Pregabalin vs. Gabapentin on Reducing Opioid Usage

NCT04705480 | Completed Phase 4 Results FDA Drug

• 1 other identifier: 20-718
• Study Type: interventional
• Target: 109
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center, randomized, open-label, Phase 4 clinical trial investigating the efficacy of multiple-dose administrations of Pregabalin or Gabapentin in combination with traditional opioid pain medications to decrease the amount of opioid pain medication usage in single-system orthopedic trauma patients.

Conditions

Analgesics; Gabapentin; Injuries; Narcotics; Pain; Trauma

Keywords

Pregabalin , ,; Gabapentin; Opioid Pain Medication Use; Trauma; Opioid Usage Reduction

Outcome Measures

Primary Outcomes (1)

• Reduction in Opioid Usage

  To determine if adding multiple doses of pregabalin or gabapentin upon admission will reduce opioid usage administered in oral Morphine Milligram Equivalents in trauma patients.

  First 7 days post-enrollment or until discharge, if discharge < 7 days post-enrollment

Secondary Outcomes (5)

• Difference in Initial and Last Incentive Spirometry Values

  Initial and last incentive spirometry, with an approximate duration of 7days or discharge; if discharge < 7 days post-enrollment.

• Rate of Intubation

  First 7 days post-enrollment or until discharge, if discharge < 7 days post-enrollment

• Pain Control

  First 7 days post-enrolment or until discharge, if discharge < 7 days post-enrollment

• Hospital Length of Stay

  First 7 days post-enrollment or until discharge, if discharge < 7 days post-enrollment

• Rate of Unplanned ICU Admission

  First 7 days post-enrollment or until discharge, if discharge < 7 days post-enrollment

Study Arms (3)

Pregabalin

EXPERIMENTAL

Patients will receive 50 mg every 8 hours without dose titration. Patients with CrCl \< 60mL/min will receive same dose given q12 hours. The q12 hour regimen may be increased to q8 hours if CrCl increases above 60mL/min during the 7 days study period or until discharge (if \< 7 days post-enrollment).

Drug: Pregabalin 50mg

Gabapentin

EXPERIMENTAL

Patients will receive 300 mg PO every 8 hours without dose titration. Patients with CrCl \< 60mL/min will receive same dose given q12 hours. The q12 hour regimen may be increased to q8 hours if CrCl increases above 60mL/min during the 7 days study period or until discharge (if \< 7 days post-enrollment).

Drug: Gabapentin 300mg

Neither Pregabalin nor Gabapentin

ACTIVE COMPARATOR

Patients will receive neither Pregabalin nor Gabapentin

Drug: Neither Pregabalin nor Gabapentin

Interventions

Neither Pregabalin nor Gabapentin DRUG

Patients will receive neither Pregabalin nor Gabapentin.

Neither Pregabalin nor Gabapentin

Pregabalin 50mg DRUG

Patients will receive 50 mg every 8 hours without dose titration. Patients with CrCl \< 60mL/min will receive same dose given q12 hours. The q12 hour regimen may be increased to q8 hours if CrCl increases above 60mL/min during the 7 days study period or until discharge (if \< 7 days post-enrollment).

Also known as: Lyrica

Pregabalin

Gabapentin 300mg DRUG

Patients will receive 300 mg PO every 8 hours without dose titration. Patients with CrCl \< 60mL/min will receive same dose given q12 hours. The q12 hour regimen may be increased to q8 hours if CrCl increases above 60mL/min during the 7 days study period or until discharge (if \< 7 days post-enrollment).

Also known as: Neurontin

Gabapentin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Nurse Practitioner service admissions
• years of age or older
• Patients enrolled within 36 hours of admission
• Anticipated duration of hospitalization \> 24 hours from time of consent
• Active order(s) for opioids in place at the time of enrollment

You may not qualify if:

• Clinician discretion based on patient care management
• Intubated patients
• Patients with epidural
• Patients with pregabalin/gabapentin as home medications
• Patients receiving pregabalin/gabapentin upon admission
• Traumatic brain injury patients
• CrCl\<30ml/min or on HD
• Unable to take enteral medications
• On Patient Controlled Analgesia (PCA)
• Patients with complicated wound closure
• History of epilepsy
• Documented history of substance use disorder

Sponsors & Collaborators

• West Virginia Clinical and Translational Science Institute: collaborator
• CAMC Health System: lead

Study Sites (1)

Charleston Area Medical Center"s Level 1 Trauma Center

Charleston, West Virginia, 25301, United States

Location

Related Publications (23)

• Fabbri A, Voza A, Riccardi A, Serra S, Iaco F; Study and Research Center of the Italian Society of Emergency Medicine (SIMEU). The Pain Management of Trauma Patients in the Emergency Department. J Clin Med. 2023 May 5;12(9):3289. doi: 10.3390/jcm12093289.

