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Intravenous Acetaminophen For Postoperative Pain in the Neonatal Intensive Care Unit

Phase 4
Recruiting
Conditions
Pain, Postoperative
Pain
Interventions
Drug: Placebo
Registration Number
NCT05678244
Lead Sponsor
McMaster Children's Hospital
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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
60
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboStandard 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.
ComparatorAcetaminophenStandard 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.
Primary Outcome Measures
NameTimeMethod
Follow up rate90 days

Number of patients followed in completion from postoperative day 0 to 7

Medication compliance7 days

Number of patients who received at least 80% of doses of study drugs at the correct dose and interval

Recruitment ratethrough study completion, an average of 1.5 years

Mean number of patients randomized per month

Blinding index7 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
NameTimeMethod
Enteral feeds90 days

Time to first enteral feeds and time to full enteral feeds (using NICU's calculated goal feed)

Glycerin suppository use90 days

Number of patients requiring one or more glycerin suppositories

Daily fentanyl consumptiondaily 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 consumption7 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 analgesicsdaily 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.

Invasive ventilation90 days

Length of time requiring intubation

Bowel movement90 days

Time to first bowel movement

Postoperative Painevery 6 hours for entire study period (7 days after surgery)

Measured by the N-PASS Pain Scale as units on the scale (scale ranges from 0-10)

Length of stay90 days

with discharge destination

Total consumption of other analgesics7 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.

Non-invasive ventilation90 days

Length of time requiring CPAP, BiPAP, or supplemental oxygen

Trial Locations

Locations (1)

McMaster Children's Hospital

🇨🇦

Hamilton, Ontario, Canada

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