Opioid Analgesic Reduction Study

Study Overview
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Brief Summary
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The goal is to provide health care professionals, including dentists, with the best possible evidence for clinical decision making when deciding upon analgesics for acute post-surgical pain management, a double-blind, stratified randomized clinical trial will be conducted to test the hypothesis that a combination of over-the-counter non-opioid containing analgesics is at least as, if not more, effective (non-inferior) than the most commonly prescribed opioid analgesic. The impacted 3rd molar extraction model will be used due to the predictable severity of the post-operative pain and generalizability of results. This double-blind, prospective, stratified, randomized pragmatic clinical trial will use the impacted 3rd molar extraction pain model.

Official Title
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Opioid Analgesic Reduction Study (OARS): Managing Acute Post-Operative Surgical Pain

Conditions
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Opioid Use

Intervention / Treatment
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* Drug: opioid-containing analgesic
* Drug: two over-the-counter analgesics


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: An individual must meet all of the following criteria to be eligible to participate in the study: Be able to understand the informed consent. Provide signed and dated informed consent form Be able to understand all directions for data gathering instruments in English Be willing and able to comply with all study procedures and be available for the duration of the study Planning to undergo extraction of one or more partial or fully impacted mandibular 3rd molars Be 18 years or older Be in good general health as evidenced by medical history Women must agree to use one of the following methods of contraception while participating in this study: contraceptive pill intra-uterine device condoms abstinence Exclusion Criteria: Participants who self-report the following history will be excluded from participating: History of gastrointestinal bleeding and/or peptic ulcer History of renal disease (excluding kidney stones) History of hepatic disease History of bleeding disorder History of respiratory depression Any prior respiratory effect of an opioid or other anesthetic drugs that required respiratory support postoperatively Active or untreated asthma History of known allegoric reaction to ibuprofen, acetaminophen, hydrocodone, and/or anesthesia Currently taking any of the following medications: CYP3A4 inhibitor, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritonavir), which may increase plasma concentrations of hydrocodone bitartrate and acetaminophen and prolong opioid adverse reactions, and which may cause potentially fatal respiratory depression CNS depressants. Consumes 3 or more alcoholic drinks every day and/or has a history of alcoholism History of drug or alcohol abuse Family history of drug or alcohol abuse in a first-degree relative Has had no more than one opioid prescription filled within the past 12 months Currently pregnant or lactating Participants would also be excluded due to any additional criteria that would place the individual at increased risk or preclude the individual's full compliance with or completion of the study which includes: Prior participation in this study Inability or refusal to provide informed consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Opioid<br>Combination analgesic of hydrocodone 5mg/acetaminophen 300 mg and a placebo pill. | Drug: opioid-containing analgesic<br>* hydrocodone/ acetaminophen combination product<br>|
| Active Comparator: Non-Opioid<br>Combination of ibuprofen 400 mg/acetaminophen 500 mg | Drug: two over-the-counter analgesics<br>* combination of over-the-counter analgesics (ibuprofen/acetaminophen)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brief Pain Inventory pain scale using Numeric Rating Scale | Mean score (scale of 0 to 10, 0=no pain, 10=worst imaginable pain) | the first 24 hours post surgery | 
| Brief Pain Inventory pain scale using Numeric Rating Scale | Mean score (scale of 0 to 10, 0=no pain, 10=worst imaginable pain) | the first 48 hours post surgery | 
| Brief Pain Inventory pain scale using Numeric Rating Scale | Mean score (scale of 0 to 10, 0=no pain, 10=worst imaginable pain) | the first 7 days post surgery | 
| PTSS satisfaction questions assessing overall satisfaction | How satisfied are you with the TIME that it takes your pain medication to work? (5 pt. scale: 1=very satisfied, 5=very dissatisfied) How satisfied are you with the LEVEL OF AMOUNT of pain relief provided by your pain medication? (5 pt. scale: 1=very satisfied, 5=very dissatisfied) How satisfied are you with the DURATION of pain relief provided by your pain medication? (5 pt. scale: 1=very satisfied, 5=very dissatisfied) Overall, how satisfied are you with your pain medication? (5 pt. scale: 1=very satisfied, 5=very dissatisfied) Overall, how does your level of pain relief meet you expectations of pain relief? (5 pt. scale: 1=greatly exceeds my expectations, 5=does not meet my expectations at all) Do you think that your pain medication could be more effective in relieving your pain? (5 pt. scale: 1=yes, definitely, 5=definitely not) | At post operative visit (9 days after surgery +/- 5 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events experienced | Total adverse events experienced (count of yes answers to excessive fatigue or drowsiness, inability to concentrate, nausea, diarrhea, dizziness, constipation, skin rashes, stomach aches, heartburn, vomiting, euphoria, headache, urinary retention and unintentional weight gain) | Total events recorded each morning and evening after surgery for the first 24 hours post surgery | 
| Adverse events experienced | Total adverse events experienced (count of yes answers to excessive fatigue or drowsiness, inability to concentrate, nausea, diarrhea, dizziness, constipation, skin rashes, stomach aches, heartburn, vomiting, euphoria, headache, urinary retention and unintentional weight gain) | Total events recorded each morning and evening after surgery for the first 48 hours post surgery | 
| Adverse events experienced | Total adverse events experienced (count of yes answers to excessive fatigue or drowsiness, inability to concentrate, nausea, diarrhea, dizziness, constipation, skin rashes, stomach aches, heartburn, vomiting, euphoria, headache, urinary retention and unintentional weight gain) | Total events recorded each morning and evening for the first 7 days post surgery | 
| Pain interference (daily function) | Mean score of Patient-Reported Outcomes Measurement Information System questions related to pain interference: During the post-operative period, how much did pain interfere with your day to day activities, work around the home, ability to participate in social activities, enjoyment of life, the things you usually do for fun, enjoyment of social activities, household chores, family life, your ability to concentrate, enjoyment of recreational activities, tasks away from home {scale: 1=not at all, 2=a little bit, 3=somewhat, 4=quite a bit, 5=very much} and How often did pain keep you from socializing with others? {scale=1=never, 2=rarely, 3=sometimes, 4=often, 5=always} | Day 2 post surgery (recorded the evening of day 2) | 
| Pain interference (daily function) | Mean score of Patient-Reported Outcomes Measurement Information System questions related to pain interference: During the post-operative period, how much did pain interfere with your day to day activities, work around the home, ability to participate in social activities, enjoyment of life, the things you usually do for fun, enjoyment of social activities, household chores, family life, your ability to concentrate, enjoyment of recreational activities, tasks away from home {scale: 1=not at all, 2=a little bit, 3=somewhat, 4=quite a bit, 5=very much} and How often did pain keep you from socializing with others? {scale=1=never, 2=rarely, 3=sometimes, 4=often, 5=always} | Days 2 and 3 post surgery (recorded the evenings of days 2 and 3) | 
| Pain interference (daily function) | Mean score of Patient-Reported Outcomes Measurement Information System questions related to pain interference: During the post-operative period, how much did pain interfere with your day to day activities, work around the home, ability to participate in social activities, enjoyment of life, the things you usually do for fun, enjoyment of social activities, household chores, family life, your ability to concentrate, enjoyment of recreational activities, tasks away from home {scale: 1=not at all, 2=a little bit, 3=somewhat, 4=quite a bit, 5=very much} and How often did pain keep you from socializing with others? {scale=1=never, 2=rarely, 3=sometimes, 4=often, 5=always} | First 7 days post surgery | 
| Sleep quality (Questions from PSQ-3) | • Pain and Sleep Questionnaire three-item index : a. Last night did you have trouble falling asleep? b. Last night were you awakened by pain during the night? c. Were you awakened by pain this morning? {Binary yes/no) | For the first night post surgery | 
| Sleep quality (Questions from PSQ-3) | • Pain and Sleep Questionnaire three-item index : a. Last night did you have trouble falling asleep? b. Last night were you awakened by pain during the night? c. Were you awakened by pain this morning? {Binary yes/no) | For the first 2 nights post surgery | 
| Sleep Quality (Questions from PSQ-3) | • Pain and Sleep Questionnaire three-item index : a. Last night did you have trouble falling asleep? b. Last night were you awakened by pain during the night? c. Were you awakened by pain this morning? {Binary yes/no) | For the first 7 nights post surgery | 
| Sleep Quality (PSQ-3) | • Pain and Sleep Questionnaire three-item index : a. Last night did you have trouble falling asleep? b. Last night were you awakened by pain during the night? c. Were you awakened by pain this morning? NRS scale where 0=never, 10=always | Recorded during Visit 2 (Post operative visit 9 days +/-5 days post surgery) | 
| Overall satisfaction with sleep | NRS where 0=never, 10=always | For the first 7 evenings post surgery | 
| Overall satisfaction with sleep | From PTSS: Rating the overall quality of last night's sleep {NRS where 0=excellent and10=very poor} | For the first 7 evenings post surgery | 
| Potential for opioid tablet diversion | Number of returned analgesic capsules at post operative visit (9 days after surgery +/- 5 days) | At post operative visit (9 days after surgery +/- 5 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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3rd molar extraction pain model, Opioid Analgesics, Opioid Diversion, Over the counter analgesics, Acetaminophen, Ibuprofen, Hydrocodone, Opioid Addiction, Pain Management, Satisfaction