Intravenous Acetaminophen and Ketorolac for Pain Management During Extracorporeal Shockwave Lithotripsy

Intravenous Acetaminophen and Ketorolac for Pain Management During Extracorporeal Shockwave Lithotripsy: A Quasi-Randomized Controlled Trial

The goal of this clinical trial is to learn if a non-opioid pain medicine regimen works as well as or better than a standard opioid-based regimen to manage pain during extracorporeal shockwave lithotripsy (ESWL) in adults.

The main questions it aims to answer are: Does the non-opioid regimen lead to similar or better pain control during the procedure? Does the non-opioid regimen lead to similar or better procedure tolerability and side effect profile?

The non-opioid regimen will use intravenous (IV) midazolam plus IV acetaminophen and IV ketorolac, and the standard opioid-based regimen will use IV midazolam plus IV fentanyl.

Participants will be randomly assigned to receive one of the two medication regimens during ESWL, and asked to rate their pain before the procedure and 30 minutes after the procedure.

Study Overview

• Status: Enrolling by invitation
• Conditions: Extracorporeal Shockwave Lithotripsy
• Intervention / Treatment: Drug: IV midazolam; Drug: IV fentanyl; Drug: IV acetaminophen; Drug: IV ketorolac

Detailed Description

Extracorporeal shockwave lithotripsy (ESWL) is a common outpatient treatment for renal and ureteric stones, but the shockwaves can be painful and often require intra-procedure sedation and analgesia to improve comfort and allow delivery of an adequate number of shockwaves at therapeutic energy settings. Opioid-based regimens are widely used for ESWL because they are familiar, titratable, and effective; however, peri-procedural opioid exposure is increasingly scrutinized in the context of Canada's opioid crisis.

This study is a prospective quasi-randomized controlled trial in adults undergoing ESWL at St. Joseph's Hospital in Saint John, New Brunswick. The trial compares an opioid-sparing, multimodal regimen (intravenous midazolam, acetaminophen, and ketorolac) with a standard opioid-based regimen (intravenous midazolam and fentanyl). The primary objective is to evaluate the effectiveness of the non-opioid multimodal regimen on procedural pain compared with the standard opioid-based regimen. Secondary objectives include comparing shockwave tolerability and the adverse effect profile between regimens.

Participants are randomly allocated to a regimen and remain blinded to which regimen they receive. Sedation/analgesia is administered intravenously according to the assigned pathway, with midazolam titrated to achieve moderate sedation and analgesia provided via fentanyl (opioid arm) or a multimodal combination of ketorolac and acetaminophen (non-opioid arm).

Pain is measured using a 0-10 numeric rating scale (NRS). The NRS is administered before ESWL and 30 minutes after ESWL. Procedure tolerability is assessed using proxy measures recorded during ESWL (total shockwaves delivered and highest energy level achieved). Adverse medication effects recorded include hypotension, oxygen desaturations, and nausea/vomiting.

The overarching goal is to determine whether an opioid-sparing ESWL pathway can provide equal or superior pain control while maintaining comparable procedural tolerability and safety, supporting routine adoption of non-opioid multimodal analgesia when feasible.

• Study Type: Interventional
• Enrollment (Estimated): 266
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • New Brunswick
    • Saint John, New Brunswick, Canada, E2L 3L6
      • St. Joseph's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 19 years
• Undergoing ESWL
• Able to provide informed consent

Exclusion Criteria:

• Prior ESWL treatment in the past six months
• Narcotic use in the last 48 hours
• Allergy to midazolam, fentanyl, acetaminophen, or ketorolac
• Chronic kidney disease
• Solitary kidney
• Active peptic ulcer disease
• Concurrent anticoagulant prescription
• Liver disease
• Elevated liver function tests
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Opioid	Drug: IV midazolam; 1-2 mg; Drug: IV fentanyl; 25-300 mcg
Experimental: Non-Opioid	Drug: IV midazolam; 1-2 mg; Drug: IV acetaminophen; 1 g; Drug: IV ketorolac; 30 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain as Assessed by the NRS	The numeric rating scale (NRS) will be used to quantify pain. Scores range from 0 (no pain) to 10 (worst pain).	Before the procedure, and 30 minutes after the procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Procedure Tolerability as Assessed by Total Number of Shockwaves Delivered and Highest Energy Level Achieved		During the procedure
Rate of Adverse Medication Effects	Hypotension, oxygen desaturations, nausea/vomiting	During the procedure

Collaborators and Investigators

• Sponsor: Horizon Health Network
• Investigators: Principal Investigator: Thomas F Whelan, MD, FRCSC, Department of Urology - Horizon Health Network

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: January 20, 2026
• First Submitted That Met QC Criteria: January 20, 2026
• First Posted (Actual): January 27, 2026

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 7, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: pain; acetaminophen; ketorolac; intravenous; extracorporeal shockwave lithotripsy
• Additional Relevant MeSH Terms: Neurologic Manifestations; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Anilides; Amides; Aniline Compounds; Amines; Acetanilides; Piperidines; Indomethacin; Indoles; Benzazepines; Benzodiazepines; Acetaminophen; Ketorolac; Midazolam; Fentanyl
• Other Study ID Numbers: 6191

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No