Preoperative Gabapentin vs Placebo for Vaginal Prolapse Surgery

Pelvic Organ Prolapse Clinical Trial

Official title:

A Double-Blind Randomized Placebo-Controlled Clinical Trial of Preoperative Gabapentin Prior to Vaginal Apical Suspension Prolapse Procedures

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT05658887
• Other study ID #: 202207210
• Status: Enrolling by invitation
• Phase: Phase 4
• Start date: January 1, 2023
• Est. completion date: December 31, 2024

Study information

• Verified date: May 2023
• Source: University of Iowa
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will recruit women scheduled to undergo vaginal apical suspension surgery (either uterosacral ligament suspension or sacrospinous ligament fixation) with or without other prolapse or anti-incontinence procedures. Participants will be randomized 1:1 to preoperative gabapentin or preoperative placebo (both patients and investigators will be blinded). Note the control group will receive preoperative acetaminophen/celecoxib/placebo and the treatment group will receive preoperative acetaminophen/celecoxib/gabapentin (preoperative acetaminophen/celecoxib are part of our current ERAS protocol). The primary outcome will be postoperative opioid use in the first 24 hours postoperatively measured in morphine milligram equivalents.

Description:

Enhanced Recovery after Surgery (ERAS) is an approach to perioperative care that focuses on evidence-based care protocols that emphasize minimizing stress and improving the body's response to stress. These protocols have resulted in a significant decrease in length of stay, complications, and cost in many different surgical specialities. Many of these protocols (including our current gynecology ERAS protocol) include preoperative gabapentin as an intervention to help reduce postoperative pain and postoperative opioid use. Gabapentin is an anticonvulsant medication that is commonly used for chronic neuropathic pain and other chronic pain disorders. The data regarding perioperative use of gabapentin is currently mixed, and the data in gynecology (and especially urogynecology) is limited. Notably gabapentin has been shown to be associated with sedation, respiratory depression, dizziness, and visual disturbances. In 2019, the U.S. Food and Drug Administration issued a warning that serious breathing difficulties may occur in patients using gabapentin with respiratory risk factors. Pelvic organ prolapse is a common benign condition, and surgery for pelvic organ prolapse is very common. Vaginal apical suspension is one of the most common surgeries for pelvic organ prolapse. There is very limited data on the utility of preoperative gabapentin for vaginal apical suspension surgery. This study will recruit women scheduled to undergo vaginal apical suspension surgery (either uterosacral ligament suspension or sacrospinous ligament fixation) with or without other prolapse or anti-incontinence procedures. Participants will be randomized 1:1 to preoperative gabapentin or preoperative placebo (both patients and investigators will be blinded). Note the control group will receive preoperative acetaminophen/celecoxib/placebo and the treatment group will receive preoperative acetaminophen/celecoxib/gabapentin (preoperative acetaminophen/celecoxib are part of our current ERAS protocol). The primary outcome will be postoperative opioid use in the first 24 hours postoperatively measured in morphine milligram equivalents.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 110
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Scheduled for a vaginal apical support procedure (sacrospinous ligament fixation or vaginal uterosacral ligament suspension)
• Female
• Age 18 or higher

Exclusion Criteria:

• Non-English speaking
• Incarcerated
• Cognitive impairment precluding informed consent
• Chronic opioid user
• Chronic gabapentinoid user
• Contraindication to acetaminophen, celecoxib, or gabapentinoids
• Concurrent laparoscopic or abdominal surgery

Related Conditions & MeSH terms

• Pelvic Organ Prolapse
• Perioperative/Postoperative Complications
• Postoperative Complications
• Prolapse

Intervention

Drug:
• Gabapentin
One dose of preoperative gabapentin 300 mg prior to vaginal apical support procedure
• Gabapentin Placebo
Gabapentin Placebo

Locations

Country	Name	City	State
United States	University of Iowa	Iowa City	Iowa

Sponsors (2)

Lead Sponsor	Collaborator
Joseph Kowalski	University of Iowa

Country where clinical trial is conducted

United States, 

References & Publications (20)

Altman AD, Robert M, Armbrust R, Fawcett WJ, Nihira M, Jones CN, Tamussino K, Sehouli J, Dowdy SC, Nelson G. Guidelines for vulvar and vaginal surgery: Enhanced Recovery After Surgery Society recommendations. Am J Obstet Gynecol. 2020 Oct;223(4):475-485. doi: 10.1016/j.ajog.2020.07.039. Epub 2020 Jul 24. — View Citation

Bolliger M, Kroehnert JA, Molineus F, Kandioler D, Schindl M, Riss P. Experiences with the standardized classification of surgical complications (Clavien-Dindo) in general surgery patients. Eur Surg. 2018;50(6):256-261. doi: 10.1007/s10353-018-0551-z. Epub 2018 Jul 24. — View Citation

Committee Opinion No. 750: Perioperative Pathways: Enhanced Recovery After Surgery: Correction. Obstet Gynecol. 2019 Nov;134(5):1121. doi: 10.1097/AOG.0000000000003569. No abstract available. — View Citation

Doleman B, Heinink TP, Read DJ, Faleiro RJ, Lund JN, Williams JP. A systematic review and meta-regression analysis of prophylactic gabapentin for postoperative pain. Anaesthesia. 2015 Oct;70(10):1186-204. doi: 10.1111/anae.13179. Epub 2015 Aug 24. — View Citation

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. Erratum In: JAMA Surg. 2018 Apr 1;153(4):396. JAMA Surg. 2022 Jun 1;157(6):553. — View Citation

Huynh TQ, Patel NR, Goldstein ND, Makai GE. Preoperative Gabapentin for Minimally Invasive Hysterectomy: A Randomized Controlled Trial. J Minim Invasive Gynecol. 2021 Feb;28(2):237-244.e2. doi: 10.1016/j.jmig.2020.04.040. Epub 2020 May 8. — View Citation

Karcioglu O, Topacoglu H, Dikme O, Dikme O. A systematic review of the pain scales in adults: Which to use? Am J Emerg Med. 2018 Apr;36(4):707-714. doi: 10.1016/j.ajem.2018.01.008. Epub 2018 Jan 6. — View Citation

Li ALK, Wadsworth K, Siddiqui NT, Alarab M, McDermott CD, Lemos N, Dawood A, Lovatsis D. Does low-dose gapapentin reduce opioid use postoperatively?: A randomized controlled trial in women undergoing reconstructive pelvic surgery. Int Urogynecol J. 2019 Feb;30(2):211-217. doi: 10.1007/s00192-018-3617-3. Epub 2018 Mar 21. — View Citation

Ljungqvist O, Scott M, Fearon KC. Enhanced Recovery After Surgery: A Review. JAMA Surg. 2017 Mar 1;152(3):292-298. doi: 10.1001/jamasurg.2016.4952. — View Citation

Mathieson S, Lin CC, Underwood M, Eldabe S. Pregabalin and gabapentin for pain. BMJ. 2020 Apr 28;369:m1315. doi: 10.1136/bmj.m1315. No abstract available. — View Citation

Mehr AA, Elmer-Lyon C, Maetzold E, Bradley CS, Kowalski JT. Effect of Enhanced Recovery Protocol on Opioid Use in Pelvic Organ Prolapse Surgery. Female Pelvic Med Reconstr Surg. 2021 Dec 1;27(12):e705-e709. doi: 10.1097/SPV.0000000000001114. — View Citation