  PMID: 37176729 BACKGROUND

• Ling W, Mooney L, Hillhouse M. Prescription opioid abuse, pain and addiction: clinical issues and implications. Drug Alcohol Rev. 2011 May;30(3):300-5. doi: 10.1111/j.1465-3362.2010.00271.x.

  PMID: 21545561 BACKGROUND

• Florence C, Luo F, Rice K. The economic burden of opioid use disorder and fatal opioid overdose in the United States, 2017. Drug Alcohol Depend. 2021 Jan 1;218:108350. doi: 10.1016/j.drugalcdep.2020.108350. Epub 2020 Oct 27.

  PMID: 33121867 BACKGROUND

• Ramirez MF, Kamdar BB, Cata JP. Optimizing Perioperative Use of Opioids: A Multimodal Approach. Curr Anesthesiol Rep. 2020 Dec;10(4):404-415. doi: 10.1007/s40140-020-00413-6. Epub 2020 Sep 7.

  PMID: 33281504 BACKGROUND

• Simpson JC, Bao X, Agarwala A. Pain Management in Enhanced Recovery after Surgery (ERAS) Protocols. Clin Colon Rectal Surg. 2019 Mar;32(2):121-128. doi: 10.1055/s-0038-1676477. Epub 2019 Feb 28.

  PMID: 30833861 BACKGROUND

• Ahmadi A, Bazargan-Hejazi S, Heidari Zadie Z, Euasobhon P, Ketumarn P, Karbasfrushan A, Amini-Saman J, Mohammadi R. Pain management in trauma: A review study. J Inj Violence Res. 2016 Jul;8(2):89-98. doi: 10.5249/jivr.v8i2.707. Epub 2016 Jul 7.

  PMID: 27414816 BACKGROUND

• Tiippana EM, Hamunen K, Kontinen VK, Kalso E. Do surgical patients benefit from perioperative gabapentin/pregabalin? A systematic review of efficacy and safety. Anesth Analg. 2007 Jun;104(6):1545-56, table of contents. doi: 10.1213/01.ane.0000261517.27532.80.

  PMID: 17513656 BACKGROUND

• Chin KK, Carroll I, Desai K, Asch S, Seto T, McDonald KM, Curtin C, Hernandez-Boussard T. Integrating Adjuvant Analgesics into Perioperative Pain Practice: Results from an Academic Medical Center. Pain Med. 2020 Jan 1;21(1):161-170. doi: 10.1093/pm/pnz053.

  PMID: 30933284 BACKGROUND

• Arumugam S, Lau CS, Chamberlain RS. Use of preoperative gabapentin significantly reduces postoperative opioid consumption: a meta-analysis. J Pain Res. 2016 Sep 12;9:631-40. doi: 10.2147/JPR.S112626. eCollection 2016.

  PMID: 27672340 BACKGROUND

• Schulz KF, Altman DG, Moher D; CONSORT Group. CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. BMJ. 2010 Mar 23;340:c332. doi: 10.1136/bmj.c332.

  PMID: 20332509 BACKGROUND

• Hah J, Mackey SC, Schmidt P, McCue R, Humphreys K, Trafton J, Efron B, Clay D, Sharifzadeh Y, Ruchelli G, Goodman S, Huddleston J, Maloney WJ, Dirbas FM, Shrager J, Costouros JG, Curtin C, Carroll I. Effect of Perioperative Gabapentin on Postoperative Pain Resolution and Opioid Cessation in a Mixed Surgical Cohort: A Randomized Clinical Trial. JAMA Surg. 2018 Apr 1;153(4):303-311. doi: 10.1001/jamasurg.2017.4915.

  PMID: 29238824 BACKGROUND

• Campbell R, Khuong JN, Liu Z, Borg C, Jackson S, Ramson DM, Kok J, Douglas N, Penny-Dimri JC, Perry LA. Perioperative gabapentinoid use lowers short-term opioid consumption following lower limb arthroplasty: Systematic review and meta-analysis. J Opioid Manag. 2021 May-Jun;17(3):251-272. doi: 10.5055/jom.2021.0635.

  PMID: 34259336 BACKGROUND

• Markman J, Resnick M, Greenberg S, Katz N, Yang R, Scavone J, Whalen E, Gregorian G, Parsons B, Knapp L. Efficacy of pregabalin in post-traumatic peripheral neuropathic pain: a randomized, double-blind, placebo-controlled phase 3 trial. J Neurol. 2018 Dec;265(12):2815-2824. doi: 10.1007/s00415-018-9063-9. Epub 2018 Sep 21.

