Study Of The Efficacy And Safety Of Pregabalin Compared To Placebo For Treatment Of Post-Surgical Pain From Hysterectomy

Pfizer's Upjohn has merged with Mylan to form Viatris Inc.501 enrolled

Overview

To assess the efficacy of pregabalin compared to placebo on pain following hysterectomy , measured using subject reported assessments of pain.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

501

Conditions

Pain, Postoperative

Interventions

pregabalin (Lyrica)DRUG

150 mg/day double blind (divided doses)

pregabalin (Lyrica)DRUG

300 mg/day double blind (divided doses)

matched placeboDRUG

matched placebo

Eligibility

Sex: FEMALEMin age: 25 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion Criteria: * The subject will have elective total abdominal hysterectomy using a transverse incision with or without bilateral salpingo-oophorectomy. The total hysterectomy may, however, be cervix-sparing. * The subject is expected to remain at the hospital (or intermediate care facility) for a minimum of 2 days following surgery. * The subject's preoperative health is graded as the American Society of Anesthesiologist P1 to P2. Exclusion Criteria: * Subjects having vaginal hysterectomy (whether laparoscopically assisted or not) * Subjects having additional procedures (such as those involving the bladder) at the same time as the total abdominal hysterectomy * The use of nerve block, spinal anesthesia or epidural anesthesia for post-surgical pain control * Subjects who have been using any opioid medications 2 weeks or more continuously within 3 months prior to the screening visit. * The subject has taken any NSAID or any analgesic other than acetaminophen within 3 days prior to surgery or is unwilling to abstain from NSAIDs or other analgesics, except as specified in the protocol, during the study. (Subjects taking \<325 mg per day of aspirin at a stable dose for at least 30 days before the first dose of study medication will be allowed to continue their aspirin regimen for the duration of the study).

Locations (42)

Outcomes

Primary Outcomes

Worst Pain Using the Modified Brief Pain Inventory - Short Form (m-BPI-sf)

Modified Brief Pain Inventory - Short Form (m-BPI-sf): participant rated 11-point Likert rating scale ranged from 0 (no pain) to 10 (worst pain imaginable). Least Square (LS) Means adjusted for treatment, pooled center and salpingo-oophorectomy strata.

Time frame: Day 2 (24 hours post surgery [PS])

Secondary Outcomes

Current Pain - Pain With Movement Caused by Sitting

Participant sat upright from supine position, followed by 120 second (sec) rest period, during which participant asked to rate pain with movement. Assessment performed 3 times each day of hospital stay, with 1 daily assessment at 24 (+/- 2) hour interval from end of surgery. Current pain reported on 11 point Likert scale 0 (no pain) to 10 (worst pain imaginable). LS Means adjusted for treatment, pooled center and salpingo-oophorectomy strata.

Time frame: Day 1 (day of surgery), up to 7 days PS, Discharge, 2 and 4 weeks PS

Current Pain - Pain With Movement Caused by Peak Expiratory (PEF) Test

Current pain with movement caused by peak expiratory flow (PEF) test as reported by participant on 11 point Likert scale 0 (no pain) to 10 (worst pain). Assessment performed 3 times each day of hospital stay, with 1 daily assessment at 24 (+/- 2) hour interval from end of surgery. PEF test performed 3 times, with 120sec rest periods in between. At beginning of each rest period, participant asked to rate pain caused by forced expiration. LS Means adjusted for treatment, pooled center and salpingo-oophorectomy strata.

Time frame: Day 1, up to 7 days PS, 2 and 4 weeks PS

Area Under the Curve (AUC) Pain - Pain With Movement Caused by Sitting

Time-normalized AUC of pain with movement caused by sitting reported by participants. Participant sat upright from supine position, followed by a 120sec rest period, during which the participant asked to rate pain with movement. Assessment performed 3 times each day of hospital stay, with 1 daily assessment at 24 (+/- 2) hour interval from end of surgery. Current pain reported on 11 point Likert scale 0 (no pain) to 10 (worst pain imaginable). LS Means adjusted for treatment, pooled center and salpingo-oophorectomy strata.

Data from ClinicalTrials.gov

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Pfizer Investigational Site

Mobile, Alabama, United States

Pfizer Investigational Site

Glendale, Arizona, United States

Pfizer Investigational Site

Phoenix, Arizona, United States

Pfizer Investigational Site

Phoenix, Arizona, United States

Pfizer Investigational Site

Phoenix, Arizona, United States

Pfizer Investigational Site

Glendale, California, United States

Pfizer Investigational Site

Pasadena, California, United States

Pfizer Investigational Site

Miami, Florida, United States

Pfizer Investigational Site

Miami, Florida, United States

Pfizer Investigational Site

Philadelphia, Pennsylvania, United States

...and 32 more locations

Time frame: 48 +/- 4 hours PS

Area Under the Curve (AUC) Pain - Pain With Movement Caused by Peak Expiratory Flow (PEF) Test

Time-normalized AUC of pain reported by participants with movement caused by PEF test. Pain reported by participant on 11 point Likert scale 0 (no pain) to 10 (worst pain). PEF test performed 3 times, with 120sec rest periods in between. At beginning of each rest period, participant asked to rate pain caused by forced expiration. LS Means adjusted for treatment, pooled center and salpingo-oophorectomy strata.

