A Comparison of Postoperative Tramadol Versus Acetaminophen With Codeine in Children Undergoing Tonsillectomy

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ClinicalTrials.gov Identifier: NCT01267136

Recruitment Status : Completed

First Posted : December 28, 2010

Results First Posted : April 17, 2014

Last Update Posted : April 17, 2014

Sponsor:

Information provided by (Responsible Party):

Children's Hospitals and Clinics of Minnesota

Study Description

Brief Summary:

Tonsillectomy is the most common pediatric surgical procedure performed in the US. The postoperative period can be particularly painful. Codeine (usually in mixed formulation with acetaminophen) is the most commonly prescribed opioid in the US. However, evolving data questions its ability to provide optimal pain relief, while avoiding side effects, especially in the postoperative setting. Tramadol may be a better option for children in the postoperative setting due to its well-documented analgesic properties, low potential for side effects, and excellent safety profile. Seventy-two children scheduled to undergo tonsillectomy (with or without adenoidectomy) at Children's will be invited to participate in a randomized, prospective, double-blinded study to evaluate the efficacy and side effects of codeine with acetaminophen versus tramadol. Using a 10-day take-home diary, caregivers will be asked to record daily information about their child's postoperative pain and other core outcomes and domains as recommended in the recent consensus statement put forth by the Pediatric Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) (McGrath et al., 2008). This study will offer new information regarding the efficacy and side effects associated with tramadol as compared with codeine/acetaminophen (the current practice standard) in a pediatric population.

Hypotheses

H1: Children who receive scheduled tramadol following tonsillectomy will report better pain control than children who receive scheduled codeine/acetaminophen.

H2: Children who receive scheduled tramadol following tonsillectomy will report fewer side effects than children who receive scheduled codeine/acetaminophen.

Condition or disease	Intervention/treatment	Phase
Tonsillitis Pain	Drug: Codeine with acetaminophen Drug: Tramadol suspension	Phase 4

Study Design


Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	84 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	A Comparison of Postoperative Tramadol Versus Acetaminophen With Codeine in Children Undergoing Tonsillectomy
Study Start Date :	January 2011
Actual Primary Completion Date :	May 2012
Actual Study Completion Date :	May 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Tonsillitis

Drug Information available for: Codeine Acetaminophen Tramadol

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Capital® with Codeine Suspension	Drug: Codeine with acetaminophen Liquid codeine/acetaminophen (Capital® 5mL= 120mg acetaminophen/12 mg codeine) 0.72 mg/kg [=0.3 mL/kg] (max. 36 mg) PO Q6h, plus 0.72 mg/kg (max. 36 mg) PO Q3h pro re nata (PRN) (max. of 3 PRN doses/day) Other Names: Capital® with Codeine Suspension Acetaminophen and Codeine phosphate suspension
Active Comparator: Tramadol suspension	Drug: Tramadol suspension Liquid tramadol 1.05 mg/kg [=0.3 mL/kg] (max. 52.5 mg) PO Q6h, plus 1.05 mg/kg (max. 52.5 mg) PO Q3h PRN (max. of 3 PRN doses/day). Other Names: tramadol hydrochloride Ultram

Outcome Measures

Primary Outcome Measures :

Efficacy of Two Different Liquid Pain Medications: Tramadol vs. Codeine/Acetaminophen During the Post-tonsillectomy Recovery Period. [ Time Frame: Efficacy was assessed daily during the 10-day postoperative recovery period. ]
Average number of post-operative days with pain score >4/10. Pain score assessments were administered once daily by parents using either the Numeric Rating Scale (NRS-11) (with anchors 0=no pain and 10=highest pain imaginable) for children ages 8-15 (von Baeyer et al., 2009) or the Faces Pain Scale-Revised (FPS-R) (with anchors 0=no pain and 10=highest pain imaginable) for children ages 4-10 (Hicks et al., 2001).

Secondary Outcome Measures :

Number of Participants Reporting Side Effects During the Post-tonsillectomy Recovery Period. [ Time Frame: Side effects will be observed and recorded daily by caregivers for a total of 10 days in the take-home diary. ]
Parent-reported side effects entered in 10-day diary.

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	4 Years to 15 Years (Child)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Child must be scheduled to undergo tonsillectomy (with or without adenoidectomy).
Child must be between the ages of 4 and 15 at the time of enrollment.
Child and caregiver must be English-speaking.
The same caregiver (e.g., mother) must agree to complete all study assessments with child to ensure consistency.

Exclusion Criteria:

Child cannot self-assess pain due to conditions such as developmental delays, chromosomal abnormalities, and other syndromes.
Child had significant adverse effects to codeine, tramadol, or acetaminophen in the past.
Child has a known underlying seizure disorder (not febrile seizure).
Child has known underlying renal or liver dysfunction (with creatinine, aspartate aminotransferase [AST]/amino alanine transferase [ALT], above normal value for age, respectively).
Child or caregiver is not English-speaking.
The same caregiver (e.g., mother) is unable to complete all follow-up assessments.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01267136

Locations


United States, Minnesota
Children's Hospitals and Clinics of Minnesota
Minneapolis, Minnesota, United States, 55404

Sponsors and Collaborators

Children's Hospitals and Clinics of Minnesota

Investigators


Principal Investigator:	Stefan J Friedrichsdorf, M.D.	Children's Hospitals and Clinics of Minnesota

More Information

Publications:

Atef A, Fawaz AA. Peritonsillar infiltration with tramadol improves pediatric tonsillectomy pain. Eur Arch Otorhinolaryngol. 2008 May;265(5):571-4. Epub 2007 Oct 17.

Bamigbade TA, Langford, RM. The clinical use of tramadol hydrochloride Pain Rev 1998;5 155-82.

Chambers CT, Finley GA, McGrath PJ, Walsh TM. The parents' postoperative pain measure: replication and extension to 2-6-year-old children. Pain. 2003 Oct;105(3):437-43.

Chambers CT, Reid GJ, McGrath PJ, Finley GA. Development and preliminary validation of a postoperative pain measure for parents. Pain. 1996 Dec;68(2-3):307-13.

Chu YC, Lin SM, Hsieh YC, Chan KH, Tsou MY. Intraoperative administration of tramadol for postoperative nurse-controlled analgesia resulted in earlier awakening and less sedation than morphine in children after cardiac surgery. Anesth Analg. 2006 Jun;102(6):1668-73.

Ciszkowski C, Madadi P, Phillips MS, Lauwers AE, Koren G. Codeine, ultrarapid-metabolism genotype, and postoperative death. N Engl J Med. 2009 Aug 20;361(8):827-8. doi: 10.1056/NEJMc0904266.

Clark E, Plint AC, Correll R, Gaboury I, Passi B. A randomized, controlled trial of acetaminophen, ibuprofen, and codeine for acute pain relief in children with musculoskeletal trauma. Pediatrics. 2007 Mar;119(3):460-7. Erratum in: Pediatrics. 2007 Jun;119(6):1271.

Desmeules JA. The tramadol option. Eur J Pain. 2000;4 Suppl A:15-21. Review.

Dorn MT FN, Quinn FB. Tonsillitis, Tonsillectomy, and Adenoidectomy. Grand Rounds, UTMB - Department of Otolaryngology. December 1999.

Drake A CM. Tonsillectomy. EMedicine2003. Available at: http://www.emedicine.com/ent/topic315.htm.

Drendel AL, Gorelick MH, Weisman SJ, Lyon R, Brousseau DC, Kim MK. A randomized clinical trial of ibuprofen versus acetaminophen with codeine for acute pediatric arm fracture pain. Ann Emerg Med. 2009 Oct;54(4):553-60. doi: 10.1016/j.annemergmed.2009.06.005. Epub 2009 Aug 19.

Engelhardt T, Steel E, Johnston G, Veitch DY. Tramadol for pain relief in children undergoing tonsillectomy: a comparison with morphine. Paediatr Anaesth. 2003 Mar;13(3):249-52.

Finkel JC, Rose JB, Schmitz ML, Birmingham PK, Ulma GA, Gunter JB, Cnaan A, Coté CJ, Medve RA, Schreiner MS. An evaluation of the efficacy and tolerability of oral tramadol hydrochloride tablets for the treatment of postsurgical pain in children. Anesth Analg. 2002 Jun;94(6):1469-73, table of contents.

Fortier MM, J; Martin, S; Kain, Z. Children's pain at home following ambulatory surgery. J Pain2009;10(4 (Suppl1)):106.

Hain RD, Miser A, Devins M, Wallace WH. Strong opioids in pediatric palliative medicine. Paediatr Drugs. 2005;7(1):1-9. Review.

Hicks CL, von Baeyer CL, Spafford PA, van Korlaar I, Goodenough B. The Faces Pain Scale-Revised: toward a common metric in pediatric pain measurement. Pain. 2001 Aug;93(2):173-83.

Hullett BJ, Chambers NA, Pascoe EM, Johnson C. Tramadol vs morphine during adenotonsillectomy for obstructive sleep apnea in children. Paediatr Anaesth. 2006 Jun;16(6):648-53.

Marquardt KA, Alsop JA, Albertson TE. Tramadol exposures reported to statewide poison control system. Ann Pharmacother. 2005 Jun;39(6):1039-44. Epub 2005 May 3.

McGrath PA, Seifert CE, Speechley KN, Booth JC, Stitt L, Gibson MC. A new analogue scale for assessing children's pain: an initial validation study. Pain. 1996 Mar;64(3):435-43.

McGrath PJ, Walco GA, Turk DC, Dworkin RH, Brown MT, Davidson K, Eccleston C, Finley GA, Goldschneider K, Haverkos L, Hertz SH, Ljungman G, Palermo T, Rappaport BA, Rhodes T, Schechter N, Scott J, Sethna N, Svensson OK, Stinson J, von Baeyer CL, Walker L, Weisman S, White RE, Zajicek A, Zeltzer L; PedIMMPACT. Core outcome domains and measures for pediatric acute and chronic/recurrent pain clinical trials: PedIMMPACT recommendations. J Pain. 2008 Sep;9(9):771-83. doi: 10.1016/j.jpain.2008.04.007. Epub 2008 Jun 17.

McLellan RA, Oscarson M, Seidegård J, Evans DA, Ingelman-Sundberg M. Frequent occurrence of CYP2D6 gene duplication in Saudi Arabians. Pharmacogenetics. 1997 Jun;7(3):187-91.

Moir MS, Bair E, Shinnick P, Messner A. Acetaminophen versus acetaminophen with codeine after pediatric tonsillectomy. Laryngoscope. 2000 Nov;110(11):1824-7.

Moore A, Collins S, Carroll D, McQuay H. Paracetamol with and without codeine in acute pain: a quantitative systematic review. Pain. 1997 Apr;70(2-3):193-201. Review.

Moore RA, McQuay HJ. Single-patient data meta-analysis of 3453 postoperative patients: oral tramadol versus placebo, codeine and combination analgesics. Pain. 1997 Feb;69(3):287-94.

Nunez DA, Provan J, Crawford M. Postoperative tonsillectomy pain in pediatric patients: electrocautery (hot) vs cold dissection and snare tonsillectomy--a randomized trial. Arch Otolaryngol Head Neck Surg. 2000 Jul;126(7):837-41.

Oxford Pain Site. Available at: http://www.medicine.oc.ac.uk/bandolier/booth/painpag/acute.html

Pendeville PE, Von Montigny S, Dort JP, Veyckemans F. Double-blind randomized study of tramadol vs. paracetamol in analgesia after day-case tonsillectomy in children. Eur J Anaesthesiol. 2000 Sep;17(9):576-82.

Rose JB, Finkel JC, Arquedas-Mohs A, Himelstein BP, Schreiner M, Medve RA. Oral tramadol for the treatment of pain of 7-30 days' duration in children. Anesth Analg. 2003 Jan;96(1):78-81, table of contents.

Sidman JD, Lander TA, Finkelstein M. Platelet-rich plasma for pediatric tonsillectomy patients. Laryngoscope. 2008 Oct;118(10):1765-7. doi: 10.1097/MLG.0b013e31817f18e7.

Sutters KA, Miaskowski C, Holdridge-Zeuner D, Waite S, Paul SM, Savedra MC, Lanier B. Time-contingent dosing of an opioid analgesic after tonsillectomy does not increase moderate-to-severe side effects in children. Pain Manag Nurs. 2005 Jun;6(2):49-57.

von Baeyer CL, Spagrud LJ, McCormick JC, Choo E, Neville K, Connelly MA. Three new datasets supporting use of the Numerical Rating Scale (NRS-11) for children's self-reports of pain intensity. Pain. 2009 Jun;143(3):223-7. doi: 10.1016/j.pain.2009.03.002. Epub 2009 Apr 8.

Williams DG, Patel A, Howard RF. Pharmacogenetics of codeine metabolism in an urban population of children and its implications for analgesic reliability. Br J Anaesth. 2002 Dec;89(6):839-45.


Responsible Party:	Children's Hospitals and Clinics of Minnesota
ClinicalTrials.gov Identifier:	NCT01267136 History of Changes
Other Study ID Numbers:	1010-086
First Posted:	December 28, 2010 Key Record Dates
Results First Posted:	April 17, 2014
Last Update Posted:	April 17, 2014
Last Verified:	March 2014

Keywords provided by Children's Hospitals and Clinics of Minnesota:


Tonsillectomy Pain Pediatric	Opioids Tramadol Codeine

Additional relevant MeSH terms:


Tonsillitis Pharyngitis Pharyngeal Diseases Stomatognathic Diseases Respiratory Tract Infections Respiratory Tract Diseases Otorhinolaryngologic Diseases Acetaminophen Tramadol Codeine Analgesics, Non-Narcotic	Analgesics Sensory System Agents Peripheral Nervous System Agents Physiological Effects of Drugs Antipyretics Analgesics, Opioid Narcotics Central Nervous System Depressants Antitussive Agents Respiratory System Agents

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