AdenotonsillitisPhase 2NCT01691690
Analgesic Effect of IV Acetaminophen in Tonsillectomies
A Phase 2 study testing Acetaminophen (paracetamol), Normal Saline Flush and Midazolam in people with Adenotonsillitis and Tonsillitis, run by Nationwide Children's Hospital at 1 site in United States.
Trial summary
Acetaminophen (paracetamol) is a first-line antipyretic and analgesic for mild and moderate pain for pediatric patients. Its common use (particularly in oral form) is underscored by its wide therapeutic window, safety profile, over the counter accessibility, lack of adverse systemic effects (as compared with NSAIDS… Read more about this study
- Who is it for?
- Ages 2 to 9 years
- Conditions the study is for
- Adenotonsillitis, Tonsillitis
- What is being tested?
- Acetaminophen (paracetamol), Normal Saline Flush and Midazolam
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 250 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2012to Jul 2016
- Phase
- Phase 2
- 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 2 to 9 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Male or female patients aged 2 years and younger than 9 years old requiring postoperative admission for tonsillectomy or adenotonsillectomy.
- Functional status as assigned by the American Society of Anesthesiology (ASA) classification of I (1), II (2) or III (3).
- Have a parent/guardian who are able to provide written informed consent in accordance with Human Investigations Committee/Institutional Review Board (HIC/IRB) regulations.
- Have parent/guardian who are compliant with routine medical care, capable of subjective evaluation and able to read, understand and sign the informed consent.
Who cannot join
- Male or female patients age greater than 9 years.
- Have an American Society of Anesthesiologists Physical Status > IV (4)(severe disease that is life threatening).
- Have a known hypersensitivity or allergy to acetaminophen.
- Have a known allergy or intolerance to morphine or fentanyl.
- Have received chronic opioid analgesic therapy prior to surgery.
- Have renal disease.
- Have hepatic disease.
- Are morbidly obese (% BMI > 95).
Trial locations and contacts
1 site in 1 country.
United States1 site
Nationwide Children's Hospital
Columbus, Ohio, 43205
About this study
Official title: Analgesic Effect of Single Dose Intravenous Acetaminophen in Pediatric Patients Undergoing Tonsillectomy
Acetaminophen (paracetamol) is a first-line antipyretic and analgesic for mild and moderate pain for pediatric patients. Its common use (particularly in oral form) is underscored by its wide therapeutic window, safety profile, over the counter accessibility, lack of adverse systemic effects (as compared with NSAIDS and opioids) when given in appropriate doses.
Although the exact anti-nociceptive mechanisms of acetaminophen continue to be elucidated, these mechanisms appear to be multi-factorial and include central inhibition of the cyclo-oxygenase (COX) enzyme leading to decreased production of prostaglandins from arachidonic acid, interference with serotonergic descending pain pathways, indirect activation of cannabinoid 1 (CB1) receptors and inhibition of nitric oxide pathways through N-methyl-D-aspartate (NMDA) or substance P. Of the above mechanisms, the most commonly known is that of central inhibition of COX enzymes by which the decreased production of prostaglandins diminish the release of excitatory transmitters of substance P and glutamate which are both involved in nociceptive transmission (Anderson, 2008; Smith, 2011).
To date, several studies have shown acetaminophen's opioid sparing effect in the pediatric population when given by the rectal or intravenous routes (Korpela et al, 1999; Dashti et al, 2009; Hong et al, 2010).
Read the detailed description
Once enrolled, subjects will have a standardized anesthetic on the day of surgery:
- Pre-medication with oral midazolam (0.5mg/kg to maximum dose of 20mg) given 15-20 minutes before induction
- Inhalation induction with sevoflurane and a mixture of N20/02
- Propofol 1-1.5 mg/kg to facilitate endotracheal intubation
- Morphine 0.1 mg/kg given prior to intubation
- Maintenance anesthesia with isoflurane, titrated to 0.8-1 Minimal Anesthetic Concentration (MAC) with a mixture of Air/02
- Acetaminophen IV (15 mg/kg) vs. saline placebo infused intraoperatively (randomized by pharmacy)
- Ondansetron (0.15 mg/kg, maximum dose of 4 mg) and dexamethasone (0.25 mg/kg, maximum dose of 20 mg) for postoperative nausea prophylaxis.