Time frame: 48 +/- 4 hours PS

Current Pain at Rest

Pain reported by participants at rest (numeric rating scale (NRS) - Current Pain) on an 11 point Likert scale 0 (no pain) - 10 (worst pain). Pain at rest during the hospital stay was assessed just before each Pain with Movement assessment. Assessment performed 3 times each day of hospital stay, with 1 of daily assessments at 24 (+/- 2 ) hour intervals from end of surgery. LS Means adjusted for treatment, pooled center and salpingo-oophorectomy strata.

Time frame: 8, 16, 24, 32, 40, 48 hours PS

Area Under the Curve (AUC) of Pain at Rest During the First Two Days of Hospital Stay

Time-normalized AUC of pain reported by participants on 11 point Likert scale 0 (no pain) to 10 (worst pain). LS Means adjusted for treatment, pooled center and salpingo-oophorectomy strata.

Time frame: 48 +/- 4 hours PS

Total Cumulative Dose of Opioids Following Surgery

Total cumulative dose was calculated as milligram (mg) of morphine equivalent and included opioids administered by any route. LS Means adjusted for treatment, pooled center and salpingo-oophorectomy strata.

Time frame: 24, 48 Hours PS, Discharge (day 3 up to day 7 PS)

Integrated Analgesic Score

The integrated analgesic score (a combination of opioid use and either worst pain, or pain at rest, or pain caused by sitting, or pain caused by forced expiration as defined by Silverman et al 1993) was the sum of percent differences from mean rank for pain and opioids and ranged from -200 to 200 where lower values represent improvement. LS Means adjusted for treatment, pooled center and salpingo-oophorectomy strata.

Time frame: 0-24, 24-48, 48-72 hours PS

Non-opioid Rescue Medication - Paracetamol

The amounts of non-opioid rescue medications, paracetamol, used by the participants during the study, including anti-emetic medications.

Time frame: 24, 48, 72 hours PS, Discharge (day 3 up to day 7 PS), Week 1, 2, 3, 4 PS,

Anxiety Before and After Surgery

Participant anxiety reported on Visual Anxiety Scale (VAS), 0 (not at all anxious) to 100 (extremely anxious). LS Means adjusted for treatment, pooled center and salpingo-oophorectomy strata

Time frame: Surgery day before first dose and 1 hour after first dose, Day 1, 2, 3, 4, 5 PS and Discharge (day 3 up to day 7 PS)

Non-opioid Rescue Medication - Ibuprofen

The amounts of non-opioid rescue medications, ibuprofen, used by the participants during the study, including anti-emetic medications.

Time frame: 24, 48, 72 hours PS, Discharge (day 3 up to day 7 PS), Week 1, 2, 3, 4 PS

Percent Change From Baseline in Peak Expiratory Flow

Change from baseline= PEF at x hours minus PEF at baseline; possible values ranged from 0-900 liters/minute (higher values indicated better lung function). LS Means adjusted for treatment, pooled center and salpingo-oophorectomy strata.

Time frame: Baseline, every 8 hours (up to 232 hours) PS, and Discharge (Day 3-7 PS flexible)

Timed Up-and-Go (TUG)

Functional mobility test performed once a day at 24 hour intervals from surgery after the pain with movement assessment. LS Means adjusted for treatment, pooled center and salpingo-oophorectomy strata.

Time frame: Day 1, 2, 3, 4, 5 PS and Discharge (day 3 up to day 7 PS)

Average Daily Pain

Post-discharge average pain as measured in daily participant diaries NRS an 11 point Likert scale ranged from 0 (no pain) to 10 (worst pain). LS Means adjusted for treatment, pooled center and salpingo-oophorectomy strata.

Time frame: Day 2, 3, 4, 5, 6, 7, PS; week 2, 3, 4 PS

Worst Daily Pain

Post-discharge worst pain as measured in daily participant diaries NRS an 11 point Likert scale that ranged from 0 (no pain) to 10 (pain as bad as you can imagine). LS Means from ANOVA model with terms of treatment, pooled center, salpingo-oophorectomy strata and baseline worst pain score.

Time frame: Discharge (day 3 up to day 7 PS), Day 7, 14, 28 PS

Sleep Interference

Sleep interference post surgery measured daily in participant diaries; NRS of how pain interfered with sleep during the last 24 hours, ranged from 0 (does not interfere) to 10 (completely interferes). LS Means adjusted for treatment, pooled center and salpingo-oophorectomy strata.

