Palmitoylethanolamide vs Ibuprofen for Pain After ESWL

Palmitoylethanolamide Versus Ibuprofen for Acute Postoperative Pain After Extracorporeal Shock Wave Lithotripsy: A Randomized Trial

Pain after extracorporeal shock wave lithotripsy (ESWL), a non-surgical procedure used to treat kidney stones, is common and is usually treated with non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen. However, NSAIDs may cause side effects in some patients, including stomach irritation and kidney problems.

Palmitoylethanolamide (PEA) is a naturally occurring substance in the body with anti-inflammatory and pain-relieving properties and has been shown to be safe in previous studies. This study aims to compare the effectiveness of PEA with ibuprofen for controlling acute postoperative pain after ESWL.

Participants undergoing ESWL will be randomly assigned to receive either oral PEA or oral ibuprofen. Pain intensity will be measured using a visual analogue scale during the first 24 hours after the procedure. The use of rescue pain medication and any side effects will also be recorded.

The results of this study may help determine whether PEA can be an effective alternative to ibuprofen for the management of acute pain after ESWL.

Study Overview

• Status: Not yet recruiting
• Conditions: Pain After Extracorporeal Shock Wave Lithotripsy; Palmitoylethanolamide
• Intervention / Treatment: Drug: Palmitoylethanolamide (PEA); Drug: Ibuprofen (Brufen®)

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Samar R Amin, M.D.; Phone Number: +201287793991; Email: samar.rafik@gmail.com

Study Locations

• Egypt
  • Qalyubia Governorate
    • Banhā, Qalyubia Governorate, Egypt, 13511
      • Benha University Hospital
      • Contact: Samar Amin, MD; Phone Number: +201287793991; Email: samar.rafik@gmail.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age 18-65 years
• ASA I or II
• Undergoing elective ESWL for renal or upper ureteric calculi
• Expected discharge same day or within 24 hours (outpatient ESWL).
• Able to provide informed consent and comply with study procedures (including diary/VAS recordings).
• Not currently taking chronic NSAIDs, opioids, or PEA supplements for ≥7 days prior to ESWL.

Exclusion Criteria:

• Chronic pain or daily analgesic use.
• Known allergy or contraindication to PEA, ibuprofen.
• Active peptic ulcer disease, known bleeding disorder, anticoagulant therapy
• Pregnancy or lactation.
• Use of steroids or other pain-modulating drugs.
• Severe renal impairment (eGFR <30 mL/min/1.73 m²).
• Hepatic failure or significant liver enzyme elevation (AST/ALT >3× ULN).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Palmitoylethanolamide Group; Participants assigned to this arm will receive oral palmitoylethanolamide for management of acute postoperative pain following extracorporeal shock wave lithotripsy (ESWL). Rescue analgesia will be available if required.	Drug: Palmitoylethanolamide (PEA); Palmitoylethanolamide (PEA) will be administered orally at a dose of 600 mg approximately 60 minutes before ESWL, followed by 600 mg every 8 hours for the first 24 hours after the procedure (total of three doses). PEA will be provided as a micronized or ultramicronized formulation. Participants will be allowed to receive rescue analgesia according to the study protocol if pain is not adequately controlled.
Active Comparator: Ibuprofen Group; Participants assigned to this arm will receive oral ibuprofen for management of acute postoperative pain following extracorporeal shock wave lithotripsy (ESWL). Rescue analgesia will be available if required.	Drug: Ibuprofen (Brufen®); Ibuprofen will be administered orally at a dose of 400 mg approximately 60 minutes before ESWL, followed by 400 mg every 8 hours for the first 24 hours after the procedure (total of three doses), in accordance with standard clinical practice. Participants will be allowed to receive rescue analgesia according to the study protocol if pain is not adequately controlled.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative pain intensity measured by Visual Analogue Scale (VAS)	Pain intensity will be assessed using a 10-cm visual analogue scale (VAS), where 0 indicates no pain and 10 indicates the worst imaginable pain. The primary comparison will be the VAS score measured 2 hours after extracorporeal shock wave lithotripsy (ESWL) between the palmitoylethanolamide and ibuprofen groups.	2 hours after ESWL

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain intensity over the first 24 hours after ESWL	Pain intensity will be assessed using the 10-cm visual analogue scale (VAS) at predefined time points after ESWL (e.g., recovery room, 30 minutes, 1 hour, 4 hours, 6 hours, 12 hours, and 24 hours) to evaluate pain progression over time.	From recovery room arrival up to 24 hours after ESWL
Time to first rescue analgesia	Time elapsed (in minutes) from completion of ESWL to the first administration of rescue analgesic medication for uncontrolled pain.	Up to 24 hours after ESWL
Total rescue analgesic consumption within 24 hours	Total amount of rescue analgesics administered within the first 24 hours after ESWL, recorded as grams of paracetamol and opioid consumption converted to morphine milligram equivalents (MME), if applicable.	Up to 24 hours after ESWL
Proportion of patients achieving clinically meaningful pain relief	The proportion of participants achieving at least a 30% and 50% reduction in pain intensity on the VAS compared with baseline or peak postoperative pain.	Within 24 hours after ESWL
Incidence of adverse events	The number and type of adverse events related to study medications, including gastrointestinal symptoms, renal-related symptoms, allergic reactions, or any other reported side effects.	From first dose of study medication up to 7 days after ESWL

Collaborators and Investigators

• Sponsor: Benha University

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2026
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: December 19, 2025
• First Submitted That Met QC Criteria: December 19, 2025
• First Posted (Actual): January 5, 2026

Study Record Updates

• Last Update Posted (Actual): January 5, 2026
• Last Update Submitted That Met QC Criteria: December 19, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Organic Chemicals; Carboxylic Acids; Acids, Carbocyclic; Phenylpropionates; Ibuprofen; palmidrol
• Other Study ID Numbers: RC.19.10.2025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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