Following surgery and extubation, baseline vitals will be obtained and pain scores will be assessed in the post anesthesia care unit (PACU) via Faces, Legs, Activity, Cry, Consolability Scale (FLACC).The presence of emergence delirium will be assessed via Pediatric Agitation and Emergence Delirium scale (PAED). Those subjects whose pain score is assessed at < 4 will receive standard postoperative care and no analgesics. Assessed pain scores > 4 will receive 0.5mcg/kg fentanyl q10 minutes as needed. Variables such as time to extubation in the PACU, time to first analgesic delivery, pain scores, # times/total dose of opioids given, presence of sedation, nausea/vomiting, duration of oxygen requirement in PACU, whether or not patient was discharged to floor on oxygen and total PACU time will be recorded during the duration of the patient's PACU stay. Subjects will be discharged to the inpatient floor from the PACU once standard discharge criteria have been met.
Following discharge from the PACU, standardized analgesics will be given for breakthrough pain (oral oxycodone 0.1mg/kg q4hrs pro re nata (PRN) pain). Enrolled patients will be followed during the duration of their inpatient stay. Duration of oxygen requirement on the floor, pain scores and number of administered oxycodone doses on the floor will be monitored and recorded.
- Conditions
- Adenotonsillitis, Tonsillitis
- Being tested
- Acetaminophen (paracetamol), Normal Saline Flush, Midazolam, Sevoflurane, Nitrous Oxide/Oxygen
- Medical subject headings
- Tonsillitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Acetaminophen (paracetamol)Drug
Acetaminophen IV (15 mg/kg).
Normal Saline FlushDrug
Saline placebo will be infused intraoperatively.
MidazolamDrug
Also called Versed
Midazolam (0.5mg/kg to maximum dose of 20mg) given 15-20 minutes before induction.
SevofluraneDrug
Sevoflurane for anesthesia induction.
Nitrous Oxide/OxygenDrug
Combination of NO2 \& O2 for anesthesia induction.
PropofolDrug
Propofol 1-1.5 mg/kg to facilitate endotracheal intubation.
MorphineDrug
Morphine 0.1 mg/kg given prior to intubation.
OndansetronDrug
Also called Zofran
Ondansetron (0.15 mg/kg, maximum dose of 4 mg) for postoperative nausea prophylaxis.
DexamethasoneDrug
Dexamethasone (0.25 mg/kg, maximum dose of 20 mg) for postoperative nausea prophylaxis.
| Study group | Role | What they receive |
|---|---|---|
| IV Acetaminophen | Experimental | Patients will receive pre-medication with oral midazolam Participants of this experimental arm of the study will receive Acetaminophen IV to evaluate opioid-sparing effect and pain score reduction.. Receives: Drug: Acetaminophen (paracetamol); Drug: Midazolam; Drug: Sevoflurane; Drug: Nitrous Oxide/Oxygen; Drug: Propofol; Drug: Morphine; Drug: Ondansetron; Drug: Dexamethasone |
| Saline placebo infused intraoperatively | Placebo comparator | For this arm Morphine will be administered to manage pain. Receives: Drug: Normal Saline Flush; Drug: Midazolam; Drug: Sevoflurane; Drug: Nitrous Oxide/Oxygen; Drug: Propofol; Drug: Morphine; Drug: Ondansetron; Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
FLACC Pain Score Greater Than or Equal to 4
The Face, Legs, Activity, Cry, Consolability scale or FLACC scale is a measurement used to assess pain for children between the ages of 2 months and 7 years or individuals that are unable to communicate their pain. The scale is scored in a range of 0-10 with 0 representing no pain. 5 pain measurements were performed at 0, 5, 15, 30, and 60 minutes after PACU arrival. This is the number of participants who reached a FLACC score >/= 4 at one or more time points.
Measured: 0-60 mins post-operatively
Secondary outcomes (2)
Analgesics Administered After Arrival to Inpatient Ward and Number of Participants Requiring Each
Analgesics administered after arrival to the inpatient ward included hydrocodone/acetaminophen, oxycodone, NSAIDS, acetaminophen, and morphine.
