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

Pain, Postoperative Clinical Trial

Official title:

A Multiple Dose, Randomized, Double-Blind Multicenter Study Of The Efficacy And Safety Of Pregabalin Compared To Placebo In The Treatment Of Patients With Post-Surgical Pain From Hysterectomy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00468845
• Other study ID #: A0081153
• Status: Completed
• Phase: Phase 3
• Start date: June 2007
• Est. completion date: October 2010

Study information

• Verified date: June 2011
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 501
• Est. completion date: October 2010
• Est. primary completion date: May 2010
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 25 Years to 70 Years

Eligibility

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).

Related Conditions & MeSH terms

• Pain, Postoperative

Intervention

Drug:
• pregabalin (Lyrica)
150 mg/day double blind (divided doses)
• pregabalin (Lyrica)
300 mg/day double blind (divided doses)
• matched placebo
matched placebo

Locations

Country	Name	City	State
Canada	Pfizer Investigational Site	Calgary	Alberta
Canada	Pfizer Investigational Site	Montreal	Quebec
Canada	Pfizer Investigational Site	Sherbrooke	Quebec
Czechia	Pfizer Investigational Site	Praha 5
Hong Kong	Pfizer Investigational Site	Kowloon
Hong Kong	Pfizer Investigational Site	Shatin
South Africa	Pfizer Investigational Site	Cape Town	Western Cape
South Africa	Pfizer Investigational Site	Johannesburg	Gauteng
South Africa	Pfizer Investigational Site	Krugersdorp	Gauteng
South Africa	Pfizer Investigational Site	Ladysmith	KZN
South Africa	Pfizer Investigational Site	Newcastle	KwaZulu Natal
South Africa	Pfizer Investigational Site	Parktown
South Africa	Pfizer Investigational Site	Pretoria	Gauteng
Spain	Pfizer Investigational Site	Cadiz
Spain	Pfizer Investigational Site	Madrid
Spain	Pfizer Investigational Site	Madrid
Spain	Pfizer Investigational Site	Valencia
Sweden	Pfizer Investigational Site	Lund
Sweden	Pfizer Investigational Site	Orebro
Sweden	Pfizer Investigational Site	Stockholm
Thailand	Pfizer Investigational Site	Bangkoknoi	Bangkok
Thailand	Pfizer Investigational Site	Muang	Chiang Mai
Thailand	Pfizer Investigational Site	Muang	Khon Kaen
United Kingdom	Pfizer Investigational Site	Birmingham
United Kingdom	Pfizer Investigational Site	Edinburgh	Scotland
United Kingdom	Pfizer Investigational Site	Leicester	Leicestershire
United Kingdom	Pfizer Investigational Site	Liverpool
United Kingdom	Pfizer Investigational Site	Livingstone
United States	Pfizer Investigational Site	Glendale	California
United States	Pfizer Investigational Site	Glendale	Arizona
United States	Pfizer Investigational Site	Houston	Texas
United States	Pfizer Investigational Site	Houston	Texas
United States	Pfizer Investigational Site	Miami	Florida
United States	Pfizer Investigational Site	Miami	Florida
United States	Pfizer Investigational Site	Mobile	Alabama
United States	Pfizer Investigational Site	Pasadena	California
United States	Pfizer Investigational Site	Philadelphia	Pennsylvania
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	Pittsburgh	Pennsylvania
United States	Pfizer Investigational Site	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