  PMID: 30242745 BACKGROUND

• Gordh TE, Stubhaug A, Jensen TS, Arner S, Biber B, Boivie J, Mannheimer C, Kalliomaki J, Kalso E. Gabapentin in traumatic nerve injury pain: a randomized, double-blind, placebo-controlled, cross-over, multi-center study. Pain. 2008 Aug 31;138(2):255-266. doi: 10.1016/j.pain.2007.12.011. Epub 2008 Feb 6.

  PMID: 18258368 BACKGROUND

• Moore RA, Straube S, Wiffen PJ, Derry S, McQuay HJ. Pregabalin for acute and chronic pain in adults. Cochrane Database Syst Rev. 2009 Jul 8;(3):CD007076. doi: 10.1002/14651858.CD007076.pub2.

  PMID: 19588419 BACKGROUND

• Bockbrader HN, Wesche D, Miller R, Chapel S, Janiczek N, Burger P. A comparison of the pharmacokinetics and pharmacodynamics of pregabalin and gabapentin. Clin Pharmacokinet. 2010 Oct;49(10):661-9. doi: 10.2165/11536200-000000000-00000.

  PMID: 20818832 BACKGROUND

• Evoy KE, Sadrameli S, Contreras J, Covvey JR, Peckham AM, Morrison MD. Abuse and Misuse of Pregabalin and Gabapentin: A Systematic Review Update. Drugs. 2021 Jan;81(1):125-156. doi: 10.1007/s40265-020-01432-7.

  PMID: 33215352 BACKGROUND

• Dalsgaard H, Kim Peder Dalhoff, Heerfordt IM. A review of the addictive potential of pregabalin and gabapentin. Adverse Drug React Bull. 2024;347(1):1347-1350. doi:https://doi.org/10.1097/fad.0000000000000076

  BACKGROUND

• Kuehn BM. Growing Role of Gabapentin in Opioid-Related Overdoses Highlights Misuse Potential and Off-label Prescribing Practices. JAMA. 2022 Oct 4;328(13):1283-1285. doi: 10.1001/jama.2022.13659.

  PMID: 36069924 BACKGROUND

• Hahn J, Jo Y, Yoo SH, Shin J, Yu YM, Ah YM. Risk of major adverse events associated with gabapentinoid and opioid combination therapy: A systematic review and meta-analysis. Front Pharmacol. 2022 Oct 11;13:1009950. doi: 10.3389/fphar.2022.1009950. eCollection 2022.

  PMID: 36304170 BACKGROUND

• Kharasch ED, Clark JD, Kheterpal S. Perioperative Gabapentinoids: Deflating the Bubble. Anesthesiology. 2020 Aug;133(2):251-254. doi: 10.1097/ALN.0000000000003394. No abstract available.

  PMID: 32667153 BACKGROUND

• Patel AS, Abrecht CR, Urman RD. Gabapentinoid Use in Perioperative Care and Current Controversies. Curr Pain Headache Rep. 2022 Feb;26(2):139-144. doi: 10.1007/s11916-022-01012-2. Epub 2022 Jan 27.

  PMID: 35084656 BACKGROUND

• Verret M, Lauzier F, Zarychanski R, Perron C, Savard X, Pinard AM, Leblanc G, Cossi MJ, Neveu X, Turgeon AF; Canadian Perioperative Anesthesia Clinical Trials (PACT) Group. Perioperative Use of Gabapentinoids for the Management of Postoperative Acute Pain: A Systematic Review and Meta-analysis. Anesthesiology. 2020 Aug;133(2):265-279. doi: 10.1097/ALN.0000000000003428.

  PMID: 32667154 BACKGROUND

Related Links

• Center for Disease Control and Prevention. Drug overdose mortality by state. Center for Disease Control and Prevention. Published 2022.
• Centers for Disease Control and Prevention. About Prescription Opioids. Overdose Prevention. Published May 8, 2024
• American College of Surgeons. ACS Trauma Quality Programs Best Practices Guidelines for Acute Pain Management in Trauma Patients.; 2020

MeSH Terms

Conditions

Wounds and Injuries; Pain

Interventions

Pregabalin; Gabapentin

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins; Amines; Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons

Limitations and Caveats

The estimated sample size was not attained due to organizational implementations of specified multi-modal regimens. The limited sample size may have rendered the study underpowered to detect significant effects and constrained the generalizability of the study findings. Inconsistences existed in gabapentinoids being initiated perioperative versus post-operatively. Pain scores were only collected at time of opioid medication requests not comprehensively.

Results Point of Contact

• Title: Nancy Duvall
• Organization: Charleston Area Medical Center

nancy.duvall@vandaliahealth.org

304-388-3653

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Investigator

Study Record Dates

• First Submitted: January 8, 2021
• First Posted: January 12, 2021
• Study Start: April 12, 2021
• Primary Completion: September 30, 2024
• Study Completion: December 13, 2024
• Last Updated: January 6, 2026
• Results First Posted: January 6, 2026

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)