Measured: 8-12 hours post-operatively
Time of First Opioid Analgesia in PACU
Mean time to first drug administration among patients requiring opioid analgesia in the PACU.
Measured: 0-90 minutes post-operatively
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2012 (estimated)
- Study startOct 2012
- Primary completionNov 2015
- Study completionJul 2016
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 (5)Papers the sponsor has linked to this study.
- Other trials for AdenotonsillitisStudies of the same condition, open and under way.
- More trials run by Nationwide Children's HospitalThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 250 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nationwide Children's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Arlyne Thung, Nationwide Children's Hospital
- Investigators
- Arlyne Thung, MD, Principal investigator, Nationwide Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01691690
- Sponsor's protocol ID
- IRB12-00097
- Status last verified
- Feb 2017
- First submitted
- 30 May 2012
- Last updated
- 6 Apr 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Anderson BJ. Paracetamol (Acetaminophen): mechanisms of action. Paediatr Anaesth. 2008 Oct;18(10):915-21. doi: 10.1111/j.1460-9592.2008.02764.x.
PubMed 18811827Smith HS. Perioperative intravenous acetaminophen and NSAIDs. Pain Med. 2011 Jun;12(6):961-81. doi: 10.1111/j.1526-4637.2011.01141.x. Epub 2011 May 31.
PubMed 21627768Korpela R, Korvenoja P, Meretoja OA. Morphine-sparing effect of acetaminophen in pediatric day-case surgery. Anesthesiology. 1999 Aug;91(2):442-7. doi: 10.1097/00000542-199908000-00019.
PubMed 10443608Dashti GA, Amini S, Zanguee E. The prophylactic effect of rectal acetaminophen on postoperative pain and opioid requirements after adenotonsillectomy in children. Middle East J Anaesthesiol. 2009 Jun;20(2):245-9.
PubMed 19583073Hong JY, Kim WO, Koo BN, Cho JS, Suk EH, Kil HK. Fentanyl-sparing effect of acetaminophen as a mixture of fentanyl in intravenous parent-/nurse-controlled analgesia after pediatric ureteroneocystostomy. Anesthesiology. 2010 Sep;113(3):672-7. doi: 10.1097/ALN.0b013e3181e2c34b.
PubMed 20693884
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Analgesic Effect of Single Dose Intravenous Acetaminophen in Pediatric Patients Undergoing Tonsillectomy
- ClinicalTrials.gov ID
- NCT01691690
- Acronym / sponsor ID
- IRB12-00097
- Conditions
- Adenotonsillitis, Tonsillitis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 250 participants (actual)
- Lead sponsor
- Nationwide Children's HospitalUniversity, hospital or other
- Study start
- Oct 2012
- Primary completion
- Nov 2015 (actual)
- Study completion
- Jul 2016 (actual)
- First posted
- 25 Sep 2012 (estimated)
- Results
- Posted 6 Apr 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Acetaminophen (paracetamol) is a first-line antipyretic and analgesic for mild and moderate pain for pediatric patients. Its common use (particularly in oral form) is underscored by its wide therapeutic window, safety profile, over the counter accessibility, lack of adverse systemic effects (as compared with NSAIDS and opioids) when given in appropriate doses.
Although the exact anti-nociceptive mechanisms of acetaminophen continue to be elucidated, these mechanisms appear to be multi-factorial and include central inhibition of the cyclo-oxygenase (COX) enzyme leading to decreased production of prostaglandins from arachidonic acid, interference with serotonergic descending pain pathways, indirect activation of cannabinoid 1 (CB1) receptors and inhibition of nitric oxide pathways through N-methyl-D-aspartate (NMDA) or substance P. Of the above mechanisms, the most commonly known is that of central inhibition of COX enzymes by which the decreased production of prostaglandins diminish the release of excitatory transmitters of substance P and glutamate which are both involved in nociceptive transmission (Anderson, 2008; Smith, 2011).
