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

Primary Purpose

Pain, Postoperative, Pain

Status
Recruiting
Phase
Phase 4
Locations
Canada
Study Type
Interventional
Intervention
Acetaminophen
Placebo
Sponsored by
McMaster Children's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pain, Postoperative focused on measuring acetaminophen, pain, neonate, infant, tylenol, paracetamol, postoperative, surgery

Eligibility Criteria

undefined - 12 Months (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Neonates, admitted to McMaster Children's Hospital NICU Has had major open, thoracic or abdominal surgery (see appendix 1, table 6). Informed consent obtained from guardian(s) Exclusion Criteria: Hepatic dysfunction AST, ALT or Bilirubin > 3x upper limit of normal INR ≥ 3.0 or PT greater than 20s regardless of vitamin K administration Renal dysfunction Increase in serum creatinine ≥ 2x baseline (baseline: lowest value in first 5 days of hospitalization) Urine output < 0.5 mL/kg/h for ≥ 12h Allergy or intolerance to acetaminophen or fentanyl Acetaminophen administration within 24 hours of the end of surgery Nerve blocks or epidurals Refusal or withdrawal of consent Enrolment in another competing trial No later than 12 hours after the end of surgery 12 months post gestational age or greater in age Birthweight greater or equal to 2,500g. Discharged from the McMaster NICU

Sites / Locations

  • McMaster Children's HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Comparator

Placebo

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Recruitment rate
Mean number of patients randomized per month
Follow up rate
Number of patients followed in completion from postoperative day 0 to 7
Medication compliance
Number of patients who received at least 80% of doses of study drugs at the correct dose and interval
Blinding index
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
Measured by the N-PASS Pain Scale as units on the scale (scale ranges from 0-10)
Daily fentanyl consumption
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
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
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
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
Length of time requiring intubation
Non-invasive ventilation
Length of time requiring CPAP, BiPAP, or supplemental oxygen
Enteral feeds
Time to first enteral feeds and time to full enteral feeds (using NICU's calculated goal feed)
Bowel movement
Time to first bowel movement
Glycerin suppository use
Number of patients requiring one or more glycerin suppositories
Length of stay
with discharge destination

Full Information

First Posted
December 6, 2022
Last Updated
April 24, 2023
Sponsor
McMaster Children's Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05678244
Brief Title
Intravenous Acetaminophen For Postoperative Pain in the Neonatal Intensive Care Unit
Acronym
IVA POP NICU
Official Title
Intravenous Acetaminophen For Postoperative Pain in the Neonatal Intensive Care Unit: A Feasibility Randomized Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 17, 2023 (Actual)
Primary Completion Date
August 2024 (Anticipated)
Study Completion Date
September 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
McMaster Children's Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pain, Postoperative, Pain
Keywords
acetaminophen, pain, neonate, infant, tylenol, paracetamol, postoperative, surgery

