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

Pain, Orofacial Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04059172
• Other study ID #: 17-1449
• Status: Recruiting
• Phase: Early Phase 1
• Start date: December 10, 2019
• Est. completion date: March 1, 2025

Study information

• Verified date: November 2023
• Source: University of Colorado, Denver
• Contact: Clifton M Carey, PhD
• Phone: 3037241046
• Email: clifton.carey[@]cuanschutz.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 375
• Est. completion date: March 1, 2025
• Est. primary completion date: March 1, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 12 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Facial Pain
• Pain, Orofacial

Intervention

Drug:
• Ibuprofen 200 mg and acetaminphen 650 mg
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.
• Ibuprofen 200 mg
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.
• Placebo oral tablet
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.

Locations

Country	Name	City	State
United States	University of Colorado, School of Dental Medicine	Aurora	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
University of Colorado, Denver

Country where clinical trial is conducted

United States, 

References & Publications (20)

Angelopoulou MV, Vlachou V, Halazonetis DJ. Pharmacological management of pain during orthodontic treatment: a meta-analysis. Orthod Craniofac Res. 2012 May;15(2):71-83. doi: 10.1111/j.1601-6343.2012.01542.x. — View Citation

Bartzela T, Turp JC, Motschall E, Maltha JC. Medication effects on the rate of orthodontic tooth movement: a systematic literature review. Am J Orthod Dentofacial Orthop. 2009 Jan;135(1):16-26. doi: 10.1016/j.ajodo.2008.08.016. — View Citation

Bernhardt MK, Southard KA, Batterson KD, Logan HL, Baker KA, Jakobsen JR. The effect of preemptive and/or postoperative ibuprofen therapy for orthodontic pain. Am J Orthod Dentofacial Orthop. 2001 Jul;120(1):20-7. doi: 10.1067/mod.2001.115616. — View Citation

Doll GM, Zentner A, Klages U, Sergl HG. Relationship between patient discomfort, appliance acceptance and compliance in orthodontic therapy. J Orofac Orthop. 2000;61(6):398-413. doi: 10.1007/pl00001908. English, German. — View Citation

Hyllested M, Jones S, Pedersen JL, Kehlet H. Comparative effect of paracetamol, NSAIDs or their combination in postoperative pain management: a qualitative review. Br J Anaesth. 2002 Feb;88(2):199-214. doi: 10.1093/bja/88.2.199. — View Citation

Jones M, Chan C. The pain and discomfort experienced during orthodontic treatment: a randomized controlled clinical trial of two initial aligning arch wires. Am J Orthod Dentofacial Orthop. 1992 Oct;102(4):373-81. doi: 10.1016/0889-5406(92)70054-e. — View Citation

Jones ML, Chan C. Pain in the early stages of orthodontic treatment. J Clin Orthod. 1992 May;26(5):311-3. No abstract available. — View Citation

Lamberton JA, Oesterle LJ, Shellhart WC, Newman SM, Harrell RE, Tilliss T, Singh N, Carey CM. Comparison of pain perception during miniscrew placement in orthodontic patients with a visual analog scale survey between compound topical and needle-injected anesthetics: A crossover, prospective, randomized clinical trial. Am J Orthod Dentofacial Orthop. 2016 Jan;149(1):15-23. doi: 10.1016/j.ajodo.2015.08.013. — View Citation

Minor V, Marris CK, McGorray SP, Yezierski R, Fillingim R, Logan H, Wheeler TT. Effects of preoperative ibuprofen on pain after separator placement. Am J Orthod Dentofacial Orthop. 2009 Oct;136(4):510-7. doi: 10.1016/j.ajodo.2007.09.018. — View Citation

Ngan P, Wilson S, Shanfeld J, Amini H. The effect of ibuprofen on the level of discomfort in patients undergoing orthodontic treatment. Am J Orthod Dentofacial Orthop. 1994 Jul;106(1):88-95. doi: 10.1016/S0889-5406(94)70025-7. — View Citation

Ohnhaus EE, Adler R. Methodological problems in the measurement of pain: a comparison between the verbal rating scale and the visual analogue scale. Pain. 1975 Dec;1(4):379-384. doi: 10.1016/0304-3959(75)90075-5. — View Citation

Oliver RG, Knapman YM. Attitudes to orthodontic treatment. Br J Orthod. 1985 Oct;12(4):179-88. doi: 10.1179/bjo.12.4.179. — View Citation

Ong CK, Seymour RA, Lirk P, Merry AF. Combining paracetamol (acetaminophen) with nonsteroidal antiinflammatory drugs: a qualitative systematic review of analgesic efficacy for acute postoperative pain. Anesth Analg. 2010 Apr 1;110(4):1170-9. doi: 10.1213/ANE.0b013e3181cf9281. Epub 2010 Feb 8. — View Citation

Ottoson D, Ekblom A, Hansson P. Vibratory stimulation for the relief of pain of dental origin. Pain. 1981 Feb;10(1):37-45. doi: 10.1016/0304-3959(81)90043-9. — View Citation

Polat O, Karaman AI, Durmus E. Effects of preoperative ibuprofen and naproxen sodium on orthodontic pain. Angle Orthod. 2005 Sep;75(5):791-6. doi: 10.1043/0003-3219(2005)75[791:EOPIAN]2.0.CO;2. Erratum In: Angle Orthod. 2008 Nov;78(6):976. Angle Orthod. 2008 Sep;78(5):798. — View Citation

Price DD, McGrath PA, Rafii A, Buckingham B. The validation of visual analogue scales as ratio scale measures for chronic and experimental pain. Pain. 1983 Sep;17(1):45-56. doi: 10.1016/0304-3959(83)90126-4. — View Citation

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Salmassian R, Oesterle LJ, Shellhart WC, Newman SM. Comparison of the efficacy of ibuprofen and acetaminophen in controlling pain after orthodontic tooth movement. Am J Orthod Dentofacial Orthop. 2009 Apr;135(4):516-21. doi: 10.1016/j.ajodo.2007.05.020. — View Citation

Steen Law SL, Southard KA, Law AS, Logan HL, Jakobsen JR. An evaluation of preoperative ibuprofen for treatment of pain associated with orthodontic separator placement. Am J Orthod Dentofacial Orthop. 2000 Dec;118(6):629-35. doi: 10.1067/mod.2000.110638. — View Citation

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* Note: There are 20 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.