To date, several studies have shown acetaminophen's opioid sparing effect in the pediatric population when given by the rectal or intravenous routes (Korpela et al, 1999; Dashti et al, 2009; Hong et al, 2010).
Detailed description
Once enrolled, subjects will have a standardized anesthetic on the day of surgery:
- Pre-medication with oral midazolam (0.5mg/kg to maximum dose of 20mg) given 15-20 minutes before induction
- Inhalation induction with sevoflurane and a mixture of N20/02
- Propofol 1-1.5 mg/kg to facilitate endotracheal intubation
- Morphine 0.1 mg/kg given prior to intubation
- Maintenance anesthesia with isoflurane, titrated to 0.8-1 Minimal Anesthetic Concentration (MAC) with a mixture of Air/02
- Acetaminophen IV (15 mg/kg) vs. saline placebo infused intraoperatively (randomized by pharmacy)
- Ondansetron (0.15 mg/kg, maximum dose of 4 mg) and dexamethasone (0.25 mg/kg, maximum dose of 20 mg) for postoperative nausea prophylaxis.
Following surgery and extubation, baseline vitals will be obtained and pain scores will be assessed in the post anesthesia care unit (PACU) via Faces, Legs, Activity, Cry, Consolability Scale (FLACC).The presence of emergence delirium will be assessed via Pediatric Agitation and Emergence Delirium scale (PAED). Those subjects whose pain score is assessed at < 4 will receive standard postoperative care and no analgesics. Assessed pain scores > 4 will receive 0.5mcg/kg fentanyl q10 minutes as needed. Variables such as time to extubation in the PACU, time to first analgesic delivery, pain scores, # times/total dose of opioids given, presence of sedation, nausea/vomiting, duration of oxygen requirement in PACU, whether or not patient was discharged to floor on oxygen and total PACU time will be recorded during the duration of the patient's PACU stay. Subjects will be discharged to the inpatient floor from the PACU once standard discharge criteria have been met.
Following discharge from the PACU, standardized analgesics will be given for breakthrough pain (oral oxycodone 0.1mg/kg q4hrs pro re nata (PRN) pain). Enrolled patients will be followed during the duration of their inpatient stay. Duration of oxygen requirement on the floor, pain scores and number of administered oxycodone doses on the floor will be monitored and recorded.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| IV Acetaminophen | Experimental | Drug: Acetaminophen (paracetamol), Drug: Midazolam, Drug: Sevoflurane, Drug: Nitrous Oxide/Oxygen, Drug: Propofol, Drug: Morphine, Drug: Ondansetron, Drug: DexamethasonePatients will receive pre-medication with oral midazolam Participants of this experimental arm of the study will receive Acetaminophen IV to evaluate opioid-sparing effect and pain score reduction.. |
| Saline placebo infused intraoperatively | Placebo comparator | Drug: Normal Saline Flush, Drug: Midazolam, Drug: Sevoflurane, Drug: Nitrous Oxide/Oxygen, Drug: Propofol, Drug: Morphine, Drug: Ondansetron, Drug: DexamethasoneFor this arm Morphine will be administered to manage pain. |
Who may qualify
- Ages
- 2 to 9 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Male or female patients aged 2 years and younger than 9 years old requiring postoperative admission for tonsillectomy or adenotonsillectomy.
- Functional status as assigned by the American Society of Anesthesiology (ASA) classification of I (1), II (2) or III (3).
- Have a parent/guardian who are able to provide written informed consent in accordance with Human Investigations Committee/Institutional Review Board (HIC/IRB) regulations.
- Have parent/guardian who are compliant with routine medical care, capable of subjective evaluation and able to read, understand and sign the informed consent.
Key exclusion criteria (8 listed)
- Male or female patients age greater than 9 years.
- Have an American Society of Anesthesiologists Physical Status > IV (4)(severe disease that is life threatening).
- Have a known hypersensitivity or allergy to acetaminophen.
- Have a known allergy or intolerance to morphine or fentanyl.
- Have received chronic opioid analgesic therapy prior to surgery.
