Gabapentin Regimens and Their Effects on Opioid Consumption

NCT03334903 | Completed Phase 4 Results FDA Drug

• 1 other identifier: OpioidNeurontinTKR
• Study Type: interventional
• Target: 77
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the best strategy of administering gabapentin in connection with our current approach to perioperative pain management. We aim to evaluate two different adjunct gabapentin regimens given in the perioperative period, and to identify which manages patient pain more effectively and safely. In this evaluation, we will identify the quantity of patients' opioid consumption, the quality of their pain management, and the frequency and severity of any side effects they might experience. Patients who are undergoing total knee replacement (TKR) and choose to participate will be randomly assigned to a treatment group using computer-generated randomization. Patients in group 1 (the control group) will receive the standard of care as pertains to gabapentin. This consists of a single 600 mg dose of gabapentin administered to the patient approximately one to two hours before surgery, then a dose of 600 mg each morning during postoperative admission. Patients in Group 2 will receive 600 mg preoperatively, plus an additional postoperative gabapentin regimen: they will take 300 mg of gabapentin every 8 hours for 1 week, then a single nightly dose of 300 mg for another month.

Conditions

Knee Osteoarthritis; Knee Pain Chronic; Opioid Use; Opioid Dependence

Keywords

Total Knee Arthroplasty; Neurontin; Gabapentin; Opioid Tapering

Outcome Measures

Primary Outcomes (1)

• Opioid Consumption

  Mean opioid consumption, measured in mg of morphine equivalents.

  2-3 months following surgery (total amount measured at second postoperative appointment; means assessed afterwards).

Secondary Outcomes (6)

• Days Taking Opioids

  2-3 months following surgery (measured at second postoperative appointment).

• VAS Score 1: "How Much Pain do You Feel in Your Operative Site When Resting?"

  2-3 months after surgery (at 2nd postoperative appointment)

• VAS Score 2: "How Much Pain do You Feel in Your Operative Site When Moving?"

  2-3 months following surgery (measured at second postoperative appointment).

• VAS Score 3: "How Well Are You Sleeping?"

  2-3 months following surgery (measured at second postoperative appointment).

• VAS Score 4: "How Bad is Your Nausea?"

  2-3 months following surgery (measured at second postoperative appointment).

Study Arms (2)

Standard of Care

NO INTERVENTION

Standard of care includes one dose of 600 mg gabapentin in the immediate preoperative period (1-2 hours before surgery), then a dose of 600 mg each morning during postoperative admission.

Postoperative Gabapentin Regimen

EXPERIMENTAL

Single preoperative dose of 600 mg, as described above, plus an additional postoperative regimen. Patients will take 300 mg gabapentin every 8 hours for 1 week after discharge, then a single nightly dose of 300 mg gabapentin for another month.

Drug: Gabapentin

Interventions

Gabapentin DRUG

600 mg gabapentin before and after surgery. 300 mg gabapentin for approx. 5 weeks after surgery.

Also known as: Neurontin

Postoperative Gabapentin Regimen

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At least 18 years of age
• Receiving surgery for total knee replacement (TKR)
• Opioid naïve
• Agrees to use tracking diary to monitor opioid consumption

You may not qualify if:

• Over 75 years of age on the date of surgery
• If female, pregnant
• Has received investigational articles \< 30 days prior to enrollment or is currently receiving investigational products or devices
• Chronic pain syndrome
• Taking chronic narcotics and/or taking more than 10 mg of codeine per day, any amount of Hydrocodone, over 200 mg of tramadol per day, or any other narcotics prescribed for moderate or severe pain
• Involved in pain clinics for chronic pain, or pain that is not related to the surgical site
• On long-term gabapentin regimen
• Taking Lyrica or Gralise
• Known history of depression or has been treated for depression with medication
• Has entertained suicidal thoughts and behaviors

Sponsors & Collaborators

• Brigham and Women's Hospital: lead

Study Sites (1)

Brigham and Women's Faulkner Hospital

Boston, Massachusetts, 02130, United States

Location

Related Publications (25)

• Bannister K, Qu C, Navratilova E, Oyarzo J, Xie JY, King T, Dickenson AH, Porreca F. Multiple sites and actions of gabapentin-induced relief of ongoing experimental neuropathic pain. Pain. 2017 Dec;158(12):2386-2395. doi: 10.1097/j.pain.0000000000001040.

  PMID: 28832395 BACKGROUND

• Ozgencil E, Yalcin S, Tuna H, Yorukoglu D, Kecik Y. Perioperative administration of gabapentin 1,200 mg day-1 and pregabalin 300 mg day-1 for pain following lumbar laminectomy and discectomy: a randomised, double-blinded, placebo-controlled study. Singapore Med J. 2011 Dec;52(12):883-9.