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Patients will be randomized to the control or comparator group. There will be 60 patients enrolled, with 30 patients per arm.
Masking
ParticipantCare ProviderInvestigatorOutcomes 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.
Allocation
Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Comparator
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Acetaminophen
Intervention Description
IV acetaminophen will be added to standard of care opioid based pain regimes.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
In control group placebo will be added to standard of care opioid based pain regimes.
Primary Outcome Measure Information:
Title
Recruitment rate
Description
Mean number of patients randomized per month
Time Frame
through study completion, an average of 1.5 years
Title
Follow up rate
Description
Number of patients followed in completion from postoperative day 0 to 7
Time Frame
90 days
Title
Medication compliance
Description
Number of patients who received at least 80% of doses of study drugs at the correct dose and interval
Time Frame
7 days
Title
Blinding index
Description
Responses of nurse's physician's, and research staff's guess of group assignment (control vs treatment) compared to actual group assignment
Time Frame
7 days
Secondary Outcome Measure Information:
Title
Postoperative Pain
Description
Measured by the N-PASS Pain Scale as units on the scale (scale ranges from 0-10)
Time Frame
every 6 hours for entire study period (7 days after surgery)
Title
Daily fentanyl consumption
Description
Fentanyl consumption will be recorded for each patient for each 24-hour period in the study period. Will be recorded in mcg/kg.
Time Frame
daily for 7 days
Title
Total fentanyl consumption
Description
Daily fentanyl consumption will be added together for the entire study period to determine the total amount of fentanyl consumed in mcg/kg.
Time Frame
7 days
Title
Daily Consumption of other analgesics
Description
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.
Time Frame
daily for 7 days
Title
Total consumption of other analgesics
Description
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.
Time Frame
7 days
Title
Invasive ventilation
Description
Length of time requiring intubation
Time Frame
90 days
Title
Non-invasive ventilation
Description
Length of time requiring CPAP, BiPAP, or supplemental oxygen
Time Frame
90 days
Title
Enteral feeds
Description
Time to first enteral feeds and time to full enteral feeds (using NICU's calculated goal feed)
Time Frame
90 days
Title
Bowel movement
Description
Time to first bowel movement
Time Frame
90 days
Title
Glycerin suppository use
Description
Number of patients requiring one or more glycerin suppositories
Time Frame
90 days
Title
Length of stay
Description
with discharge destination
Time Frame
90 days
Other Pre-specified Outcome Measures:
Title
Vomiting
Description
Number of patients with ≥ 1 episode of vomiting documented
Time Frame
7 days
Title
NG/Vygone
Description
Number of patients, mean duration
Time Frame
90 days
Title
Reintubation
Description
Number of patients
Time Frame
90 days
Title
Apnea
Description
Number of patients with oxygen saturation less than 94% or RR less than 20 breaths/min for more than 30 seconds
Time Frame
7 days
Title
Naloxone administration
Description
Number of patients
Time Frame
7 days
Title
Bradycardia
Description
Number of patients with HR less than 100 for more than 30 seconds
Time Frame
7 days
Title
Hypotension
Description
Number of patients with SBP less than 60, or requiring vasoactive medication
Time Frame
7 days
Title
Foley catheterization
Description
Number of patients, mean duration
Time Frame
7 days
Title
Feeding intolerance
Description
Number of patients: feeds stopped or decreased due to vomit/increased gastric output, or if diagnosed by the treating team
Time Frame
7 days
Title
Hepatic injury
Description
Number of patients with hepatic injury as defined in the protocol
Time Frame
90 days
Title
Mortality
Description
all cause mortality
Time Frame
90 days

10. Eligibility

Sex
All
Maximum Age & Unit of Time
12 Months
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Neonates, admitted to McMaster Children's Hospital NICU Has had major open, thoracic or abdominal surgery (see appendix 1, table 6). Informed consent obtained from guardian(s) Exclusion Criteria: Hepatic dysfunction AST, ALT or Bilirubin > 3x upper limit of normal INR ≥ 3.0 or PT greater than 20s regardless of vitamin K administration Renal dysfunction Increase in serum creatinine ≥ 2x baseline (baseline: lowest value in first 5 days of hospitalization) Urine output < 0.5 mL/kg/h for ≥ 12h Allergy or intolerance to acetaminophen or fentanyl Acetaminophen administration within 24 hours of the end of surgery Nerve blocks or epidurals Refusal or withdrawal of consent Enrolment in another competing trial No later than 12 hours after the end of surgery 12 months post gestational age or greater in age Birthweight greater or equal to 2,500g. Discharged from the McMaster NICU
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Victoria Archer, MD
Phone
506-721-9285
Email
vicki.archer@medportal.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mark Walton, MD
Organizational Affiliation
McMaster University
Official's Role
Principal Investigator
Facility Information:
Facility Name
McMaster Children's Hospital
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8N 3Z5
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Victoria Archer, MD
Phone
5067219285
Email
vicki.archer@medportal.ca

12. IPD Sharing Statement

Plan to Share IPD
No

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Intravenous Acetaminophen For Postoperative Pain in the Neonatal Intensive Care Unit

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