Surgical Pain After Inguinal Hernia Repair (SPAIHR)

Study Overview
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Brief Summary
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The purpose of this study is to test whether pregabalin added to the standard of care with dosing starting preoperatively and continuing for 1 week post surgery will decrease the intensity of acute post-operative pain following inguinal hernia repair.

Official Title
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A Randomized, Double Blind Multi Center Dose Ranging Study Of The Efficacy And Safety Of Pregabalin Compared To Placebo In The Adjunctive Treatment Of Post Surgical Pain After Primary Inguinal Hernia Repair

Conditions
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Pain, Postoperative, Hernia, Inguinal

Intervention / Treatment
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* Drug: Pregabalin
* Drug: placebo
* Drug: Pregabalin
* Drug: Pregabalin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject will have elective ( the subject chooses, but does not have to undergo surgery for an emergency) open unilateral inguinal herniorraphy (hernia repair), using mesh Lichtenstein surgery procedure and under general anesthesia and fentanyl or sufentanil/propofol initiation and sevoflurane or isoflurane maintenance plus local anesthetic infiltration at the conclusion of surgery. Study surgery should be anticipated to be in the morning. Expected to be able to use and tolerate non-steroidal anti-inflammatory drugs (such as naproxen), tramadol, oxycodone, and acetaminophen/paracetamol for pain control after surgery. The subject will be available for a visit within 72 hours of the day of surgery if not admitted the night before for baseline assessments before taking any study medication, and then to receive study medication prior to the day before surgery. The subject is expected and agrees to remain at the hospital (or intermediate care facility) for a minimum of 3 hours following surgery. Exclusion Criteria: Subjects with non elective or emergency surgery (must have the surgery no matter what), or hernia with incarceration (the trapping of abdominal contents within the hernia itself). Subjects with hernia repair that is not a primary repair. The planned use of nerve block or spinal/epidural/paravertebral anesthesia or surgery is not planned with general anesthesia. Subjects that are not allowed to receive the anesthesia agents indicated per protocol and general anesthesia.

Ages Eligible for Study
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Minimum Age: 17 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 3<br> | Drug: Pregabalin<br>* 150 mg BID<br>|
| Placebo Comparator: 4<br> | Drug: placebo<br>* Placebo<br>|
| Experimental: 2<br> | Drug: Pregabalin<br>* 75 mg BID<br>|
| Experimental: 1<br> | Drug: Pregabalin<br>* 25 mg BID<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Modified Brief Pain Inventory-Short Form (mBPI-sf): Worst Pain 24 Hours Post Surgery | m-BPI-sf: a self-administered 11-point Likert rating scale to rate pain in the past 24 hours. A single item pertains to worst pain in the past 24 hours: range of 0 (no pain) to 10 (worst imaginable pain). | 24 hours post surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Numeric Rating Scale (NRS): Current Pain With Movement - Sitting | NRS: a self-administered questionnaire to rate pain. A single item asks to rate pain with movement caused by sitting (sitting in a standardized fashion after being in a fully supine position); range: 0 (no pain) to 10 (worst pain). | Baseline; 2 hours (h) before surgery (BS); 1, 2, and 3 h post surgery (PS); Days 2, 3, 4, 5, 6, and 7 PS; and End of Treatment (EOT [Day 7 PS or Early Termination]) | 
| Numeric Rating Scale (NRS): Current Pain With Movement - Walking | NRS: a self-administered questionnaire to rate pain. A single item asks to rate pain with movement caused by walking (rising from sitting position and walking approximately 5 meters or 16 feet at a moderate pace); range: 0 (no pain) to 10 (worst pain). | Baseline; 2 hours (h) before surgery (BS); 1, 2, and 3 h post surgery (PS); Days 2, 3, 4, 5, 6, and 7 PS; and End of Treatment (EOT [Day 7 PS or Early Termination]) | 
| Numeric Rating Scale (NRS): Current Pain With Movement - Coughing | NRS: a self-administered questionnaire to rate pain. A single item asks to rate pain with movement caused by coughing (coughing two times while sitting); range: 0 (no pain) to 10 (worst pain) | Baseline; 2 hours (h) before surgery (BS); 1, 2, and 3 h post surgery (PS); Days 2, 3, 4, 5, 6, and 7 PS; and End of Treatment (EOT [Day 7 PS or Early Termination]) | 
| Numeric Rating Scale (NRS): Current Pain With Movement - Area Under the Curve (AUC) for Sitting, Walking, and Coughing | NRS: a self-administered questionnaire to rate pain. AUC from 1 h PS through 48 h PS for ratings of pain caused by movements of sitting, walking, and coughing; Range: 0 (no pain) to 10 (worst pain). | 1 hour through 48 hours post surgery | 
| Numerical Rating Scale (NRS): Current Pain at Rest | NRS: a self-administered questionnaire to rate pain. A single item asks participant to rate current pain at rest (preceding pain with movement); range: 0 (no pain) to 10 (worst pain). | 2 hours (h) before surgery (BS); 1, 2, and 3 h post surgery (PS); Days 2, 3, 4, 5, 6, 7, 8, 9, and 10 PS | 
| Numeric Rating Scale (NRS): Current Pain at Rest - Area Under the Curve (AUC) | NRS: a self-administered questionnaire to rate pain. AUC for a single item asking participant to rate current pain at rest (preceding pain with movement); range: 0 (no pain) to 10 (worst pain). | 1 through 48 hours post surgery (PS) | 
| Numeric Rating Scale (NRS): Average Pain | NRS: a self-administered questionnaire to rate pain. A single item asks participant to rate pain on average in the last 24 hours; range: 0 (no pain) to 10 (worst pain). | 2 hours (h) before surgery (BS); 1, 2, and 3 h post surgery (PS); Days 1, 2, 3, 4, 5, 6, and 7 PS | 
| Time From End of Surgery to First Rescue Medication | Rescue medication includes both naproxen and narcotic medication (including tramadol and opioid analgesics). For subjects without use of rescue medication, the time-to-event variable is censored at the Beginning of Taper Visit (Day 7 PS) or at time of withdrawal. | Day 1 through Day 7 post surgery | 
| Time From End of Surgery to Reach a Total Score of at Least 9 on the Post-Anesthetic Discharge Scoring System (PADS) | PADS is a 5-item scale (individual item range: 0-2; higher scores indicating better readiness for hospital discharge). Total score range: 0-10, with 9 or higher indicating eligibility for discharge. End of surgery is time of transfer to post-anesthesia care unit (PACU). Subjects who did not reach a score of 9 on PADS were censored at the date and time of discharge. | Day 1 | 
| Time From End of Surgery to Discharge From Post-Anesthesia Care Unit (PACU) |  | Day 1 | 
| Daily Sleep Interference Rating Scale (DSIRS) Score | DSIRS: self-administered 11-point Likert scale ranging from 0 (pain does not interfere with sleep) to 10 (pain completely interferes with sleep [unable to sleep due to pain]) during past 24-hour period. Higher score indicates a greater level of sleep disturbance. Performed daily on awakening, prior to taking study medication. | Days 2, 3, 4, 5, 6, 7, 8, 9, and 10 post surgery (PS) | 
| Total Cumulative Dose of Opioids and Tramadol Used During and After Surgery | Total cumulative dose of opioids and tramadol administered by any route during surgery and postoperatively. Dose of tramadol calculated as milligrams (mg) of oral morphine equivalent. | 24, 48, and 72 hours (h) post surgery (PS), and Days 4, 5, 6, and 7 PS | 
| Amount of Non-opioid Rescue Medication (Naproxen and Antiemetic Medications) Used During the Study | Total cumulative dose of naproxen calculated in milligrams (mg) from the end of surgery up to and including Day 7 after surgery. | End of Surgery through Day 7 post surgery | 
| Total Clinically Meaningful Event (CME) Score and Cumulative Total Distinct CME Score Using the Opioid-Related Symptom Distress Scale (OR-SDS) | OR-SDS: a self-administered assessment of 10 common opioid-related side effects (symptoms). A CME is a severe or very severe symptom (or moderate or greater severity symptom of confusion). The Total Distinct CME score is the sum of CMEs across symptoms (range: 0 [none] to 10 [10 CMEs]); the Cumulative Total Distinct (CT Distinct) CME score is the sum of Total Distinct CME scores at observation and prior observations. The Total CME score is the same as the Total Distinct CME score except that only 1 CME is counted if both nausea and vomiting (or retching) occur (range: 0 [none] to 9 [9 CMEs]). | 3, 24, and 72 hours (h) Post-Surgery (PS), and End of Treatment (EOT [Day 7 PS or Early Termination]) | 
| Participants With Clinically Meaningful Events (CMEs) for Individual Symptoms Using the Opioid-Related Symptom Distress Scale (OR-SDS) | OR-SDS: a self-administered assessment of 10 common opioid-related side effects (symptoms). A CME is a severe or very severe symptom (or moderate or greater severity symptom of confusion). For individual symptom categories, the number of subjects who experienced at least one CME. Concentrate (concentr). | 3, 24, and 72 hours (h) post surgery (PS), and End of Treatment (EOT [Day 7 PS or Early Termination]) | 
| Subject Global Evaluation of Study Medication (GESM) | GESM is a self-administered overall impression (global evaluation) of study medication received for pain; 4 categories: poor, fair, good, and excellent. | 24 hours (h) post surgery (PS) and End of Treatment (EOT [Day 7 PS or Early Termination]) | 
| Participants With Wound Healing Complications | Investigator-assigned mutually exclusive categories of: 1) no surgical wound complication, 2) superficial incisional surgical site infection, 3) deep incisional surgical site infection, 4) organ or space surgical site infection, or 5) non-infectious wound healing complication. | Day 7 post surgery (PS) and up to 30 days PS | 
| Participants With Physician Contacts Post-discharge | Number of participants who answered yes to the Post-Surgery Contact question: From the time you were discharged from the hospital, did you have to contact any type of physician because of pain, difficulty getting up and walking about, or difficulty with passing urine? | 24 and 72 hours (h) post surgery (PS) | 
| Baseline and Change From Baseline in Anxiety Visual Analog Scale (VAS) Score | Anxiety VAS is a single-item self-administered continuous measure of anxiety using a 100-millimeter (mm) line on which the subject is asked to place a mark indicating the intensity of current anxiety. The score is the distance in mm from the left-most point on the line to the subject's mark; range: 0 (Not at all anxious) at the left-most point to 100 (Extremely anxious) at the right-most point. Performed prior to blood draws. | Baseline; 2 hours (h) before surgery (BS); 1, 2, and 3 h PS; Days 2, 3, 4, 5, 6, 7, 8, and 9 PS | 
| Baseline and Change From Baseline in EuroQol (EQ-5D) Health State Profile Score | EQ-5D is a self-administered questionnaire to assess health-related quality of life in 5 domains (mobility, self care, usual activities, pain or discomfort, and anxiety or depression). Scores from the 5 domains are used to calculate a single index value: the Health State Profile Score; range: 0.0 (death) to 1.0 (perfect health), higher scores indicating better health state. | Baseline and End of Treatment (EOT [Day 7 post surgery or Early Termination]) | 
| Change From Baseline in Pain Catastrophizing Scale (PCS) Total Score and Subscales | The PCS is a self-administered questionnaire with 13 items, each scored from 0 (not at all) to 4 (all the time) for extent to which participant catastrophizes postoperative pain. Total score is sum of scores for all questions (range: 0 to 52); Subscale scores: Rumination (sum of scores for 4 items; range: 0 to 16); Magnification (sum of scores for 3 items; range: 0 to 12); and Helplessness (sum of scores for 6 items; range: 0 to 24); higher scores mean a greater extent of pain catastrophizing. | 3 hours (h) post surgery (PS) and End of Treatment (EOT [Day 7 PS or Early Termination]) | 
| Relationship Between Baseline and Postoperative Pain Catastrophizing Scale (PCS) Score and Severity of Acute Pain and to Response to Therapy | The PCS is a self-administered questionnaire with 13 items, each scored from 0 (not at all) to 4 (all the time) for extent to which participant catastrophizes postoperative pain. Total score is sum of scores for all items (range: 0 to 52); higher scores mean a greater extent of pain catastrophizing. | Baseline and Days 1 and 7 post surgery (PS) | 
| Baseline and Change From Baseline in Short Form Acute Health Survey 12-Item Version (SF-12v2) Physical Component Summary Score (PCSS) and Mental Component Summary Score (MCSS) | PCSS and MCSS are component summary scores from the self-administered SF-12v2 acute health quality of life, norm-based survey. PCSS range: 4.95 to 76.13; MCSS range: -0.79 to 79.69; lowest scores mean very much below and highest scores mean very much above the general population average. | Baseline and End of Treatment (EOT [Day 7 post surgery or Early Termination]) | 
| Participants With Chronic Postoperative Pain | Number of participants who reported surgery-related pain at assessment (by answering 'yes' to a single question: In the last 24 hours, have you had pain in the area affected by your surgery?) | 1, 3, and 6 months (mo) post surgery (PS) | 
| Chronic Postoperative Pain: Pain Severity Index Score and Pain Interference Index Score on the Modified Brief Pain Inventory-Short Form (mBPI-sf) | m-BPI-sf: a self-administered 11-point Likert rating scale to rate pain in the past 24 hours. Pain interference index score is mean of 7 individual item scores for interference of pain with functional activities (general activity, mood, walking ability, relations with other people, sleep, normal work, and enjoyment of life); range: 0 (does not interfere) to 10 (completely interferes with functional activities). Pain severity index score is mean of 4 individual item scores for pain severity (pain right now, and worst, least, and average pain); range: 0 (no pain) to 10 (worst imaginable pain). | 1, 3, and 6 months (mo) post surgery (PS) | 
| Chronic Postoperative Pain: Total Score and Subscale Scores Using the Neuropathic Pain Symptom Inventory (NPSI) | NPSI: a 12-item self-administered questionnaire to assess the characteristics of neuropathic pain on average in the last 24 hours. 5 subscale scores include: burning spontaneous (spont.) pain, pressing spont. pain, paroxysmal pain, evoked pain, and paresthesia or dysesthesia (paresth/dysesth) (range: 0 [no pain] to 10 [worst pain imaginable]); total score calculated from the 5 pain subscores (range: 0 to 0.5), higher scores meaning worse pain. | 1, 3, and 6 months (mo) post surgery (PS) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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postoperative pain chronic pain