Efficacy of Combined Ibuprofen and Acetaminophen Therapy Versus Ibuprofen Alone Versus Placebo Alone for Pain Management

Study Overview
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Brief Summary
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The purpose of this study is to compare the effectiveness of a combined ibuprofen and acetaminophen regimen in controlling discomfort for 4 days after initial orthodontic appliance placement as compared to ibuprofen alone or a placebo. The hypothesis is that combined ibuprofen and acetaminophen therapy will effectively provide better pain control than ibuprofen alone or a placebo after orthodontic appliance placement.

Detailed Description
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Orthodontic pain is often reported for the first 4 days after the appliances are attached. This study will investigate two modes of pain management versus a placebo. Consented subjects will be randomly assigned to one of 3 groups: Group A, a combined and simultaneous therapy of 200 mg ibuprofen and 650 mg acetaminophen (3 pills total) taken orally at set time intervals (0 h, 6 h, 12 h, and 24h, 48h, 72h, and 96h); Group B, ibuprofen alone (200 mg) taken orally at same time intervals (1 ibuprofen and 2 placebo pills); Group C, placebo taken orally at the same time intervals (3 placebo pills). The study will be blinded for the investigators, patients, and statisticians.

Official Title
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Efficacy of Combined Ibuprofen and Acetaminophen Therapy Versus Ibuprofen Alone Versus Placebo Alone for Pain of Initial Orthodontic Wire Insertion: a Randomized Controlled Trial

Conditions
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Pain, Orofacial

Intervention / Treatment
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* Drug: Ibuprofen 200 mg and acetaminphen 650 mg
* Drug: Ibuprofen 200 mg
* Drug: Placebo oral tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: scheduled to begin comprehensive orthodontic treatment (banding/bonding of at least 10 teeth in 1 arch and archwire placement in at least 1 arch); extractions, if required, performed at least 2 weeks before appliance and archwire placement; healthy with no significant medical findings; no prophylactic antibiotic coverage required; currently not taking antibiotics or analgesics; no contraindications to the use of acetaminophen or ibuprofen; and minimum age of 12 years Exclusion Criteria: Under the age of 12 or over the age of 80, prisoners, pregnant women, decisionally challenged individuals, allergy to either medication, history of kidney disease, liver damage or disease, alcoholism/use of 3 or more alcoholic drinks during study period, use of blood thinners, stomach ulcers or stomach bleeding.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 80 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Two investigational groups and a placebo group
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ibuprofen<br>one 200 mg tablet of ibuprofen and 2 placebo tablets | Drug: Ibuprofen 200 mg<br>* For morning appliance placement: dose #1 at approximately 9:00 a.m. as appointment starts; dose #2 6 hours later (3:00 p.m- or as soon after school and close to 3 pm as possible.); dose #3 another 6 hours later (9:00 p.m.); dose #4 the following morning upon waking (approximately 24 hours from start and patient will record the time), doses #5 through #7 will be taken every morning upon waking on the second, third, and fourth days, respectively. For afternoon appliance placement: dose #1 at approximately 2:00 p.m. as appointment starts; dose #2 6 hours later (8:00 p.m.); dose #3 the following morning upon waking (approximately 12 hours later and patient will record the time); dose #4 6 hours later from dose #3 (approximately 24 hours from the initial dose) around 2:00 p.m. (or as soon after school as possible) doses #5 through #7 will be taken every afternoon at 2:00 p.m. on the second, third, and fourth days, respectively.<br>|
| Experimental: Ibuprofen and acetaminophen<br>one 200 mg table of ibuprofen and two 325 mg tablets of acetaminophen | Drug: Ibuprofen 200 mg and acetaminphen 650 mg<br>* For morning appliance placement: dose #1 at approximately 9:00 a.m. as appointment starts; dose #2 6 hours later (3:00 p.m- or as soon after school and close to 3 pm as possible.); dose #3 another 6 hours later (9:00 p.m.); dose #4 the following morning upon waking (approximately 24 hours from start and patient will record the time), doses #5 through #7 will be taken every morning upon waking on the second, third, and fourth days, respectively. For afternoon appliance placement: dose #1 at approximately 2:00 p.m. as appointment starts; dose #2 6 hours later (8:00 p.m.); dose #3 the following morning upon waking (approximately 12 hours later and patient will record the time); dose #4 6 hours later from dose #3 (approximately 24 hours from the initial dose) around 2:00 p.m. (or as soon after school as possible) doses #5 through #7 will be taken every afternoon at 2:00 p.m. on the second, third, and fourth days, respectively.<br>|
| Placebo Comparator: Placebo<br>3 tablets of tableting compounds with no active ingredients | Drug: Placebo oral tablet<br>* For morning appliance placement: dose #1 at approximately 9:00 a.m. as appointment starts; dose #2 6 hours later (3:00 p.m- or as soon after school and close to 3 pm as possible.); dose #3 another 6 hours later (9:00 p.m.); dose #4 the following morning upon waking (approximately 24 hours from start and patient will record the time), doses #5 through #7 will be taken every morning upon waking on the second, third, and fourth days, respectively. For afternoon appliance placement: dose #1 at approximately 2:00 p.m. as appointment starts; dose #2 6 hours later (8:00 p.m.); dose #3 the following morning upon waking (approximately 12 hours later and patient will record the time); dose #4 6 hours later from dose #3 (approximately 24 hours from the initial dose) around 2:00 p.m. (or as soon after school as possible) doses #5 through #7 will be taken every afternoon at 2:00 p.m. on the second, third, and fourth days, respectively.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in visual analogue score (VAS) over time | Primary outcomes with be the pain values recorded by subjects when chewing on the 100-mm VAS at set times.The VAS line for each time period will be 100 mm long with no intermediate delineations. Each end will be marked with no pain on the left, and worst possible pain on the right. | 0 hours, 6 hours, 12 hours, and 24 hours, 48 hours, 72 hours, and 96 hours after placement of appliances | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dosing Compliance | The VAS containing booklet will ask the patient to record if he or she took all of the pills provided at each time point to monitor compliance. Additionally, the VAS containing booklet will ask the patient to record will ask if any additional medication was taken and if so, to name the additional medication and dosage. | to be recorded at 0 hours, 6 hours, 12 hours, and 24 hours, 48 hours, 72 hours, and 96 hours after placement of appliances. |