Postoperative Pain Control & Relief in Neonates

NCT03677830 | Terminated Phase 4 DMC FDA Drug

• 1 other identifier: 29544
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pain, Postoperative; Premature Infant; Opioid Use

Outcome Measures

Primary Outcomes (1)

• Total morphine exposure

  Total amount of morphine received by infants for pain control post-operatively in mg/kg

  72 hours following surgical procedure

Secondary Outcomes (1)

• Total "as needed" morphine exposure

  72 hours following surgical procedure

Other Outcomes (5)

• Apnea of >20 seconds

  72 hours following surgical procedure

• Time to first feed

  up to 2 weeks

• Time to full enteral feeds

  up to 8 weeks

Study Arms (2)

Intravenous Acetaminophen

ACTIVE COMPARATOR

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

Intravenous Placebo

PLACEBO COMPARATOR

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

Interventions

Acetaminophen DRUG

Scheduled intravenous acetaminophen for post-operative pain to minimize opiate exposure.

Also known as: Ofirmev 10 MG/ML Injectable Solution

Intravenous Acetaminophen

Saline DRUG

Intravenous saline will be administered at appropriate volume and schedule for control group as a placebo.

Intravenous Placebo

Eligibility Criteria

• Age: Up to 1 Month
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• St. Louis University: lead

Study Sites (1)

Cardinal Glennon Children's Hospital

St Louis, Missouri, 63104, United States

Location

MeSH Terms

Conditions

Pain, Postoperative; Premature Birth

Interventions

Acetaminophen; Sodium Chloride

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The intervention (intravenous acetaminophen) and placebo (saline) will be distributed by the pharmacy and are visually indistinguishable.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Pediatrics

Study Record Dates

• First Submitted: September 6, 2018
• First Posted: September 19, 2018
• Study Start: April 19, 2019
• Primary Completion: March 7, 2024
• Study Completion: March 7, 2024
• Last Updated: March 13, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)