Time frame: Daily post hospital discharge ( Day 2-7 PS), Week 2, 3, 4 PS

Brief Pain Inventory-Short Form (m-BPI-sf): Pain Interference Index Scores

m-BPI-sf: participant-rated 11 point Likert rating scale ranging from 0 (does not interfere) to 10 (completely interferes) with functional activities (general activity, mood, walking ability, relations with other people, sleep, normal work, and enjoyment of life) in past 24 hours. LS Means adjusted for treatment, pooled center and salpingo-oophorectomy strata.

Time frame: Baseline, Discharge (day 3 up to day 7 PS), Day 7, 14, 28 PS

Brief Pain Inventory-Short Form (m-BPI-sf): Pain Severity Index Scores

m-BPI-sf: participant rated 11-point Likert rating scale ranging from 0 (no pain) to 10 (worst pain possible). Pain severity index is the mean of item scores 2, 3, and 4 (pain right now, worst pain, and average pain level). LS Means adjusted for treatment, pooled center and salpingo-oophorectomy strata.

Time frame: Baseline, Discharge (day 3 up to day 7 PS), Day 7, 14, 28 PS

Participant Satisfaction With Study Medication - Surgery Day

Participant satisfaction with study medication using the Global Evaluation of Study Medication questionaire. Participants overall impression (global evaluation) of the study medication was recorded by the participant by answering the following question: How would you rate the study medication you received for pain? Excellent 4; Good 3; Fair 2; Poor 1.

Time frame: Day 1

Participant Satisfaction With Study Medication - Day 1 PS

Time frame: Day 1 PS

Participant Satisfaction With Study Medication - Day 2 PS

Time frame: Day 2 PS

Participant Satisfaction With Study Medication - Day 3 PS

Time frame: Day 3 PS

Participant Satisfaction With Study Medication - Day 4 PS

Time frame: Day 4 PS

Participant Satisfaction With Study Medication - Day 5 PS

Time frame: Day 5 PS

Participant Satisfaction With Study Medication - Discharge

Time frame: Discharge (day 3 up to day 7 PS)

Participant Satisfaction With Study Medication - Day 7 PS

Time frame: Day 7 PS

Participant Satisfaction With Study Medication - Day 14 PS

Time frame: Day 14 PS

Participant Satisfaction With Study Medication - Day 28 PS

Time frame: Day 28 PS

Pain Treatment Satisfaction Scale (PTSS): Satisfaction With Current Pain Medication

Satisfaction with current pain medication ranged from 0 (worst possible response) to100 (best possible response). LS Means adjusted for treatment, pooled center and salpingo-oophorectomy strata.

Time frame: Discharge (day 3 up to day 7 PS), Day 28 PS

Pain Treatment Satisfaction Scale (PTSS): Impact of Current Pain Medication

Impact of current pain medication response scale: 0 (worst possible response) to 100 (best possible response). LS Means adjusted for treatment, pooled center and salpingo-oophorectomy strata.

Time frame: Discharge (day 3 up to day 7 PS), Day 28 PS

Quality of Life Using EuroQol (EQ-5D) Health State Profile

Participant rated questionnaire assessed current health for 6 domains: mobility/self-care/ usual activities/pain/discomfort/anxiety and depression. Scoring developed by EuroQol Group assigned a utility value for each domain in the profile. Scores ranged from 1 better health (no problems) to 3 worst health (eg, "confined to bed"). Score transformed and resulted in a total score range -0.594 to 1.000; higher score=better health state. Health profile scores estimated using Dolan computational algorithms 1997 and 2001. LS Means adjusted for treatment/pooled center/salpingo-oophorectomy strata.

Time frame: Discharge (day 3 up to day 7 PS) and day 28 PS

Time to Meet Hospital Discharge Criteria

Mean time from end of surgery to meet protocol defined hospital discharge criteria: participant no longer received parental opioids, was able to dress and mobilize without assistance, and had normal intake of food and fluids.

Time frame: Day 1 up to Day 7 PS

Time to Actual Discharge

Mean time from end of surgery to actual hospital discharge. Participant was expected to remain at the hospital for a minimum of 2 days following surgery.

Time frame: Day 1 up to Day 7 PS

Incidence of Chronic Post-operative Pain

Chronic post-operative pain as a result of abdominal hysterectomy as reported by participants on PS questionaire of pain within last 24 hours in area affected by surgery.

Time frame: 3 and 6 Months PS

Total Clinically Meaningful Event (CME) Score

Total CME score calculated by summing the number of Clinically Meaningful Events (CMEs) across symptoms. CME for each symptom will be defined using the Opioid-Related Symptom Distress Scale (OR-SDS) a participant rated scale of symptoms within the last 24 hours. Total CME score could range from 0 to 9. LS Means adjusted for treatment, pooled center and salpingo-oophorectomy strata.

Time frame: Surgery Day, Day 1, 2, 3, 4, 5 PS, Discharge (day 3 up to day 7 PS), Day 7, 14, 28 PS