IVA POP NICU: Intravenous Acetaminophen For Postoperative Pain in the Neonatal Intensive Care Unit

Sponsor

McMaster Children's Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05678244

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

3.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The goal of this pilot randomized clinical trial is to determine the effect of the addition of IV acetaminophen to opioid-based pain regimes for infants admitted to the neonatal intensive care unit (NICU) after surgery.

This is a pilot trial; the main goals are to make sure our study methods work before performing a larger study.

The main clinical aims are:

Determine if adding IV acetaminophen reduces pain
Determine if adding IV acetaminophen reduces opioid use
Determine if adding IV acetaminophen reduces complications

Participants will be randomized to two groups:

Comparator: Fentanyl and IV acetaminophen Control: Fentanyl and placebo

Patients will receive either IV acetaminophen or placebo at regular intervals for seven days after surgery. Patients will be followed daily during that period. Charts will be reviewed at 90-days for final outcomes.

Condition or Disease	Intervention/Treatment	Phase
Pain, Postoperative Pain	Drug: Acetaminophen Drug: Placebo	Phase 4

Detailed Description

Purpose: Opioid use in neonates is associated with short and long-term adverse events. Multi-modal pain control offers the ability to control pain while reducing opioid exposure. This topic has been relatively unexamined in preterm and term neonates. Specifically, this trial aims to evaluate the effect of adding IV acetaminophen to standard opioid-based pain regimes in neonates in the neonatal intensive care unit (NICU) undergoing major abdominal and thoracic surgery.

Objectives: The primary aim of the proposed study is to determine the feasibility and cost of conducting a multicenter, randomized control trial to compare the efficacy of IV acetaminophen and fentanyl, to fentanyl and saline placebo, in terms of reduction of postoperative pain, opioid use, adverse events. The primary outcome is feasibility; secondarily, efficacy and safety will be assessed.

Design: This single-center, parallel-arm, placebo-controlled, fully blinded, randomized controlled external feasibility trial will enroll patients admitted in the neonatal intensive care unit (NICU) who have undergone major, thoracic, or abdominal surgery. Patients will be randomized 1:1, with parallel allocation to receive acetaminophen and fentanyl or fentanyl and saline placebo. All study staff, clinical staff and guardians will be blinded. As this is a pilot study, no sample size will be calculated, however; we aim to enroll 60 patients. A sample size calculation will be completed for the full RCT if it is deemed feasible from the results of this study. Patients will be followed for the day of surgery and the following 7 postoperative days (192 hours) and have their charts reviewed at 90 days.

Impact: The results of this study will be used to determine the feasibility of conducting a multi-center RCT to assess the effect of IV acetaminophen on fentanyl infusions in postoperative neonatal patients. The effect of IV acetaminophen for postoperative pain in preterm neonates has yet to be studied, this trial would generate novel insights into its efficacy. The prolonged follow-up period would also provide novel insights into recovery throughout the entire perioperative period.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Patients will be randomized to the control or comparator group. There will be 60 patients enrolled, with 30 patients per arm.Patients will be randomized to the control or comparator group. There will be 60 patients enrolled, with 30 patients per arm.

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

IV acetaminophen and saline appear identical in solution. They will be administered at identical rates. Care providers, participants' parents, investigators, outcomes assessors, and statisticians will remain blinded.

Primary Purpose:

Treatment

Official Title:

Intravenous Acetaminophen For Postoperative Pain in the Neonatal Intensive Care Unit: A Feasibility Randomized Controlled Trial

Anticipated Study Start Date :

Feb 1, 2023

Anticipated Primary Completion Date :

Aug 1, 2024

Anticipated Study Completion Date :

Sep 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Comparator Standard of care + IV acetaminophen: Baseline fentanyl infusion, with dosage escalations, deescalations, and additional boluses and analgesics (excluding oral or rectal acetaminophen) determined by the patient's physician (this represents standard of care at this institution) with the addition of IV acetaminophen every 4 or 6 hours at weight-appropriate doses based on the patient's gestational age.	Drug: Acetaminophen IV acetaminophen will be added to standard of care opioid based pain regimes.
Placebo Comparator: Placebo Standard of care + placebo: Baseline fentanyl infusion, with dosage escalations, deescalations, and additional boluses and analgesics (excluding oral or rectal acetaminophen) determined by the patient's physician (this represents standard of care at this institution) with the addition of an IV saline placebo every 4 or 6 hours at a rate which would mimic their dose of acetaminophen.	Drug: Placebo In control group placebo will be added to standard of care opioid based pain regimes.

Arm

Intervention/Treatment

Active Comparator: Comparator

Standard of care + IV acetaminophen: Baseline fentanyl infusion, with dosage escalations, deescalations, and additional boluses and analgesics (excluding oral or rectal acetaminophen) determined by the patient's physician (this represents standard of care at this institution) with the addition of IV acetaminophen every 4 or 6 hours at weight-appropriate doses based on the patient's gestational age.

Drug: Acetaminophen

IV acetaminophen will be added to standard of care opioid based pain regimes.

Placebo Comparator: Placebo

Standard of care + placebo: Baseline fentanyl infusion, with dosage escalations, deescalations, and additional boluses and analgesics (excluding oral or rectal acetaminophen) determined by the patient's physician (this represents standard of care at this institution) with the addition of an IV saline placebo every 4 or 6 hours at a rate which would mimic their dose of acetaminophen.

Drug: Placebo

In control group placebo will be added to standard of care opioid based pain regimes.

Outcome Measures

Primary Outcome Measures

Recruitment rate [through study completion, an average of 1.5 years]
Mean number of patients randomized per month
Follow up rate [90 days]
Number of patients followed in completion from postoperative day 0 to 7
Medication compliance [7 days]
Number of patients who received at least 80% of doses of study drugs at the correct dose and interval
Blinding index [7 days]
Responses of nurse's physician's, and research staff's guess of group assignment (control vs treatment) compared to actual group assignment

Secondary Outcome Measures

Postoperative Pain [every 6 hours for entire study period (7 days after surgery)]
Measured by the Comfort-NEO Scale as units on the scale (scale ranges from 6-30).
Daily fentanyl consumption [daily for 7 days]
Fentanyl consumption will be recorded for each patient for each 24-hour period in the study period. Will be recorded in mcg/kg.
Total fentanyl consumption [7 days]
Daily fentanyl consumption will be added together for the entire study period to determine the total amount of fentanyl consumed in mcg/kg.
Daily Consumption of other analgesics [daily for 7 days]
Consumption of other analgesics will be recorded for each patient for each 24-hour period in the study period. Will be recorded in mg or mcg /kg.
Total consumption of other analgesics [7 days]
Daily consumption of other analgesics will be added together for the entire study period to determine the total amount of fentanyl consumed in mg or mcg/kg.
Invasive ventilation [90 days]
Length of time requiring intubation
Non-invasive ventilation [90 days]
Length of time requiring CPAP, BiPAP, or supplemental oxygen
Enteral feeds [90 days]
Time to first enteral feeds and time to full enteral feeds (using NICU's calculated goal feed)
Bowel movement [90 days]
Time to first bowel movement
Glycerin suppository use [90 days]
Number of patients requiring one or more glycerin suppositories
Length of stay [90 days]
with discharge destination

Other Outcome Measures

Vomiting [7 days]
Number of patients with ≥ 1 episode of vomiting documented
NG/Vygone [90 days]
Number of patients, mean duration
Reintubation [90 days]
Number of patients
Apnea [7 days]
Number of patients with oxygen saturation less than 94% or RR less than 20 breaths/min for more than 30 seconds
Naloxone administration [7 days]
Number of patients
Bradycardia [7 days]
Number of patients with HR less than 100 for more than 30 seconds
Hypotension [7 days]
Number of patients with SBP less than 60, or requiring vasoactive medication
Foley catheterization [7 days]
Number of patients, mean duration
Feeding intolerance [7 days]
Number of patients: feeds stopped or decreased due to vomit/increased gastric output, or if diagnosed by the treating team
Hepatic injury [90 days]
Number of patients with hepatic injury as defined in the protocol
Mortality [90 days]
all cause mortality