Hydromorphone vs Fentanyl in Children Undergoing Tonsillectomy Surgery

A Randomized Controlled Trial to Compare Hydromorphone vs Fentanyl in Children Undergoing Tonsillectomy Surgery

A RCT to compare hydromorphone versus fentanyl for pain control following tonsillectomy or adenotonsillectomy surgery.

Study Overview

• Status: Completed
• Conditions: Obstructive Sleep Apnea; Tonsillitis
• Intervention / Treatment: Drug: Fentanyl; Drug: Hydromorphone

Detailed Description

This is a randomized clinical trial with masked assessment, comparing recovery indices for patients receiving intermediate acting versus short acting opioid analgesia using hydromorphone or fentanyl as intraoperative analgesics. An otherwise standardized anesthetic and analgesic regimen will be utilized, consistent with routine care at SLCH. Patients will be randomized 1:1 in block sizes of 5 per group. Patients will be randomized to receive either hydromorphone or fentanyl throughout the perioperative period by opening a sealed protocol envelope.

• Study Type: Interventional
• Enrollment (Actual): 189
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Alan Hifko, MD; Phone Number: 314-273-3943; Email: ahifko@wustl.edu

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine/Barnes-Jewish Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 15 years (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Children ages 2 to 15 years old
2. Presenting for tonsillectomy or adenotonsillectomy surgery
3. American Society of Anesthesiologists Physical Status (ASAPS) Classification 1, 2 or 3
4. Provide Informed Consent / Assent (as appropriate)

Exclusion Criteria:

1. Additional Concurrent surgeries, exclusive of myringotomy tubes, minor oral/nasal procedures (e.g. frenulectomy), and endoscopic procedures
2. Revision tonsillectomy or revision adenotonsillectomy surgery
3. Known pregnancy
4. Any condition which would make the participant, in the opinion of the investigator or the attending anesthesiologist caring for the patient, unsuitable for the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Hydromorphone	Drug: Hydromorphone; Patients will be randomized to one of two opioids for the treatment of post-operative pain.
Active Comparator: Fentanyl	Drug: Fentanyl; Fentanyl

