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

Study Overview
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Brief Summary
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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.

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

Conditions
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Tonsillitis, Pain

Intervention / Treatment
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* Drug: Codeine with acetaminophen
* Drug: Tramadol suspension


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 15 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Capital® with Codeine Suspension<br> | Drug: Codeine with acetaminophen<br>* 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)<br>* Other names: Acetaminophen and Codeine phosphate suspension;|
| Active Comparator: Tramadol suspension<br> | Drug: Tramadol suspension<br>* 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).<br>* Other names: Ultram;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of Two Different Liquid Pain Medications: Tramadol vs. Codeine/Acetaminophen During the Post-tonsillectomy 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). | Efficacy was assessed daily during the 10-day postoperative recovery period. | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tonsillectomy, Pain, Pediatric, Opioids, Tramadol, Codeine