Preoperative Etanercept Before Inguinal Hernia Surgery

A Randomized Controlled Study Evaluating Pre-operative Etanercept on the Severity of Postoperative Pain After Inguinal Hernia Surgery.

Inguinal hernia repair is one of the most frequently performed operations in young men. Persistent pain after inguinal surgery represents a significant cause of disability, occurring in between 15%-35% of cases. In a majority of these patients, their groin pain persisted after a previous hernia repair. The main type of chronic postsurgical pain is neuropathic, caused by injured nerves. One of the principal components in the pathophysiology of postsurgical pain is cytokines, specifically tumor necrosis factor (TNF). In animal studies, injecting TNF inhibitors before nerve injury can reduce pain behaviors and neuropathology. Finding a way to reduce the incidence of postsurgical pain after hernia repair could enhance function, and reduce the need for opioids and other analgesics. The investigators intend to conduct the first randomized, controlled study evaluating whether preemptive administration of a tumor necrosis inhibitor can reduce postoperative pain and opioid consumption after hernia repair. This is important because the degree and intensity of postsurgical pain is a major predictor for the development of chronic postsurgical pain.

Study Overview

• Status: Completed
• Conditions: Postoperative Pain; Inguinal Hernia
• Intervention / Treatment: Drug: Etanercept; Drug: Saline

Detailed Description

76 patients with an inguinal hernia scheduled for surgical repair will be randomized in a 1:1 ratio to receive either subcutaneous etanercept or saline before skin incision. The study will be double-blind (i.e. neither the surgeon, anesthesiologist, nor the person administering the injection will know which group they were assigned to). Group I will receive 50 mg of subcutaneous etanercept mixed in 1 ml sterile water 90-120" before skin incision. Group II will receive 1 ml of sterile water 90-120" before skin incision. The anesthesia and surgical procedures will be standardized. For the next 24 hours, patients will keep a q4 hour pain diary recording their average pain on a 0-10 numerical rating scale. They will also record the number of Percocet tablets they took. All patients will be seen 1 month after their surgery, where their average pain score, work status, and analgesic intake (if any) will be recorded. Patients will then be followed with a telephone follow-up 3, 6 and 12-months post-procedure, where the same variables will be recorded.

• Study Type: Interventional
• Enrollment (Actual): 77
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, D.C., District of Columbia, United States, 20307
      • Walter Reed Army Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Demonstrable hernia evident using ultrasound, computed tomography, or on physical exam.
2. Pt scheduled for unilateral inguinal hernia repair.
3. Symptoms present for < 6 months.

Exclusion Criteria:

1. Non-elective surgery.
2. Previous hernia repair at the same site, or surgery near the site of the hernia.
3. Demyelinating neurological disease.
4. Current or recent (< 6 years) history of substance abuse.
5. Pregnancy, which will be ruled out by a urine pregnancy test in women of childbearing age.
6. Pre-existing untreated psychiatric condition that could preclude an optimal treatment response (e.g. untreated posttraumatic stress disorder).
7. Unstable medical condition (e.g. unstable angina or congestive heart failure or severe).
8. Rheumatoid arthritis, or other systemic conditions that might respond to TNF inhibitors.
9. Pt is immunosuppressed or is taking other drugs (e.g. corticosteroids) that might suppress the immune system.
10. Systemic infection.
11. Any opioid analgesics within 48 hours of skin incision.
12. Any use of tricyclic antidepressants, serotoninin-norepinephrine reuptake inhibitors, or anticonvulsants within 72 hours of skin incision.

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: 1; Etanercept 50 mg preoperatively	Drug: Etanercept; 50 mg subcutaenous preoperatively
Placebo Comparator: 2; Subcutaneous saline preoperatively	Drug: Saline; Given subcutaneously preoperatively

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Numerical Rating Scale Pain Score	0-10 pain score through 24-hours post-surgery. 0 is no pain and 10 is the worse pain imaginable. The primary outcome reported measure is the average of 4 scores, each comprised of 6-hour time intervals during the 24hour period.	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Analgesic Usage	Number of oxycodone/ acetaminophen tablets consumed through 24 hours post-surgery	24 hours
Chronic Post-surgical Pain	Patients with persistent post-surgical pain	Up to 12 months

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: Walter Reed Army Medical Center; John P. Murtha Neuroscience and Pain Institute
• Investigators: Study Chair: Scott Rehrig, MD, Walter Reed Army Medical Center

Publications and helpful links

General Publications

• Cheek CM, Black NA, Devlin HB, Kingsnorth AN, Taylor RS, Watkin DF. Groin hernia surgery: a systematic review. Ann R Coll Surg Engl. 1998;80 Suppl 1:S1-80.
• Franneby U, Sandblom G, Nordin P, Nyren O, Gunnarsson U. Risk factors for long-term pain after hernia surgery. Ann Surg. 2006 Aug;244(2):212-9. doi: 10.1097/01.sla.0000218081.53940.01.
• Ferzli GS, Edwards E, Al-Khoury G, Hardin R. Postherniorrhaphy groin pain and how to avoid it. Surg Clin North Am. 2008 Feb;88(1):203-16, x-xi. doi: 10.1016/j.suc.2007.10.006.
• Sommer C, Kress M. Recent findings on how proinflammatory cytokines cause pain: peripheral mechanisms in inflammatory and neuropathic hyperalgesia. Neurosci Lett. 2004 May 6;361(1-3):184-7. doi: 10.1016/j.neulet.2003.12.007.

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (Actual): November 1, 2011
• Study Completion (Actual): August 1, 2012

Study Registration Dates

• First Submitted: January 20, 2009
• First Submitted That Met QC Criteria: January 20, 2009
• First Posted (Estimate): January 21, 2009

Study Record Updates

• Last Update Posted (Actual): October 5, 2017
• Last Update Submitted That Met QC Criteria: September 6, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: preemptive analgesia; chronic postsurgical pain; postoperative pain; cytokine; inguinal hernia; patients with inguinal hernia scheduled for surgery
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pathological Conditions, Anatomical; Hernia, Abdominal; Pain, Postoperative; Hernia; Hernia, Inguinal; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Gastrointestinal Agents; Etanercept
• Other Study ID Numbers: WU08-6987