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 |
|---|---|---|
| Acetaminophen (paracetamol)Acetaminophen IV (15 mg/kg). | Drug | IV Acetaminophen |
| Normal Saline FlushSaline placebo will be infused intraoperatively. | Drug | Saline placebo infused intraoperatively |
| MidazolamAlso: VersedMidazolam (0.5mg/kg to maximum dose of 20mg) given 15-20 minutes before induction. | Drug | IV Acetaminophen, Saline placebo infused intraoperatively |
| SevofluraneSevoflurane for anesthesia induction. | Drug | IV Acetaminophen, Saline placebo infused intraoperatively |
| Nitrous Oxide/OxygenCombination of NO2 \& O2 for anesthesia induction. | Drug | IV Acetaminophen, Saline placebo infused intraoperatively |
| PropofolPropofol 1-1.5 mg/kg to facilitate endotracheal intubation. | Drug | IV Acetaminophen, Saline placebo infused intraoperatively |
| MorphineMorphine 0.1 mg/kg given prior to intubation. | Drug | IV Acetaminophen, Saline placebo infused intraoperatively |
| OndansetronAlso: ZofranOndansetron (0.15 mg/kg, maximum dose of 4 mg) for postoperative nausea prophylaxis. | Drug | IV Acetaminophen, Saline placebo infused intraoperatively |
| DexamethasoneDexamethasone (0.25 mg/kg, maximum dose of 20 mg) for postoperative nausea prophylaxis. | Drug | IV Acetaminophen, Saline placebo infused intraoperatively |
Primary outcome
FLACC Pain Score Greater Than or Equal to 4
Time frame: 0-60 mins post-operatively
The Face, Legs, Activity, Cry, Consolability scale or FLACC scale is a measurement used to assess pain for children between the ages of 2 months and 7 years or individuals that are unable to communicate their pain. The scale is scored in a range of 0-10 with 0 representing no pain. 5 pain measurements were performed at 0, 5, 15, 30, and 60 minutes after PACU arrival. This is the number of participants who reached a FLACC score >/= 4 at one or more time points.
2 secondary outcomes
Analgesics Administered After Arrival to Inpatient Ward and Number of Participants Requiring Each
Time frame: 8-12 hours post-operatively
Time of First Opioid Analgesia in PACU
Time frame: 0-90 minutes post-operatively
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Apr 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 18811827Anderson BJ. Paracetamol (Acetaminophen): mechanisms of action. Paediatr Anaesth. 2008 Oct;18(10):915-21. doi: 10.1111/j.1460-9592.2008.02764.x.
- Background: PubMed 21627768Smith HS. Perioperative intravenous acetaminophen and NSAIDs. Pain Med. 2011 Jun;12(6):961-81. doi: 10.1111/j.1526-4637.2011.01141.x. Epub 2011 May 31.
- Background: PubMed 10443608Korpela R, Korvenoja P, Meretoja OA. Morphine-sparing effect of acetaminophen in pediatric day-case surgery. Anesthesiology. 1999 Aug;91(2):442-7. doi: 10.1097/00000542-199908000-00019.
- Background: PubMed 19583073Dashti GA, Amini S, Zanguee E. The prophylactic effect of rectal acetaminophen on postoperative pain and opioid requirements after adenotonsillectomy in children. Middle East J Anaesthesiol. 2009 Jun;20(2):245-9.
- Background: PubMed 20693884Hong JY, Kim WO, Koo BN, Cho JS, Suk EH, Kil HK. Fentanyl-sparing effect of acetaminophen as a mixture of fentanyl in intravenous parent-/nurse-controlled analgesia after pediatric ureteroneocystostomy. Anesthesiology. 2010 Sep;113(3):672-7. doi: 10.1097/ALN.0b013e3181e2c34b.
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.
Arlyne Thung, MD principal investigator
Nationwide Children's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Acetaminophen (paracetamol), Normal Saline Flush and Midazolam in people with Adenotonsillitis and Tonsillitis, run by Nationwide Children's Hospital 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 8 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 6 Apr 2017. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 6 Apr 2017). 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?
FLACC Pain Score Greater Than or Equal to 4 (time frame: 0-60 mins post-operatively). 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 NCT01691690, which also lists 5 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 6 Apr 2017.