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Amount of rescue opioid medications administered - hydromorphone group	Postoperative opioid medication expressed in morphine equivalents	up to 48 hours post surgery
Amount of rescue opioid medications administered - fentanyl group	Postoperative opioid medication expressed in morphine equivalents	up to 48 hours post surgery
Evaluation of participant's pain - hydromorphone group	Revised Face, Legs, Activity, Cry, Consolability (rFLACC) Scale Each of the five categories (F) Face; (L) Legs; (A) Activity; (C) Cry; (C) Consolability is scored from 0-2, which results in a total score between zero and ten. 0=no pain/relaxed, 10=distressed/in pain	up to 48 hours post surgery
Evaluation of participant's pain - fentanyl group	Revised Face, Legs, Activity, Cry, Consolability (rFLACC) Scale Each of the five categories (F) Face; (L) Legs; (A) Activity; (C) Cry; (C) Consolability is scored from 0-2, which results in a total score between zero and ten. 0=no pain/relaxed, 10=distressed/in pain	up to 48 hours post surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Preoperative Amsterdam Preoperative Anxiety Scale - hydromorphone group	Caregiver of the participant is asked questions regarding the child's anxiety level prior to surgery. The questions asked: 1) I am worried about the anesthetic, 2) The anesthetic is on my mind continually, 3) I would like to know as much as possible about the anesthetic, 4) I am worried about the procedure, 5) The procedure is on my mind continually, 6) I would like to know as much as possible about the procedure The measure of agreement with these statements should be graded on a 5-point Likert scale from 1 "not at all" to 5 "extremely." A score of ≥11 identify anxious patients in clinical practice.	up to 12 hours prior to surgery
Preoperative Amsterdam Preoperative Anxiety Scale - fentanyl group	Caregiver of the participant is asked questions regarding the child's anxiety level prior to surgery. The questions asked: 1) I am worried about the anesthetic, 2) The anesthetic is on my mind continually, 3) I would like to know as much as possible about the anesthetic, 4) I am worried about the procedure, 5) The procedure is on my mind continually, 6) I would like to know as much as possible about the procedure The measure of agreement with these statements should be graded on a 5-point Likert scale from 1 "not at all" to 5 "extremely." A score of ≥11 identify anxious patients in clinical practice.	up to 12 hours prior to surgery
Yale Preoperative Anxiety Scale - hydromorphone group	Assessing child anxiety during the induction of anesthesia. It contains 22 items in 5 categories: activity, emotional expressivity, state of arousal, vocalization, and use of parents. Each category receives a score on a scale of 0 to 4 (6 for vocalization) according to the behavior of the patient, with 0 = no anxiety and 4 (or 6 for vocalization) = high anxiety.	up to 12 hours prior to surgery
Yale Preoperative Anxiety Scale - fentanyl group	Assessing child anxiety during the induction of anesthesia. It contains 22 items in 5 categories: activity, emotional expressivity, state of arousal, vocalization, and use of parents. Each category receives a score on a scale of 0 to 4 (6 for vocalization) according to the behavior of the patient, with 0 = no anxiety and 4 (or 6 for vocalization) = high anxiety.	up to 12 hours prior to surgery
ASA physical status classification score from preoperative assessment - hydromorphone group	ASA I A normal healthy patient ASA II A patient with mild systemic disease ASA III A patient with severe systemic disease ASA IV A patient with severe systemic disease that is a constant threat to life ASA V A moribund patient who is not expected to survive without the operation ASA VI A declared brain-dead patient whose organs are being removed for donor purposes	up to 12 hours prior to surgery
ASA physical status classification score from preoperative assessment - fentanyl group	ASA I A normal healthy patient ASA II A patient with mild systemic disease ASA III A patient with severe systemic disease ASA IV A patient with severe systemic disease that is a constant threat to life ASA V A moribund patient who is not expected to survive without the operation ASA VI A declared brain-dead patient whose organs are being removed for donor purposes	up to 12 hours prior to surgery
Optional opioid plasma concentrations - hydromorphone group	Blood collection at three time points using mass spectroscopy (This is optional for participants)	up to 48 hours after surgery
Optional opioid plasma concentrations - fentanyl group	Blood collection at three time points using mass spectroscopy (This is optional for participants)	up to 48 hours after surgery
Adverse events - hydromorphone group	Nausea/vomiting, witnessed apneic events, desaturation events, respiratory depression, re-intubation, decreased oxygen saturation	up to 48 hours after surgery
Adverse events - fentanyl group	Nausea/vomiting, witnessed apneic events, desaturation events, respiratory depression, re-intubation, decreased oxygen saturation	up to 48 hours after surgery
NIH PROMIS - hydromorphone group	Patient satisfaction, behavior and pain scores over past 7 days. Scale of 1 - 6, with 1=had no pain and 6=almost always	up to 48 hours after surgery
NIH PROMIS - fentanyl group	Patient satisfaction, behavior and pain scores over past 7 days. Scale of 1 - 6, with 1=had no pain and 6=almost always	up to 48 hours after surgery
NIH PROMIS - hydromorphone group	Patient caregiver satisfaction, behavior and pain scores over past 7 days. Scale of 1 - 6, with 1=had no pain and 6=almost always	up to 48 hours after surgery
NIH PROMIS - fentanyl group	Patient caregiver satisfaction, behavior and pain scores over past 7 days. Scale of 1 - 6, with 1=had no pain and 6=almost always	up to 48 hours after surgery
Child Hospital Survey (CAHPS) - hydromorphone group	Patient caregiver satisfaction. Scale of 1 - 4 with 1=never and 6=always	up to 48 hours after surgery
Child Hospital Survey (CAHPS) - fentanyl group	Patient caregiver satisfaction. Scale of 1 - 4 with 1=never and 6=always	up to 48 hours after surgery

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Investigators: Principal Investigator: Michael Montana, MD PhD, Washington University School of Medicine

Publications and helpful links

General Publications

• Bhattacharyya N, Lin HW. Changes and consistencies in the epidemiology of pediatric adenotonsillar surgery, 1996-2006. Otolaryngol Head Neck Surg. 2010 Nov;143(5):680-4. doi: 10.1016/j.otohns.2010.06.918.
• Friedman NR, Perkins JN, McNair B, Mitchell RB. Current practice patterns for sleep-disordered breathing in children. Laryngoscope. 2013 Apr;123(4):1055-8. doi: 10.1002/lary.23709. Epub 2013 Feb 4.
• Brown KA. Outcome, risk, and error and the child with obstructive sleep apnea. Paediatr Anaesth. 2011 Jul;21(7):771-80. doi: 10.1111/j.1460-9592.2011.03597.x. Epub 2011 May 3.

Study record dates

Study Major Dates

• Study Start (Actual): February 26, 2020
• Primary Completion (Actual): April 1, 2022
• Study Completion (Actual): April 1, 2022

Study Registration Dates

• First Submitted: December 27, 2019
• First Submitted That Met QC Criteria: January 14, 2020
• First Posted (Actual): January 18, 2020

Study Record Updates

• Last Update Posted (Actual): March 2, 2023
• Last Update Submitted That Met QC Criteria: March 1, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Apnea; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Sleep Apnea Syndromes; Pharyngitis; Sleep Apnea, Obstructive; Tonsillitis; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Opioid; Narcotics; Adjuvants, Anesthesia; Fentanyl; Hydromorphone
• Other Study ID Numbers: 201912042

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes