A Comparison of Postoperative Tramadol Versus Acetaminophen With Codeine in Children Undergoing Tonsillectomy - Full Text View

Purpose

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	Intervention	Phase
Tonsillitis Pain	Drug: Codeine with acetaminophen Drug: Tramadol suspension	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Comparison of Postoperative Tramadol Versus Acetaminophen With Codeine in Children Undergoing Tonsillectomy

Resource links provided by NLM:

MedlinePlus related topics: Tonsils and Adenoids

Drug Information available for: Codeine Acetaminophen Tramadol

U.S. FDA Resources

Further study details as provided by Children's Hospitals and Clinics of Minnesota:

Primary Outcome Measures:

Compare the efficacy of two different liquid pain medications: tramadol vs. codeine/acetaminophen (the current standard) during the post-tonsillectomy recovery period. [ Time Frame: Efficacy will be assessed daily during the 10-day postoperative recovery period. ] [ Designated as safety issue: No ]
Staff and caregivers will administer pain and symptom scales to capture multiple domains of acute pain.

Secondary Outcome Measures:

Compare side effects of two different pain medications (tramadol vs. codeine/acetaminophen) 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. ] [ Designated as safety issue: Yes ]

Enrollment:	85
Study Start Date:	January 2011
Study Completion Date:	May 2012
Primary Completion Date:	May 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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 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

Eligibility

Ages Eligible for Study:	4 Years to 15 Years
Genders Eligible for Study:	Both
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, AST/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

Please refer to this study by its ClinicalTrials.gov identifier: 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:

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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. No abstract available.

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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. 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.

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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. 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.

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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.

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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. 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
Study First Received:	December 23, 2010
Last Updated:	June 11, 2012
Health Authority:	United States: Institutional Review Board

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
Codeine
Tramadol
Antipyretics
Physiological Effects of Drugs

Pharmacologic Actions
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses
Analgesics, Opioid
Central Nervous System Depressants
Antitussive Agents
Respiratory System Agents
Narcotics

ClinicalTrials.gov processed this record on June 18, 2013