Postoperative Pain Control & Relief in Neonates (POPCORN)

Pain control for newborns has made significant improvements over the last 30 years. The use of narcotics remains the standard of care for neonates undergoing minor and major surgeries. Narcotics, however, are associated with adverse effects such as respiratory depression, prolonged intubation and withdrawal symptoms. Acetaminophen (Tylenol©) has been proposed as an adjunct to reduce narcotic use but current evidence from well designed studies in newborns and premature infants is limited. This study will randomly assign neonates undergoing a surgery to either morphine plus acetaminophen or morphine alone for pain control. The subjects will be followed for 72 hours after the operation and evaluate the benefits of acetaminophen for pain control.

Study Overview

• Status: Terminated
• Conditions: Pain, Postoperative; Opioid Use; Premature Infant
• Intervention / Treatment: Drug: Acetaminophen; Drug: Saline

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63104
      • Cardinal Glennon Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 1 month (Child)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• All neonates ≥ 28 weeks of gestation and <44 weeks of gestation undergoing general surgery procedures (below) and managed postoperatively in the Neonatal Intensive Care Unit (NICU).

Minor procedures Inguinal hernia repair Laparoscopic or open gastrostomy tube placement Peritoneal drain placement for spontaneous intestinal perforation Gastroschisis bedside patch closure

Major procedures Laparoscopic or open Nissen fundoplication, duodenal atresia repair, Hirschsprung pull through, Ladd's procedure or excision of abdominal cyst Thoracoscopy or thoracotomy procedure Enterostomy or colostomy creation Exploratory laparotomy Revision or closure of enterostomy or colostomy Any Gastroschisis or omphalocele repair in operating room Repair or staged repair of congenital anorectal malformations Resection of sacrococcygeal teratoma

Exclusion Criteria:

• Any infant admitted with preoperative diagnosis of neonatal abstinence syndrome (NAS) or known intrauterine opiate exposure
• Any diagnosis of hepatitis exclusive of TPN-related biliary cholestasis
• Renal disease with creatinine >2.0 mg/dl at enrollment
• Intraventricular hemorrhage grade 3 or greater, or cerebellar hemorrhage
• Any patient with myotonic dystrophy or other congenital disease limiting validity of pain scoring
• Opiate exposure within 14 days of operative procedure
• Non-English-speaking parents/guardians

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Intravenous Acetaminophen; Infants randomized to the intervention arm will receive scheduled IV acetaminophen per LexiComp dosing guideline (28 0/7-32 6/7 weeks 10 mg/kg/dose every 12 hours; 33 0/7-38 6/7 weeks 10 mg/kg/dose every 8 hours; >39 0/7 weeks 10 mg/kg/dose every 6 hours). N-PASS scores will guide administration of IV morphine. Continuous infusion of morphine will be started if an infant requires 3 doses of morphine within a 6-hour period and titrated as needed per N-PASS scores.	Drug: Acetaminophen; Scheduled intravenous acetaminophen for post-operative pain to minimize opiate exposure.; Other Names: Ofirmev 10 MG/ML Injectable Solution
Placebo Comparator: Intravenous Placebo; Infants randomized to the control arm will receive normal saline placebo IV at the appropriate volume and times for the gestational age. IV acetaminophen is concentrated at 10 mg/ml; corresponding saline volumes will be 1 ml to 5 ml, approximately, based on subject weight. Control infants will also have N-PASS scores assessed using the same protocol following the surgical procedure for 72 hours. Dosing of IV morphine will be the same as the dosing for the intervention arm.	Drug: Saline; Intravenous saline will be administered at appropriate volume and schedule for control group as a placebo.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total morphine exposure	Total amount of morphine received by infants for pain control post-operatively in mg/kg	72 hours following surgical procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total "as needed" morphine exposure	Total "as needed" or prn doses of morphine received by infants for pain control post-operatively in mg/kg	72 hours following surgical procedure

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Apnea of >20 seconds	Apnea episodes of >20 seconds documented by nursing staff after surgical procedure	72 hours following surgical procedure
Time to first feed	Number of hours to first enteral feeding after surgical procedure	up to 2 weeks
Time to full enteral feeds	Number of hours/days until receiving all nutritional support enterally following surgical procedure	up to 8 weeks
Time to endotracheal extubation	Number of hours from surgical procedure to endotracheal extubation	up to 2 weeks
Incidence of opiate withdrawal symptoms	Number of infants that develop withdrawal symptoms from opiate exposure	up to 8 weeks

Collaborators and Investigators

• Sponsor: St. Louis University

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2019
• Primary Completion (Actual): March 7, 2024
• Study Completion (Actual): March 7, 2024

Study Registration Dates

• First Submitted: September 6, 2018
• First Submitted That Met QC Criteria: September 17, 2018
• First Posted (Actual): September 19, 2018

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 11, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antipyretics; Acetaminophen
• Other Study ID Numbers: 29544

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.: No