Countries where clinical trial is conducted

United States,  Canada,  Czechia,  Hong Kong,  South Africa,  Spain,  Sweden,  Thailand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Percentage of Participants With Wound Healing Complications - Discharge	Pre-specified adverse events of wound healing complications based on Center for Disease Control and Prevention, 1999, guidelines for prevention of surgical site infection (SSI) wound healing complications included: superficial incisional SSI, deep incisional SSI, organ/space SSI or non-infections wound healing complication.	Discharge (day 3 up to day 7 PS)
Other	Percentage of Participants With Wound Healing Complications - Day 7 PS	Pre-specified adverse events of wound healing complications based on Center for Disease Control and Prevention, 1999, guidelines for prevention of surgical site infection (SSI) wound healing complications included: superficial incisional SSI, deep incisional SSI, organ/space SSI or non-infections wound healing complication.	Day 7 PS
Other	Percentage of Participants With Wound Healing Complications - Day 14 PS	Pre-specified adverse events of wound healing complications based on Center for Disease Control and Prevention, 1999, guidelines for prevention of surgical site infection (SSI) wound healing complications included: superficial incisional SSI, deep incisional SSI, organ/space SSI or non-infections wound healing complication.	Day 14 PS
Other	Percentage of Participants With Wound Healing Complications - Day 28 PS	Pre-specified adverse events of wound healing complications based on Center for Disease Control and Prevention, 1999, guidelines for prevention of surgical site infection (SSI) wound healing complications included: superficial incisional SSI, deep incisional SSI, organ/space SSI or non-infections wound healing complication.	Day 28 PS
Other	Percentage of Participants With Wound Healing Complications - End of Treatment	Pre-specified adverse events of wound healing complications based on Center for Disease Control and Prevention, 1999, guidelines for prevention of surgical site infection (SSI) wound healing complications included: superficial incisional SSI, deep incisional SSI, organ/space SSI or non-infections wound healing complication.	Day 1 up to Day 28 PS
Other	Incision Length Correlated With Worst Pain	Incision length (cm) correlated with worst pain. Worst pain ranged from 0 (no pain) to 10 (worst pain imaginable). LS Means adjusted for treatment, pooled center, salpingo-oophorectomy strata.	Day 1
Other	Neuropathic Pain Symptom Inventory (NPSI)	Pain characteristics in participants who reported pain (mBPI-sf, NPSI); NPSI a participant rated questionnaire to evaluate different symptoms of neuropathic pain, burning spontaneous pain, pressing spontaneous pain, paroxysmal pain, evoked pain, and paresthesia/dysesthesia at discharge. NPSI Total Score ranged from 0 to 0.5; NPSI subscales pain ranged from 0 (no pain) to 10 (worst pain). LS Means adjusted for treatment, pooled center and salpingo-oophorectomy strata.	Discharge (day 3 up to day 7 PS)
Primary	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.	Day 2 (24 hours post surgery [PS])
Secondary	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.	Day 1 (day of surgery), up to 7 days PS, Discharge, 2 and 4 weeks PS
Secondary	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.	Day 1, up to 7 days PS, 2 and 4 weeks PS
Secondary	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.	48 +/- 4 hours PS
Secondary	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.	48 +/- 4 hours PS
Secondary	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.	8, 16, 24, 32, 40, 48 hours PS
Secondary	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.	48 +/- 4 hours PS
Secondary	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.	24, 48 Hours PS, Discharge (day 3 up to day 7 PS)
Secondary	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.	0-24, 24-48, 48-72 hours PS
Secondary	Non-opioid Rescue Medication - Paracetamol	The amounts of non-opioid rescue medications, paracetamol, used by the participants during the study, including anti-emetic medications.	24, 48, 72 hours PS, Discharge (day 3 up to day 7 PS), Week 1, 2, 3, 4 PS,
Secondary	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	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)
Secondary	Non-opioid Rescue Medication - Ibuprofen	The amounts of non-opioid rescue medications, ibuprofen, used by the participants during the study, including anti-emetic medications.	24, 48, 72 hours PS, Discharge (day 3 up to day 7 PS), Week 1, 2, 3, 4 PS
Secondary	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.	Baseline, every 8 hours (up to 232 hours) PS, and Discharge (Day 3-7 PS flexible)
Secondary	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.	Day 1, 2, 3, 4, 5 PS and Discharge (day 3 up to day 7 PS)
Secondary	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.	Day 2, 3, 4, 5, 6, 7, PS; week 2, 3, 4 PS
Secondary	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.	Discharge (day 3 up to day 7 PS), Day 7, 14, 28 PS
Secondary	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.	Daily post hospital discharge ( Day 2-7 PS), Week 2, 3, 4 PS
Secondary	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.	Baseline, Discharge (day 3 up to day 7 PS), Day 7, 14, 28 PS
Secondary	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.	Baseline, Discharge (day 3 up to day 7 PS), Day 7, 14, 28 PS
Secondary	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.	Day 1
Secondary	Participant Satisfaction With Study Medication - Day 1 PS	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.	Day 1 PS
Secondary	Participant Satisfaction With Study Medication - Day 2 PS	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.	Day 2 PS
Secondary	Participant Satisfaction With Study Medication - Day 3 PS	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.	Day 3 PS
Secondary	Participant Satisfaction With Study Medication - Day 4 PS	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.	Day 4 PS
Secondary	Participant Satisfaction With Study Medication - Day 5 PS	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.	Day 5 PS
Secondary	Participant Satisfaction With Study Medication - Discharge	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.	Discharge (day 3 up to day 7 PS)
Secondary	Participant Satisfaction With Study Medication - Day 7 PS	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.	Day 7 PS
Secondary	Participant Satisfaction With Study Medication - Day 14 PS	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.	Day 14 PS
Secondary	Participant Satisfaction With Study Medication - Day 28 PS	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.	Day 28 PS
Secondary	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.	Discharge (day 3 up to day 7 PS), Day 28 PS
Secondary	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.	Discharge (day 3 up to day 7 PS), Day 28 PS
Secondary	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.	Discharge (day 3 up to day 7 PS) and day 28 PS
Secondary	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.	Day 1 up to Day 7 PS
Secondary	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.	Day 1 up to Day 7 PS
Secondary	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.	3 and 6 Months PS
Secondary	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.	Surgery Day, Day 1, 2, 3, 4, 5 PS, Discharge (day 3 up to day 7 PS), Day 7, 14, 28 PS

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