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

This study has been completed.
Sponsor:
Information provided by:
Pfizer
ClinicalTrials.gov Identifier:
NCT00468845
First received: May 1, 2007
Last updated: June 7, 2011
Last verified: June 2011
  Purpose

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


Condition Intervention Phase
Pain, Postoperative
Drug: pregabalin (Lyrica)
Drug: matched placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Worst Pain Using the Modified Brief Pain Inventory - Short Form (m-BPI-sf) [ Time Frame: Day 2 (24 hours post surgery [PS]) ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • Current Pain - Pain With Movement Caused by Sitting [ Time Frame: Day 1 (day of surgery), up to 7 days PS, Discharge, 2 and 4 weeks PS ] [ Designated as safety issue: No ]
    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.

  • Current Pain - Pain With Movement Caused by Peak Expiratory (PEF) Test [ Time Frame: Day 1, up to 7 days PS, 2 and 4 weeks PS ] [ Designated as safety issue: No ]
    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.

  • Area Under the Curve (AUC) Pain - Pain With Movement Caused by Sitting [ Time Frame: 48 +/- 4 hours PS ] [ Designated as safety issue: No ]
    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.

  • Area Under the Curve (AUC) Pain - Pain With Movement Caused by Peak Expiratory Flow (PEF) Test [ Time Frame: 48 +/- 4 hours PS ] [ Designated as safety issue: No ]
    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.

  • Current Pain at Rest [ Time Frame: 8, 16, 24, 32, 40, 48 hours PS ] [ Designated as safety issue: No ]
    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.

  • Area Under the Curve (AUC) of Pain at Rest During the First Two Days of Hospital Stay [ Time Frame: 48 +/- 4 hours PS ] [ Designated as safety issue: No ]
    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.

  • Total Cumulative Dose of Opioids Following Surgery [ Time Frame: 24, 48 Hours PS, Discharge (day 3 up to day 7 PS) ] [ Designated as safety issue: No ]
    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.

  • Integrated Analgesic Score [ Time Frame: 0-24, 24-48, 48-72 hours PS ] [ Designated as safety issue: No ]
    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.

  • Non-opioid Rescue Medication - Paracetamol [ Time Frame: 24, 48, 72 hours PS, Discharge (day 3 up to day 7 PS), Week 1, 2, 3, 4 PS, ] [ Designated as safety issue: No ]
    The amounts of non-opioid rescue medications, paracetamol, used by the participants during the study, including anti-emetic medications.

  • Anxiety Before and After Surgery [ 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) ] [ Designated as safety issue: No ]
    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

  • Non-opioid Rescue Medication - Ibuprofen [ Time Frame: 24, 48, 72 hours PS, Discharge (day 3 up to day 7 PS), Week 1, 2, 3, 4 PS ] [ Designated as safety issue: No ]
    The amounts of non-opioid rescue medications, ibuprofen, used by the participants during the study, including anti-emetic medications.

  • Percent Change From Baseline in Peak Expiratory Flow [ Time Frame: Baseline, every 8 hours (up to 232 hours) PS, and Discharge (Day 3-7 PS flexible) ] [ Designated as safety issue: No ]
    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.

  • Timed Up-and-Go (TUG) [ Time Frame: Day 1, 2, 3, 4, 5 PS and Discharge (day 3 up to day 7 PS) ] [ Designated as safety issue: No ]
    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.

  • Average Daily Pain [ Time Frame: Day 2, 3, 4, 5, 6, 7, PS; week 2, 3, 4 PS ] [ Designated as safety issue: No ]
    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.

  • Worst Daily Pain [ Time Frame: Discharge (day 3 up to day 7 PS), Day 7, 14, 28 PS ] [ Designated as safety issue: No ]
    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.

  • Sleep Interference [ Time Frame: Daily post hospital discharge ( Day 2-7 PS), Week 2, 3, 4 PS ] [ Designated as safety issue: No ]
    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.

  • Brief Pain Inventory-Short Form (m-BPI-sf): Pain Interference Index Scores [ Time Frame: Baseline, Discharge (day 3 up to day 7 PS), Day 7, 14, 28 PS ] [ Designated as safety issue: No ]
    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.

