Postoperative PainNCT01140724
Personalizing Perioperative Analgesia in Children
An observational study of Postoperative Pain, run by Senthil Sadhasivam at 1 site in United States.
Trial summary
In the United States alone, each year approximately 5 million children undergo painful surgery, many of them experience serious side-effects with opioids and inadequate pain relief. Read more about this study
- Who is it for?
- Ages 3 to 15 years
- Conditions the study is for
- Postoperative Pain
- How many people
- 1,200 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Feb 2022to 25 Dec 2027
- Phase
- Observational
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 3 to 15 years
- All sexes
- No healthy volunteers
- Child
Study population: Children, 3-15 years of age, undergoing tonsillectomy or adenotonsillectomy at the Riley Hospital for Children, who have consented to participate in an observational clinical study as approved by the IU IRB, protocol # 1707325115.
Who may be able to join
- boys and girls,
- 3-15 years of age,
- all races,
- American Society of Anesthesiologists (ASA) physical status 1,2, and 3,
- children with history of significant snoring suggestive of obstructive sleep apnea (OSA),
- Scheduled for tonsillectomy (T) or tonsillectomy and adenoidectomy (T and A).
Who cannot join
- allergic to study medications
- developmental delay,
- liver and renal diseases,
- preoperative pain requiring analgesics,
- children who have problems with pupil or pupillary reaction due to disease
- preoperative medications influencing pupillary size
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- non-English speaking participants and families
- Body Mass Index ≥30
- Participants undergoing additional procedures during surgery
- Children with certain cardiac conditions
- Children with severe lung disease
- Children with a history of seizures currently treated on medication
- Children with psychiatric/psychological conditions for which patient currently takes medication
Trial locations and contacts
1 site in 1 country.
United States1 site
UPMC Children's Hospital
Pittsburgh, Pennsylvania, 15224
About this study
Official title: Predicting Perioperative Opioid Adverse Effects and Personalizing Analgesia in Children
In the United States alone, each year approximately 5 million children undergo painful surgery, many of them experience serious side-effects with opioids and inadequate pain relief. Safe and effective analgesia is an important unmet critical medical need in children and its continued existence is an important perioperative safety and economic problem. Inadequate pain relief and serious side effects from perioperative opioids occur frequently in up to 50% of children. Morphine, the most commonly used perioperative opioid, has a narrow therapeutic index and large inter-patient variations in analgesic response and serious side effects. Frequent inter-individual variations in responses to morphine have significant clinical and economic impact with inadequate pain relief at one end of the spectrum of responses and serious adverse effects such as respiratory depression at the other end. Much of the inter-individual variability in response to a dose of morphine following surgical procedures can be explained by single nucleotide polymorphisms (SNPs) in a subset of the genes that encode proteins involved in pain mechanisms and opioid pathway.
Read the detailed description
Measures and Procedures: Participants will receive standard care, standard anesthetic and an intraoperative dose of morphine per the clinical team.
Research procedures will include:
- Blood draws for genotyping candidate genes and exploratory genes
- Standardized PACU (post anesthesia care unit) Protocol: Subjective pain assessments: Numerical Rating Scale (NRS) 0 to 10. Objective assessment with FLACC (facial expression; leg movement; activity; cry; and consolability) scale, 0-10.
- Significant postoperative pain will be managed in the PACU with rescue doses of morphine and opioids by the clinical team. Analgesic interventions and morphine requirements are collected
- Effects of opioids on pupil measures
- Respiratory response to 5% carbon dioxide preoperatively and postoperatively (first 350 patients only). Another measure of end tidal carbon dioxide will be implemented when the device is clinically available.
- Serial blood draws for morphine pharmacokinetic modeling (through subject #351).
- Opioid adverse effects in PACU and at home.
- Conditions
- Postoperative Pain
- Keywords
- pain, genes, morphine, respiratory depression, tonsillectomy, children, Opioid adverse effects, Pharmacogenetics of morphine, Pharmacokinetics of morphine, Personalizing analgesia
- Medical subject headings
- Pain, Postoperative, Pain, Respiratory Insufficiency
What is being measured
The primary outcome is the main question the study is designed to answer.
Look at polymorphisms in genes that regulate pain perception, opioid transport and opioid receptor signaling to see if there is a higher susceptibility to pain and morphine requirement.
Look at polymorphisms in genes that regulate pain perception, opioid transport and opioid receptor signaling to see if there is a relationship to more pain and need for a higher morphine requirement.
