Morphine-Sparing Efficacy Of Parecoxib In Pain Treatment After Radical Prostatectomy

Study Overview
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Brief Summary
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The primary objective of this study is to demonstrate the opioid-sparing efficacy of parecoxib 40 mg intravenously given as a loading dose followed by 20 mg intravenously in the 24 hours after the end of surgery.

Detailed Description
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The study was terminated due to lack of recruitment due to competing alternative operation methods on 13September 2010. The decision to terminate the trial was not based on any safety concerns.

Official Title
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Randomized, Double-Blind Study Of The Morphine-Sparing Efficacy And Safety Of Parecoxib Sodium 40 Mg IV Followed By 20 Mg IV Every 12 Hours In The Treatment Of Pain Following Radical Prostatectomy

Conditions
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Pain, Postoperative

Intervention / Treatment
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* Drug: Morphine, Parecoxib
* Drug: Morphine, Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient's ASA physical status is 1 or 2 and he has a low risk (i.e.,<10%) of developing an acute coronary event within the next 10 years according to the PROCAM risk assessment calculator. The patient is scheduled to undergo routine radical prostatectomy performed under a standardized regimen of general anesthesia, and is expected to experience moderate to severe postsurgical pain in the absence of postoperative analgesia. Exclusion Criteria: The patient has a history of uncontrolled chronic disease or a concurrent clinically significant illness or medical condition such as a diagnosed chronic pain condition, which, in the Investigator's opinion, would contraindicate study participation or confound interpretation of the results The patient has a history or current presence of congestive heart failure (NYHA II-IV), established ischaemic heart disease, peripheral arterial disease and / or cerebrovascular disease.

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| Active Comparator: Morphine plus Parecoxib<br> | Drug: Morphine, Parecoxib<br>* Parecoxib 40 milligrams (mg) administered intravenously immediately post surgery, followed 20 mg every 12 hours until 48 hours post surgery, total 5 doses. Participants also received Patient-Controlled Analgesia (PCA) 1 mg per dose, maximum 40 mg/4 hours, and if necessary, bolus (2 to 5 mg) before or after enabled PCA.<br>|
| Active Comparator: Morphine and Placebo<br> | Drug: Morphine, Placebo<br>* Matching placebo administered intravenously immediately post surgery and every 12 hours until 48 hours post surgery, total 5 doses. Participants also received PCA (1 mg per dose, maximum 40 mg/4 hours, and if necessary, bolus (2 to 5 mg) before or after enabled PCA<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative Amount of Morphine Administered in the First 24 Hours Following Surgery | Total cumulative amount of morphine administered (PCA and/or bolus) in the first 24 hours after the application of the last surgical stitch after prostatectomy. | 24 hours post surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative Amount of Morphine Administered in the First 48 Hours Following Surgery | Total cumulative amount of morphine administered (PCA and/or bolus) in the first 48 hours after the application of the last surgical stitch after prostatectomy. | 48 hours post surgery | 
| Time to Last Administration of Morphine | Time from last surgical stitch after prostatectomy to last administration of morphine (PCA and/or bolus). | baseline (end of surgery) to 48 hours post surgery | 
| Amount of Blood Loss | Calculated as: ([Hb g/dL]pra + RBCUduring48)-[Hb g/dL]at 48, where [Hb g/dL]pra=blood hemoglobin concentration preoperatively in grams per deciliter (g/dL), [Hb g/dL]at 48=blood hemoglobin concentration 48 hours after skin closure, and RBCUduring48=number of red blood cell units (RBCU) substituted during and after prostatectomy until 48 hours after skin closure. | 48 hours post surgery | 
| Number of Participants With Blood Loss Requiring Red Blood Cell (RBC) Transfused Units |  | 48 hours post surgery | 
| Pain Intensity Score | Pain intensity assessed immediately prior and 30 minutes after administration (admin) of study medication, participants categorized their pain intensity at rest and at movement on 0-4 numeric rating scale (NRS):0 (minimum intensity) to 4 (maximum intensity). Movement defined as sitting up from a lying into a sitting position in bed. | 12, 24, 36, and 48 hours post surgery | 
| Modified Brief Pain Inventory-Short Form (mBPI-sf): Pain Severity Composite Score | mBPI-sf: participant-rated 11-point Likert rating scale ranging from 0 (no pain) to 10 (pain as bad as you can imagine). Pain severity index=the mean of item scores 2 to 5 (pain at its worst in past 24 hours, pain at its least in past 24 hours, average pain level, and pain right now). | 24 and 48 hours post surgery | 
| Modified Brief Pain Inventory-Short Form (mBPI-sf): Pain Interference Composite Score | mBPI-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, coughing, deep breathing, and concentration) in past 24 hours. | 24 and 48 hours post surgery | 
| Opiate Related Symptom Distress Scale (OR-SDS) Questionnaire: Overall Composite Score | Participant-rated scale assessed 10 common opiate related symptoms by 3 ordinal measures: frequency (1 to 4 scale: rarely to almost constantly), severity (1 to 4 scale: slight to very severe) and bothersomeness (1 to 5 scale: not at all to very much). Frequency and severity items assigned numeric scores 1 to 4. Bothersomeness items scaled in order to assign numeric scores 0.8 to 4.0 (not at all scored=0.8, a little bit=1.6, somewhat=2.4, quite a bit=3.2, and very much=4.0). Overall composite score=mean of each 10 individual mean symptoms' OR-SDS scores; ranged from 1 to 4. | 24 and 48 hours post surgery |