Tapentadol vs Pregabalin for Postoperative Pain in Lower Limb Surgery

Oral Premedication With Tapentadol Versus Pregabalin for Acute Postoperative Pain in Lower Limb Surgery Under Neuraxial Anesthesia: A Pilot Randomized Controlled Trial

This pilot randomised controlled trial compared 72-hour oral premedication with tapentadol (50 mg every 12 hours) versus pregabalin (75 mg every 24 hours) for preventing acute postoperative pain in 46 patients undergoing elective lower limb surgery under neuraxial anaesthesia. The primary outcome was pain intensity measured by the Numeric Rating Scale (NRS 0-10) at PACU arrival and at 30, 60, 90, and 120 minutes thereafter. Secondary outcomes included Verbal Rating Scale scores, rescue morphine consumption, and safety (nausea/vomiting, hypersensitivity).

Study Overview

• Status: Completed
• Conditions: Acute Postoperative Pain; Lower Limb Surgery
• Intervention / Treatment: Drug: Tapentadol; Drug: Pregabalin

Detailed Description

Acute postoperative pain affects over 80% of surgical patients, with orthopaedic lower limb procedures causing particularly severe pain. Preemptive analgesia may attenuate central sensitisation before surgical incision. Tapentadol (μ-opioid agonist + norepinephrine reuptake inhibitor) and pregabalin (voltage-gated calcium channel modulator) are pharmacologically distinct options, but direct comparative data are lacking.

This single-centre, double-blind, parallel-group pilot randomised controlled trial was conducted at Hospital Regional "General Ignacio Zaragoza," ISSSTE, Mexico City. Forty-six patients (ASA I-II, age 18-50 years, BMI 18-35 kg/m²) scheduled for elective lower limb surgery under neuraxial anaesthesia were randomised 1:1 to receive either tapentadol 50 mg orally every 12 hours (n=23) or pregabalin 75 mg orally every 24 hours (n=23), both initiated 72 hours before surgical incision.

The primary outcome was postoperative pain intensity assessed using the Numeric Rating Scale (NRS 0-10) at PACU arrival (T0) and at 30 (T1), 60 (T2), 90 (T3), and 120 (T4) minutes thereafter. Secondary outcomes included Verbal Rating Scale (VRS) scores, rescue morphine consumption (4 mg IV on request), and incidence of nausea/vomiting and hypersensitivity reactions. The primary longitudinal analysis used a linear mixed model with Group, Time, and Group×Time interaction as fixed effects and a random intercept per patient. Between-group contrasts at each timepoint were derived from estimated marginal means with Holm correction. Effect sizes are reported as Cohen's d.

The trial was approved by the institutional ethics and research committee (RPI #386-2024) and registered with the ISSSTE institutional research registry prior to enrolment. Due to institutional policy restrictions at the time of study initiation, registration on ClinicalTrials.gov was completed after data collection; this is disclosed transparently in accordance with CONSORT 2025 guidance on retrospective registration disclosure.

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Mexico
  • Mexico City
    • Mexico City, Mexico City, Mexico, 09360
      • Hospital Regional "General Ignacio Zaragoza," ISSSTE

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age 18-50 years
• ASA physical status I or II
• Body mass index between 18 and 35 kg/m²
• Scheduled for elective lower limb surgery under neuraxial anaesthesia
• Willing to provide written informed consent

Exclusion Criteria:

• Chronic use of analgesics or gabapentinoids
• Known hypersensitivity to tapentadol or pregabalin
• Pre-existing chronic pain

Elimination Criteria:

• Hypersensitivity reaction to any study drug during administration
• Hemodynamic shock of any etiology
• Requirement for advanced airway management or postoperative mechanical ventilation
• Surgical duration exceeding 120 minutes
• Requirement of an epidural catheter dose within the first two postoperative hours
• Voluntary withdrawal of consent at any point

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tapentadol; Oral tapentadol 50 mg every 12 hours for 72 hours before surgical incision (total daily dose 100 mg).	Drug: Tapentadol; Tapentadol 50 mg immediate-release oral tablet administered every 12 hours for 72 hours preoperatively (total of 6 doses).
Active Comparator: Pregabalin; Oral pregabalin 75 mg every 24 hours for 72 hours before surgical incision (total daily dose 75 mg).	Drug: Pregabalin; Pregabalin 75 mg oral capsule administered every 24 hours for 72 hours preoperatively (total of 3 doses).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain intensity by Numeric Rating Scale (NRS)	Postoperative pain intensity measured using the Numeric Rating Scale (NRS, 0-10; 0 = no pain, 10 = worst imaginable pain). The primary longitudinal analysis used a linear mixed model with Group, Time, and Group×Time interaction as fixed effects and a random intercept per patient. Between-group contrasts at each timepoint were derived from estimated marginal means with Holm correction. Effect sizes reported as Cohen's d.	At PACU arrival (T0), 30 minutes (T1), 60 minutes (T2), 90 minutes (T3), and 120 minutes (T4) post-arrival

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rescue morphine consumption	Proportion of patients requiring rescue analgesia (morphine 4 mg IV) and total morphine consumption (mg) in each group.	During the two-hour PACU observation period (T0-T4)
Incidence of nausea and vomiting	Proportion of patients experiencing nausea and/or vomiting in each group, assessed by clinical observation and patient report.	During the two-hour PACU observation period (T0-T4)
Hypersensitivity reactions	Incidence of any hypersensitivity or anaphylactic reaction to tapentadol or pregabalin, classified according to Müller criteria.	From first dose of study medication through 24 hours post-surgery
Verbal Rating Scale (VRS) pain category	Pain severity categorised as absence, low, moderate, or severe using the Verbal Rating Scale (VRS). Reported as proportions of patients in each category at each timepoint.	At PACU arrival (T0), 30 minutes (T1), 60 minutes (T2), 90 minutes (T3), and 120 minutes (T4) post-arrival

Collaborators and Investigators

• Sponsor: ISSSTE Hospital Regional "Gral. Ignacio Zaragoza"

Study record dates

Study Major Dates

• Study Start (Actual): June 19, 2024
• Primary Completion (Actual): July 3, 2024
• Study Completion (Actual): July 5, 2024

Study Registration Dates

• First Submitted: May 8, 2026
• First Submitted That Met QC Criteria: May 8, 2026
• First Posted (Actual): May 14, 2026

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Pregabalin; Acute postoperative pain; Tapentadol; Neuraxial anesthesia; Preemptive analgesia; Pilot randomized controlled trial; Lower limb surgery
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain, Postoperative; Amino Acids, Peptides, and Proteins; Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Acids, Acyclic; Carboxylic Acids; Hydrocarbons, Aromatic; Amino Acids; Phenols; Benzene Derivatives; gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Pregabalin; Tapentadol
• Other Study ID Numbers: ISSSTE RPI #386-2024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data underlying the results reported in this article, along with the full analysis code, will be made available following article publication via the corresponding author's public GitHub repository (https://github.com/phabel-LD).
• IPD Sharing Time Frame: Beginning at the time of article publication, with no end date.
• IPD Sharing Access Criteria: Data and code will be publicly available with no access restrictions via GitHub.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ANALYTIC_CODE; CSR

Drug and device information, study documents

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