  PMID: 22159931 BACKGROUND

• Rusy LM, Hainsworth KR, Nelson TJ, Czarnecki ML, Tassone JC, Thometz JG, Lyon RM, Berens RJ, Weisman SJ. Gabapentin use in pediatric spinal fusion patients: a randomized, double-blind, controlled trial. Anesth Analg. 2010 May 1;110(5):1393-8. doi: 10.1213/ANE.0b013e3181d41dc2.

  PMID: 20418301 BACKGROUND

• Stock CJ, Carpenter L, Ying J, Greene T. Gabapentin versus chlordiazepoxide for outpatient alcohol detoxification treatment. Ann Pharmacother. 2013 Jul-Aug;47(7-8):961-9. doi: 10.1345/aph.1R751. Epub 2013 Jun 18.

  PMID: 23780805 BACKGROUND

• Mason BJ, Quello S, Goodell V, Shadan F, Kyle M, Begovic A. Gabapentin treatment for alcohol dependence: a randomized clinical trial. JAMA Intern Med. 2014 Jan;174(1):70-7. doi: 10.1001/jamainternmed.2013.11950.

  PMID: 24190578 BACKGROUND

• Leung JG, Hall-Flavin D, Nelson S, Schmidt KA, Schak KM. The role of gabapentin in the management of alcohol withdrawal and dependence. Ann Pharmacother. 2015 Aug;49(8):897-906. doi: 10.1177/1060028015585849. Epub 2015 May 12.

  PMID: 25969570 BACKGROUND

• Grant MC, Lee H, Page AJ, Hobson D, Wick E, Wu CL. The Effect of Preoperative Gabapentin on Postoperative Nausea and Vomiting: A Meta-Analysis. Anesth Analg. 2016 Apr;122(4):976-85. doi: 10.1213/ANE.0000000000001120.

  PMID: 26991615 BACKGROUND

• Misra S, Parthasarathi G, Vilanilam GC. The effect of gabapentin premedication on postoperative nausea, vomiting, and pain in patients on preoperative dexamethasone undergoing craniotomy for intracranial tumors. J Neurosurg Anesthesiol. 2013 Oct;25(4):386-91. doi: 10.1097/ANA.0b013e31829327eb.

  PMID: 23603887 BACKGROUND

• Montazeri K, Kashefi P, Honarmand A. Pre-emptive gabapentin significantly reduces postoperative pain and morphine demand following lower extremity orthopaedic surgery. Singapore Med J. 2007 Aug;48(8):748-51.

  PMID: 17657384 BACKGROUND

• Rai AS, Khan JS, Dhaliwal J, Busse JW, Choi S, Devereaux PJ, Clarke H. Preoperative pregabalin or gabapentin for acute and chronic postoperative pain among patients undergoing breast cancer surgery: A systematic review and meta-analysis of randomized controlled trials. J Plast Reconstr Aesthet Surg. 2017 Oct;70(10):1317-1328. doi: 10.1016/j.bjps.2017.05.054. Epub 2017 Jun 9.

  PMID: 28751024 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

• Hassani V, Pazouki A, Nikoubakht N, Chaichian S, Sayarifard A, Shakib Khankandi A. The effect of gabapentin on reducing pain after laparoscopic gastric bypass surgery in patients with morbid obesity: a randomized clinical trial. Anesth Pain Med. 2015 Feb 1;5(1):e22372. doi: 10.5812/aapm.22372. eCollection 2015 Feb.

  PMID: 25789237 BACKGROUND

• Mardani-Kivi M, Mobarakeh MK, Keyhani S, Motlagh KH, Ekhtiari KS. Is gabapentin effective on pain management after arthroscopic anterior cruciate ligament reconstruction? A triple blinded randomized controlled trial. Arch Bone Jt Surg. 2013 Sep;1(1):18-22. Epub 2013 Sep 15.

  PMID: 25207278 BACKGROUND

• Chiu TW, Leung CC, Lau EY, Burd A. Analgesic effects of preoperative gabapentin after tongue reconstruction with the anterolateral thigh flap. Hong Kong Med J. 2012 Feb;18(1):30-4.

  PMID: 22302908 BACKGROUND

• Moore A, Costello J, Wieczorek P, Shah V, Taddio A, Carvalho JC. Gabapentin improves postcesarean delivery pain management: a randomized, placebo-controlled trial. Anesth Analg. 2011 Jan;112(1):167-73. doi: 10.1213/ANE.0b013e3181fdf5ee. Epub 2010 Nov 16.

