Clinical trial NCT05678244: Intravenous Acetaminophen For Postoperative Pain in the Neonatal Intensive Care Unit
Official title: Intravenous Acetaminophen For Postoperative Pain in the Neonatal Intensive Care Unit: A Feasibility Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Pain, Postoperative
Pain
Keywords: acetaminophen
pain
neonate
infant
tylenol
paracetamol
postoperative
surgery
Lead sponsor: McMaster Children's Hospital
Sponsor class: OTHER
First posted: 2023-01-10
Enrollment: 60
Sex: ALL
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients will be randomized to the control or comparator group. There will be 60 patients enrolled, with 30 patients per arm.
Primary purpose: TREATMENT

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:

1. Determine if adding IV acetaminophen reduces pain
2. Determine if adding IV acetaminophen reduces opioid use
3. 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.

Eligibility criteria: Inclusion Criteria:

1. Neonates, admitted to McMaster Children's Hospital NICU
2. Has had major open, thoracic or abdominal surgery (see appendix 1, table 6).
3. Informed consent obtained from guardian(s)

Exclusion Criteria:

1. Hepatic dysfunction

   * AST, ALT or Bilirubin \> 3x upper limit of normal
   * INR ≥ 3.0 or PT greater than 20s regardless of vitamin K administration
2. 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
3. Allergy or intolerance to acetaminophen or fentanyl
4. Acetaminophen administration within 24 hours of the end of surgery
5. Nerve blocks or epidurals
6. Refusal or withdrawal of consent
7. Enrolment in another competing trial
8. No later than 12 hours after the end of surgery
9. 12 months post gestational age or greater in age
10. Birthweight greater or equal to 2,500g.
11. Discharged from the McMaster NICU

Primary outcomes:
measure: Recruitment rate
timeFrame: through study completion, an average of 1.5 years
measure: Follow up rate
timeFrame: 90 days
measure: Medication compliance
timeFrame: 7 days
measure: Blinding index
timeFrame: 7 days
Secondary outcomes:
measure: Postoperative Pain
timeFrame: every 6 hours for entire study period (7 days after surgery)
measure: Daily fentanyl consumption
timeFrame: daily for 7 days
measure: Total fentanyl consumption
timeFrame: 7 days
measure: Daily Consumption of other analgesics
timeFrame: daily for 7 days
measure: Total consumption of other analgesics
timeFrame: 7 days
measure: Invasive ventilation
timeFrame: 90 days
measure: Non-invasive ventilation
timeFrame: 90 days
measure: Enteral feeds
timeFrame: 90 days
measure: Bowel movement
timeFrame: 90 days
measure: Glycerin suppository use
timeFrame: 90 days
measure: Length of stay
timeFrame: 90 days
Other outcomes:
measure: Vomiting
timeFrame: 7 days
measure: NG/Vygone
timeFrame: 90 days
measure: Reintubation
timeFrame: 90 days
measure: Apnea
timeFrame: 7 days
measure: Naloxone administration
timeFrame: 7 days
measure: Bradycardia
timeFrame: 7 days
measure: Hypotension
timeFrame: 7 days
measure: Foley catheterization
timeFrame: 7 days
measure: Feeding intolerance
timeFrame: 7 days
measure: Hepatic injury
timeFrame: 90 days
measure: Mortality
timeFrame: 90 days
Locations:
city: Hamilton
country: Canada
facility: McMaster Children's Hospital
state: Ontario
Study officials:
affiliation: McMaster University
name: Mark Walton, MD
role: PRINCIPAL_INVESTIGATOR
References: