TonsillitisPhase 4NCT01267136
A Comparison of Postoperative Tramadol Versus Acetaminophen With Codeine in Children Undergoing Tonsillectomy
A Phase 4 study testing Codeine with acetaminophen and Tramadol suspension in people with Tonsillitis and Pain, run by Children's Hospitals and Clinics of Minnesota at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 4 to 15 years
- Conditions the study is for
- Tonsillitis, Pain
- What is being tested?
- Codeine with acetaminophen and Tramadol suspension
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 84 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2011to May 2012
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 15 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Hospitals and Clinics of Minnesota
Minneapolis, Minnesota, 55404
About this study
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
Read more
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.
- Conditions
- Tonsillitis, Pain
- Being tested
- Codeine with acetaminophen, Tramadol suspension
- Keywords
- Tonsillectomy, Pain, Pediatric, Opioids, Tramadol, Codeine
- Medical subject headings
- Tonsillitis, Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Codeine with acetaminophenDrug
Also called Capital® with Codeine Suspension, Acetaminophen and Codeine phosphate suspension
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)
Tramadol suspensionDrug
Also called tramadol hydrochloride, Ultram
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).
| Study group | Role | What they receive |
|---|---|---|
| Capital® with Codeine Suspension | Experimental | Not described Receives: Drug: Codeine with acetaminophen |
| Tramadol suspension | Active comparator | Not described Receives: Drug: Tramadol suspension |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Efficacy was assessed daily during the 10-day postoperative recovery period.
Secondary outcomes (1)
Number of Participants Reporting Side Effects During the Post-tonsillectomy Recovery Period.
Parent-reported side effects entered in 10-day diary.
Measured: Side effects will be observed and recorded daily by caregivers for a total of 10 days in the take-home diary.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Dec 2010 (estimated)
- Study startJan 2011
- Primary completionMay 2012
- Study completionMay 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (32)Papers the sponsor has linked to this study.
- Other trials for TonsillitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 84 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospitals and Clinics of Minnesota
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Stefan J Friedrichsdorf, M.D., Principal investigator, Children's Hospitals and Clinics of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01267136
- Sponsor's protocol ID
- 1010-086
- Status last verified
- Mar 2014
- First submitted
- 23 Dec 2010
- Last updated
- 17 Apr 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Atef A, Fawaz AA. Peritonsillar infiltration with tramadol improves pediatric tonsillectomy pain. Eur Arch Otorhinolaryngol. 2008 May;265(5):571-4. doi: 10.1007/s00405-007-0479-6. Epub 2007 Oct 17.
PubMed 17940786Bamigbade TA, Langford RM. Tramadol hydrochloride: an overview of current use. Hosp Med. 1998 May;59(5):373-6.
PubMed 9722388Chambers CT, Finley AG, McGrath PJ, Walsh TM. The parents' postoperative pain measure: replication and extension to 2-6-year-old children. Pain. 2003 Oct;105(3):437-443. doi: 10.1016/S0304-3959(03)00256-2.
PubMed 14527704Chambers 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. doi: 10.1016/s0304-3959(96)03209-5.
PubMed 9121819Chu 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. doi: 10.1213/01.ANE.0000219587.02263.A0.
PubMed 16717306Ciszkowski 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. No abstract available.
PubMed 19692698Clark 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. doi: 10.1542/peds.2006-1347.
PubMed 17332198Desmeules JA. The tramadol option. Eur J Pain. 2000;4 Suppl A:15-21.
PubMed 11310478Dorn 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.
PubMed 19692147Engelhardt 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. doi: 10.1046/j.1460-9592.2003.00983.x.
PubMed 12641688Finkel JC, Rose JB, Schmitz ML, Birmingham PK, Ulma GA, Gunter JB, Cnaan A, Cote 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. doi: 10.1097/00000539-200206000-00017.
PubMed 12032009Fortier 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. doi: 10.2165/00148581-200507010-00001.