Nelson G, Bakkum-Gamez J, Kalogera E, Glaser G, Altman A, Meyer LA, Taylor JS, Iniesta M, Lasala J, Mena G, Scott M, Gillis C, Elias K, Wijk L, Huang J, Nygren J, Ljungqvist O, Ramirez PT, Dowdy SC. Guidelines for perioperative care in gynecologic/oncology: Enhanced Recovery After Surgery (ERAS) Society recommendations-2019 update. Int J Gynecol Cancer. 2019 May;29(4):651-668. doi: 10.1136/ijgc-2019-000356. Epub 2019 Mar 15. — View Citation

Pelvic Organ Prolapse: ACOG Practice Bulletin, Number 214. Obstet Gynecol. 2019 Nov;134(5):e126-e142. doi: 10.1097/AOG.0000000000003519. — View Citation

Rorarius MG, Mennander S, Suominen P, Rintala S, Puura A, Pirhonen R, Salmelin R, Haanpaa M, Kujansuu E, Yli-Hankala A. Gabapentin for the prevention of postoperative pain after vaginal hysterectomy. Pain. 2004 Jul;110(1-2):175-81. doi: 10.1016/j.pain.2004.03.023. — View Citation

Sammarco AG, Swenson CW, Kamdar NS, Kobernik EK, DeLancey JOL, Nallamothu B, Morgan DM. Rate of Pelvic Organ Prolapse Surgery Among Privately Insured Women in the United States, 2010-2013. Obstet Gynecol. 2018 Mar;131(3):484-492. doi: 10.1097/AOG.0000000000002485. — View Citation

Scheib SA, Thomassee M, Kenner JL. Enhanced Recovery after Surgery in Gynecology: A Review of the Literature. J Minim Invasive Gynecol. 2019 Feb;26(2):327-343. doi: 10.1016/j.jmig.2018.12.010. Epub 2018 Dec 20. — View Citation

Smith TW Jr, Wang X, Singer MA, Godellas CV, Vaince FT. Enhanced recovery after surgery: A clinical review of implementation across multiple surgical subspecialties. Am J Surg. 2020 Mar;219(3):530-534. doi: 10.1016/j.amjsurg.2019.11.009. Epub 2019 Nov 16. — View Citation

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. Erratum In: Anesthesiology. 2020 Aug 21;:null. — View Citation

Weingarten TN, Jacob AK, Njathi CW, Wilson GA, Sprung J. Multimodal Analgesic Protocol and Postanesthesia Respiratory Depression During Phase I Recovery After Total Joint Arthroplasty. Reg Anesth Pain Med. 2015 Jul-Aug;40(4):330-6. doi: 10.1097/AAP.0000000000000257. — View Citation

Zhong B. How to calculate sample size in randomized controlled trial? J Thorac Dis. 2009 Dec;1(1):51-4. — View Citation

* Note: There are 20 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Postoperative opioid use	Total postoperative opioid use in the first 24 hours postop measured in MME (starting when the patient leaves the operating room)	24 hours after surgery
Secondary	Mean postoperative pain score	Mean postoperative pain score (using the validated numerical rating scale, minimum score 0, maximum score 10, higher scores mean worse pain/worse outcome) while admitted	After surgery, max of 24 hours
Secondary	postoperative opioid use	postoperative opioid use while admitted	After surgery, max of 24 hours
Secondary	Time to discharge	Time (in hours) to discharge after surgery	After surgery, at the time the patient is discharged
Secondary	Anti-emetic use	Postoperative anti-emetic use	After surgery, max of 24 hours
Secondary	Number of patients that had an adverse event	Adverse events	After surgery until 24 hours postoperative
Secondary	Number of patients who report postoperative dizziness	Patient reported postoperative dizziness	24 hours postoperative
Secondary	Number of patients who report sedation	Patient reported sedation	24 hours postoperative
Secondary	Number of patients who report visual changes	Patient reported visual changes	24 hours postoperative
Secondary	Number of patients who report postoperative nausea and vomiting	Patient reported postoperative nausea and vomiting	24 hours postoperative
Secondary	Number of patients who report postoperative pain adequacy	Patient reported postoperative pain adequacy	24 hours postoperative