  PMID: 21081764 BACKGROUND

• Menda F, Koner O, Sayin M, Ergenoglu M, Kucukaksu S, Aykac B. Effects of single-dose gabapentin on postoperative pain and morphine consumption after cardiac surgery. J Cardiothorac Vasc Anesth. 2010 Oct;24(5):808-13. doi: 10.1053/j.jvca.2009.10.023. Epub 2010 Jan 6.

  PMID: 20056448 BACKGROUND

• Ture H, Sayin M, Karlikaya G, Bingol CA, Aykac B, Ture U. The analgesic effect of gabapentin as a prophylactic anticonvulsant drug on postcraniotomy pain: a prospective randomized study. Anesth Analg. 2009 Nov;109(5):1625-31. doi: 10.1213/ane.0b013e3181b0f18b. Epub 2009 Aug 27.

  PMID: 19713257 BACKGROUND

• Clivatti J, Sakata RK, Issy AM. Review of the use of gabapentin in the control of postoperative pain. Rev Bras Anestesiol. 2009 Jan-Feb;59(1):87-98. doi: 10.1590/s0034-70942009000100012. English, Portuguese.

  PMID: 19374220 BACKGROUND

• Pandey CK, Navkar DV, Giri PJ, Raza M, Behari S, Singh RB, Singh U, Singh PK. Evaluation of the optimal preemptive dose of gabapentin for postoperative pain relief after lumbar diskectomy: a randomized, double-blind, placebo-controlled study. J Neurosurg Anesthesiol. 2005 Apr;17(2):65-8. doi: 10.1097/01.ana.0000151407.62650.51.

  PMID: 15840990 BACKGROUND

• Dierking G, Duedahl TH, Rasmussen ML, Fomsgaard JS, Moiniche S, Romsing J, Dahl JB. Effects of gabapentin on postoperative morphine consumption and pain after abdominal hysterectomy: a randomized, double-blind trial. Acta Anaesthesiol Scand. 2004 Mar;48(3):322-7. doi: 10.1111/j.0001-5172.2004.0329.x.

  PMID: 14982565 BACKGROUND

• Ho KY, Gan TJ, Habib AS. Gabapentin and postoperative pain--a systematic review of randomized controlled trials. Pain. 2006 Dec 15;126(1-3):91-101. doi: 10.1016/j.pain.2006.06.018. Epub 2006 Jul 18.

  PMID: 16846695 BACKGROUND

• Ucak A, Onan B, Sen H, Selcuk I, Turan A, Yilmaz AT. The effects of gabapentin on acute and chronic postoperative pain after coronary artery bypass graft surgery. J Cardiothorac Vasc Anesth. 2011 Oct;25(5):824-9. doi: 10.1053/j.jvca.2010.11.017. Epub 2011 Jan 12.

  PMID: 21232979 BACKGROUND

• Clarke H, Pereira S, Kennedy D, Gilron I, Katz J, Gollish J, Kay J. Gabapentin decreases morphine consumption and improves functional recovery following total knee arthroplasty. Pain Res Manag. 2009 May-Jun;14(3):217-22. doi: 10.1155/2009/930609.

  PMID: 19547761 BACKGROUND

• Smith RV, Havens JR, Walsh SL. Gabapentin misuse, abuse and diversion: a systematic review. Addiction. 2016 Jul;111(7):1160-74. doi: 10.1111/add.13324. Epub 2016 Mar 18.

  PMID: 27265421 BACKGROUND

• Menigaux C, Adam F, Guignard B, Sessler DI, Chauvin M. Preoperative gabapentin decreases anxiety and improves early functional recovery from knee surgery. Anesth Analg. 2005 May;100(5):1394-1399. doi: 10.1213/01.ANE.0000152010.74739.B8.

  PMID: 15845693 BACKGROUND

MeSH Terms

Conditions

Osteoarthritis, Knee; Opioid-Related Disorders

Interventions

Gabapentin

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. Wolfgang Fitz
• Organization: Brigham and Women's Hospital

wfitz@bwh.harvard.edu

6177325500

Study Officials

• Wolfgang Fitz, M.D.

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: Associate Orthopedic Surgeon

Model Details: Two-arm parallel design.

Study Record Dates

• First Submitted: November 3, 2017
• First Posted: November 7, 2017
• Study Start: May 15, 2018
• Primary Completion: April 24, 2019
• Study Completion: April 24, 2019
• Last Updated: February 18, 2021
• Results First Posted: February 18, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)