a single dose of pregabalin, around one hour before surgery has been shown to decrease the need for pain medication after the surgery. This work will test whether this is true in ureteroscopy by giving eligible patients who agree to participate either pregabalin or a placebo shortly before surgery then examining how much pain medication they use after surgery. A placebo is an inactive medication. Neither the study participant nor the study staff will know who received pregabalin and who received placebo until after the study is over. For completing surveys, patients will receive compensation for their time in the form of gift certificates.

Study Overview

• Status: Active, not recruiting
• Conditions: Pain, Postoperative; Addiction; Opioid Use; Kidney Stone
• Intervention / Treatment: Drug: Pregabalin 300mg; Drug: Placebo oral tablet

Detailed Description

The prevalence of urolithiasis is greater than 8% and increasing in the United States. For those who require surgery, ureteroscopic treatment is common, representing >120,000 procedures yearly in the United States. This does not include ureteroscopy for other, including diagnosis of structural anomaly and diagnosis and management of ureteral and renal pelvic tumors. Frequently, a ureteral stent is placed intraoperatively. There is post-operative pain in around 80% of patients, and 12% of those undergoing ureteroscopy will have an emergency department visit in the first 30 post-operative days, typically for stent related symptoms or post procedural pain. Aside from the short-term repercussions of ureteroscopy with stent placement there are long-term issues related to pain and the treatment thereof. Recent evidence suggests that approximately 6% of opioid naïve patients who undergo ureteroscopy will become new persistent opioid users.

A single perioperative dose of pregabalin has been shown in many surgical contexts to have analgesic, anxiolytic, and opioid sparing effects. A common regimen employed in the literature is a single preoperative dose of 300mg PO pregabalin 1hr before induction of anesthesia. Pregabalin is a well-tolerated gabapentinoid medication with temporary cognition/coordination changes being the most common side effects. There is currently no standard of care for the use of perioperative gabapentinoid medication in ureteroscopy. A pilot was performed looking at such use that demonstrated the safety of this use and the feasibility of studying this at our institution.

In this work, the efficacy and safety of perioperative pregabalin in ureteroscopy with stent placement will be evaluated by executing a prospective, double blind, randomized, placebo-controlled trial for the use of perioperative pregabalin in the management of post-ureteroscopy symptoms, with the hypothesis that this treatment is safe and efficacious. Emphasis will be placed on patient-centered outcomes, especially those related to opioid sparing effects, mainly within the first 30 days after the surgery and extending out to one year.

The study will be powered with an 80% probability to detect a 10% difference in the primary outcomes. It will also assume a loss to follow up rate of 50%. This will require approximately 200 total subjects with a planned 1:1 placebo to active treatment enrollment ratio. The necessary enrollment can be accomplished in 11 months, allowing for 30 days of follow up within the funding period.

The final goal of this project will be at least one paper in a top urology journal. This will contribute to the literature by helping to inform urologists and anesthesiologists on the efficacy and safety of perioperative pregabalin for ureteroscopy with stent placement and will provide data regarding opioid sparing management after ureteroscopy. Opioid related issues abound nationwide and are evident in Missouri. This study has the potential to influence opioid use both in this state and nationwide as it relates to this frequently performed procedure.

• Study Type: Interventional
• Enrollment (Actual): 118
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Geoffrey H Rosen, MD; Phone Number: 5738824141; Email: rosenge@health.missouri.edu
• Study Contact Backup: Name: Katie Murray, DO; Email: murraykat@health.missouri.edu

Study Locations

• United States
  • Missouri
    • Columbia, Missouri, United States, 65212
      • University of Missouri-Columbia

Participation Criteria

Eligibility Criteria

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

Description

Subject Inclusion:

• Age >= 18 years
• Subject Population Undergoing elective ureteroscopy with stent placement at University of Missouri Hospital and affiliated facilities

Subject Exclusion:

• Renal insufficiency (eGFR < 60 mL/minute/1.73 m2)
• Chronic indwelling ureteral stent (>30 days in the previous year)
• Chronic opioid use
• History of opioid abuse
• Chronic gabapentinoid use
• History of gabapentinoid abuse
• Plan for inpatient hospitalization
• Pregnancy
• Inability of the patient to consent for themselves in English
• Allergy to gabapentinoid
• Liver failure or hepatic dysfunction

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pregabalin 300mg; Patient will receive a compounded version of 300mg pregabalin PO approximately one hour before surgery.	Drug: Pregabalin 300mg; Patient will receive a compounded version of 300mg pregabalin PO approximately one hour before surgery.; Other Names: Lyrica
Placebo Comparator: Placebo; Patient will receive a compounded version of inactive placebo PO approximately one hour before surgery.	Drug: Placebo oral tablet; Patient will receive a compounded version of inactive placebo PO approximately one hour before surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Visual analog scale of pain score	1 hour after arrival to post anesthesia care unit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oral morphine equivalents of opioids prescribed		Within the first 30 days post-operation
Proportion of patients with narcotic prescription		Within the first 30 days post-operation
Number of unplanned healthcare interactions	Unplanned healthcare interactions include unplanned visits, emergency room visits, admissions to the hospital, and phone calls	Within the first 30 days post-operation
Number of serious adverse events	Composite of unplanned serious adverse events including intensive care unit stay and death	Within the first 30 days post-operation
Proportion of patients reporting nausea or vomiting		1 hour after arrival to post anesthesia care unit
Watson clock drawing test score		1 hour after arrival to post anesthesia care unit

Other Outcome Measures

Outcome Measure	Time Frame
Baseline visual analog scale of pain score	In the pre-operative area before medication administration
Baseline Watson clock drawing test score	In the pre-operative area before medication administration

Collaborators and Investigators

• Sponsor: University of Missouri-Columbia
• Investigators: Principal Investigator: Katie Murray, DO, Assistant professor

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2020
• Primary Completion (Actual): July 1, 2023
• Study Completion (Estimated): July 1, 2024

Study Registration Dates

• First Submitted: October 8, 2019
• First Submitted That Met QC Criteria: October 8, 2019
• First Posted (Actual): October 10, 2019

Study Record Updates

• Last Update Posted (Actual): August 1, 2023
• Last Update Submitted That Met QC Criteria: July 27, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Postoperative Complications; Pain; Neurologic Manifestations; Pathological Conditions, Anatomical; Urolithiasis; Urinary Calculi; Calculi; Nephrolithiasis; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Pain, Postoperative; Kidney Calculi; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anti-Anxiety Agents; Anticonvulsants; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Pregabalin
• Other Study ID Numbers: 2017676

Drug and device information, study documents

• 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