  • Brief Pain Inventory-Short Form (m-BPI-sf): Pain Severity Index Scores [ Time Frame: Baseline, Discharge (day 3 up to day 7 PS), Day 7, 14, 28 PS ] [ Designated as safety issue: No ]

    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.


  • Participant Satisfaction With Study Medication - Surgery Day [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    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.

  • Participant Satisfaction With Study Medication - Day 1 PS [ Time Frame: Day 1 PS ] [ Designated as safety issue: No ]
    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.

  • Participant Satisfaction With Study Medication - Day 2 PS [ Time Frame: Day 2 PS ] [ Designated as safety issue: No ]
    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.

  • Participant Satisfaction With Study Medication - Day 3 PS [ Time Frame: Day 3 PS ] [ Designated as safety issue: No ]
    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.

  • Participant Satisfaction With Study Medication - Day 4 PS [ Time Frame: Day 4 PS ] [ Designated as safety issue: No ]
    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.

  • Participant Satisfaction With Study Medication - Day 5 PS [ Time Frame: Day 5 PS ] [ Designated as safety issue: No ]
    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.

  • Participant Satisfaction With Study Medication - Discharge [ Time Frame: Discharge (day 3 up to day 7 PS) ] [ Designated as safety issue: No ]
    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.

  • Participant Satisfaction With Study Medication - Day 7 PS [ Time Frame: Day 7 PS ] [ Designated as safety issue: No ]
    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.

  • Participant Satisfaction With Study Medication - Day 14 PS [ Time Frame: Day 14 PS ] [ Designated as safety issue: No ]
    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.

  • Participant Satisfaction With Study Medication - Day 28 PS [ Time Frame: Day 28 PS ] [ Designated as safety issue: No ]
    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.

  • Pain Treatment Satisfaction Scale (PTSS): Satisfaction With Current Pain Medication [ Time Frame: Discharge (day 3 up to day 7 PS), Day 28 PS ] [ Designated as safety issue: No ]
    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.

  • Pain Treatment Satisfaction Scale (PTSS): Impact of Current Pain Medication [ Time Frame: Discharge (day 3 up to day 7 PS), Day 28 PS ] [ Designated as safety issue: No ]
    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.

  • Quality of Life Using EuroQol (EQ-5D) Health State Profile [ Time Frame: Discharge (day 3 up to day 7 PS) and day 28 PS ] [ Designated as safety issue: No ]
    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 to Meet Hospital Discharge Criteria [ Time Frame: Day 1 up to Day 7 PS ] [ Designated as safety issue: No ]
    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 to Actual Discharge [ Time Frame: Day 1 up to Day 7 PS ] [ Designated as safety issue: No ]
    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.

  • Incidence of Chronic Post-operative Pain [ Time Frame: 3 and 6 Months PS ] [ Designated as safety issue: No ]
    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.

  • Total Clinically Meaningful Event (CME) Score [ Time Frame: Surgery Day, Day 1, 2, 3, 4, 5 PS, Discharge (day 3 up to day 7 PS), Day 7, 14, 28 PS ] [ Designated as safety issue: No ]
    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.


Enrollment: 501
Study Start Date: June 2007
Study Completion Date: October 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: pregabalin (Lyrica)
150 mg/day double blind (divided doses)
Experimental: 2 Drug: pregabalin (Lyrica)
300 mg/day double blind (divided doses)
Placebo Comparator: 3 Drug: matched placebo
matched placebo

  Eligibility

Ages Eligible for Study:   25 Years to 70 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00468845

  Show 42 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Director, Clinical Trials Disclosure Group, Pfizer, Inc
ClinicalTrials.gov Identifier: NCT00468845     History of Changes
Other Study ID Numbers: A0081153
Study First Received: May 1, 2007
Results First Received: April 29, 2011
Last Updated: June 7, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
pain after hysterectomy
amount of opioids used

Additional relevant MeSH terms:
Pain, Postoperative
Postoperative Complications
Pathologic Processes
Pain
Signs and Symptoms
Pregabalin
Gamma-Aminobutyric Acid
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Anticonvulsants
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
GABA Agents
Neurotransmitter Agents

ClinicalTrials.gov processed this record on September 18, 2014