PubMed 15777107
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Comparison of Postoperative Tramadol Versus Acetaminophen With Codeine in Children Undergoing Tonsillectomy
- ClinicalTrials.gov ID
- NCT01267136
- Acronym / sponsor ID
- 1010-086
- Conditions
- Tonsillitis, Pain
- Keywords
- Tonsillectomy, Pain, Pediatric, Opioids, Tramadol, Codeine
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 84 participants (actual)
- Lead sponsor
- Children's Hospitals and Clinics of MinnesotaUniversity, hospital or other
- Study start
- Jan 2011
- Primary completion
- May 2012 (actual)
- Study completion
- May 2012 (actual)
- First posted
- 28 Dec 2010 (estimated)
- Results
- Posted 17 Apr 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Capital® with Codeine Suspension | Experimental | Drug: Codeine with acetaminophen |
| Tramadol suspension | Active comparator | Drug: Tramadol suspension |
Who may qualify
- Ages
- 4 to 15 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Codeine with acetaminophenAlso: Capital® with Codeine Suspension, Acetaminophen and Codeine phosphate suspensionLiquid 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) | Drug | Capital® with Codeine Suspension |
| Tramadol suspensionAlso: tramadol hydrochloride, UltramLiquid 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). | Drug | Tramadol suspension |
Primary outcome
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).
1 secondary outcome
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 17940786Atef A, Fawaz AA. Peritonsillar infiltration with tramadol improves pediatric tonsillectomy pain. Eur Arch Otorhinolaryngol. 2008 May;265(5):571-4. doi: 10.1007/s00405-007-0479-6. Epub 2007 Oct 17.
- Background: PubMed 9722388Bamigbade TA, Langford RM. Tramadol hydrochloride: an overview of current use. Hosp Med. 1998 May;59(5):373-6.
- Background: PubMed 14527704Chambers CT, Finley AG, McGrath PJ, Walsh TM. The parents' postoperative pain measure: replication and extension to 2-6-year-old children. Pain. 2003 Oct;105(3):437-443. doi: 10.1016/S0304-3959(03)00256-2.
- Background: PubMed 9121819Chambers 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. doi: 10.1016/s0304-3959(96)03209-5.
- Background: PubMed 16717306Chu 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. doi: 10.1213/01.ANE.0000219587.02263.A0.
- Background: PubMed 19692698Ciszkowski 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. No abstract available.
- Background: PubMed 17332198Clark 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. doi: 10.1542/peds.2006-1347.
- Background: PubMed 11310478Desmeules JA. The tramadol option. Eur J Pain. 2000;4 Suppl A:15-21.
- BackgroundDorn MT FN, Quinn FB. Tonsillitis, Tonsillectomy, and Adenoidectomy. Grand Rounds, UTMB - Department of Otolaryngology. December 1999.
- BackgroundDrake A CM. Tonsillectomy. EMedicine2003. Available at: http://www.emedicine.com/ent/topic315.htm.
- Background: PubMed 19692147Drendel 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.
- Background: PubMed 12641688Engelhardt 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. doi: 10.1046/j.1460-9592.2003.00983.x.
Related trials for Tonsillitis
RecruitingPhase 4
A Single Dose of Intravenous Penicillin as an Adjunct to Oral Penicillin in the Treatment of Acute Tonsillitis, Peritonsillar Phlegmon, and Peritonsillar Abscess
Acute Tonsillitis, Peritonsillar Abscess
Recruiting
Perspectives on Antibiotics and Tracking Symptoms in Children
Urinary Tract Infection, Cellulitis
Recruiting
Suprazygomatic Maxillary Nerve Block in Pediatric Tonsillectomy
Tonsillitis
Active, not recruiting
Tonsillectomy Versus Tonsillotomy in the Treatment of Recurrent Acute Tonsillitis
Tonsillitis Recurrent
Recruiting
Transoral Ultrasound Versus no Transoral Ultrasound in Diagnostic Workup of Peritonsillar Abscess
Peritonsillar Abscess, Peritonsillar Cellulitis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stefan J Friedrichsdorf, M.D. principal investigator
Children's Hospitals and Clinics of Minnesota
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Codeine with acetaminophen and Tramadol suspension in people with Tonsillitis and Pain, run by Children's Hospitals and Clinics of Minnesota at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Apr 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Apr 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01267136, which also lists 32 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2014.