Measured: After tonsillectomy surgery (duration of post anesthesia care unit stay)
Secondary outcomes (1)
Evaluate relationship of pupil reaction and response to 5% carbon dioxide to adverse effects of morphine
Measured: After tonsillectomy surgery (duration of post anesthesia care unit stay)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2010 (estimated)
- Study start7 Feb 2022
- Primary completion16 Aug 2027 (estimated)
- Study completion25 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Postoperative PainStudies 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
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 1,200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Senthil Sadhasivam
- Sponsor type
- University, hospital or other
- Collaborators
- Children's Hospital Medical Center, Cincinnati, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Sponsor-investigator, Senthil Sadhasivam, University of Pittsburgh
- Investigators
- Senthilkumar Sadhasivam, MD, MPH, Principal investigator, University of Pittsburgh, UPMC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01140724
- Sponsor's protocol ID
- STUDY21070173
- Other IDs
- R01HD089458
- Status last verified
- Jun 2026
- First submitted
- 8 Jun 2010
- Last updated
- 17 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Packiasabapathy S, Zhang X, Ding L, Aruldhas BW, Pawale D, Sadhasivam S. Quantitative Pupillometry as a Predictor of Pediatric Postoperative Opioid-Induced Respiratory Depression. Anesth Analg. 2021 Oct 1;133(4):991-999. doi: 10.1213/ANE.0000000000005579.
PubMed 34029273Hahn D, Fukuda T, Euteneuer JC, Mizuno T, Vinks AA, Sadhasivam S, Emoto C. Influence of MRP3 Genetics and Hepatic Expression Ontogeny for Morphine Disposition in Neonatal and Pediatric Patients. J Clin Pharmacol. 2020 Aug;60(8):992-998. doi: 10.1002/jcph.1592. Epub 2020 Feb 24.
PubMed 32090339Chidambaran V, Venkatasubramanian R, Zhang X, Martin LJ, Niu J, Mizuno T, Fukuda T, Meller J, Vinks AA, Sadhasivam S. ABCC3 genetic variants are associated with postoperative morphine-induced respiratory depression and morphine pharmacokinetics in children. Pharmacogenomics J. 2017 Mar;17(2):162-169. doi: 10.1038/tpj.2015.98. Epub 2016 Jan 26.
PubMed 26810133Sadhasivam S, Zhang X, Chidambaran V, Mavi J, Pilipenko V, Mersha TB, Meller J, Kaufman KM, Martin LJ, McAuliffe J. Novel associations between FAAH genetic variants and postoperative central opioid-related adverse effects. Pharmacogenomics J. 2015 Oct;15(5):436-42. doi: 10.1038/tpj.2014.79. Epub 2015 Jan 6.
PubMed 25558980Sadhasivam S, Chidambaran V, Olbrecht VA, Costandi A, Clay S, Prows CA, Zhang X, Martin LJ. Opioid-related adverse effects in children undergoing surgery: unequal burden on younger girls with higher doses of opioids. Pain Med. 2015 May;16(5):985-97. doi: 10.1111/pme.12660. Epub 2014 Dec 17.
PubMed 25521773Sadhasivam S, Chidambaran V, Olbrecht VA, Esslinger HR, Zhang K, Zhang X, Martin LJ. Genetics of pain perception, COMT and postoperative pain management in children. Pharmacogenomics. 2014 Feb;15(3):277-84. doi: 10.2217/pgs.13.248.
PubMed 24533707Prows CA, Zhang X, Huth MM, Zhang K, Saldana SN, Daraiseh NM, Esslinger HR, Freeman E, Greinwald JH, Martin LJ, Sadhasivam S. Codeine-related adverse drug reactions in children following tonsillectomy: a prospective study. Laryngoscope. 2014 May;124(5):1242-50. doi: 10.1002/lary.24455. Epub 2013 Nov 13.
PubMed 24122716Sadhasivam S, Krekels EH, Chidambaran V, Esslinger HR, Ngamprasertwong P, Zhang K, Fukuda T, Vinks AA. Morphine clearance in children: does race or genetics matter? J Opioid Manag. 2012 Jul-Aug;8(4):217-26. doi: 10.5055/jom.2012.0119.
PubMed 22941849Sadhasivam S, Chidambaran V, Ngamprasertwong P, Esslinger HR, Prows C, Zhang X, Martin LJ, McAuliffe J. Race and unequal burden of perioperative pain and opioid related adverse effects in children. Pediatrics. 2012 May;129(5):832-8. doi: 10.1542/peds.2011-2607. Epub 2012 Apr 23.
PubMed 22529273