Clinical trial NCT04059172: Efficacy of Combined Ibuprofen and Acetaminophen Therapy Versus Ibuprofen Alone Versus Placebo Alone for Pain Management
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Pain, Orofacial
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
First posted: 2019-08-16
Enrollment: 375
Sex: ALL
Minimum age (years): 12
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Two investigational groups and a placebo group
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in visual analogue score (VAS) over time
timeFrame: 0 hours, 6 hours, 12 hours, and 24 hours, 48 hours, 72 hours, and 96 hours after placement of appliances
Secondary outcomes:
measure: Dosing Compliance
timeFrame: to be recorded at 0 hours, 6 hours, 12 hours, and 24 hours, 48 hours, 72 hours, and 96 hours after placement of appliances.
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado, School of Dental Medicine
state: Colorado
Study officials:
References:
citation: 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.
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.
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.
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.
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.
citation: Romsing J, Moiniche S, Dahl JB. Rectal and parenteral paracetamol, and paracetamol in combination with NSAIDs, for postoperative analgesia. Br J Anaesth. 2002 Feb;88(2):215-26. doi: 10.1093/bja/88.2.215.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
citation: 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.
citation: Wilson S, Ngan P, Kess B. Time course of the discomfort in young patients undergoing orthodontic treatment. Pediatr Dent. 1989 Jun;11(2):107-10.