Intravenous Acetaminophen For Postoperative Pain in the Neonatal Intensive Care Unit

Pain Clinical Trial

— IVA POP NICU  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05678244
• Other study ID #: 14887-GRA
• Status: Recruiting
• Phase: Phase 4
• Start date: April 17, 2023
• Est. completion date: September 2024

Study information

• Verified date: April 2023
• Source: McMaster Children's Hospital
• Contact: Victoria Archer, MD
• Phone: 506-721-9285
• Email: vicki.archer[@]medportal.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: September 2024
• Est. primary completion date: August 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 12 Months

Eligibility

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

Related Conditions & MeSH terms

• Pain
• Pain, Postoperative

Intervention

Drug:
• Acetaminophen
IV acetaminophen will be added to standard of care opioid based pain regimes.
• Placebo
In control group placebo will be added to standard of care opioid based pain regimes.

Locations

Country	Name	City	State
Canada	McMaster Children's Hospital	Hamilton	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
McMaster Children's Hospital

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Vomiting	Number of patients with = 1 episode of vomiting documented	7 days
Other	NG/Vygone	Number of patients, mean duration	90 days
Other	Reintubation	Number of patients	90 days
Other	Apnea	Number of patients with oxygen saturation less than 94% or RR less than 20 breaths/min for more than 30 seconds	7 days
Other	Naloxone administration	Number of patients	7 days
Other	Bradycardia	Number of patients with HR less than 100 for more than 30 seconds	7 days
Other	Hypotension	Number of patients with SBP less than 60, or requiring vasoactive medication	7 days
Other	Foley catheterization	Number of patients, mean duration	7 days
Other	Feeding intolerance	Number of patients: feeds stopped or decreased due to vomit/increased gastric output, or if diagnosed by the treating team	7 days
Other	Hepatic injury	Number of patients with hepatic injury as defined in the protocol	90 days
Other	Mortality	all cause mortality	90 days
Primary	Recruitment rate	Mean number of patients randomized per month	through study completion, an average of 1.5 years
Primary	Follow up rate	Number of patients followed in completion from postoperative day 0 to 7	90 days
Primary	Medication compliance	Number of patients who received at least 80% of doses of study drugs at the correct dose and interval	7 days
Primary	Blinding index	Responses of nurse's physician's, and research staff's guess of group assignment (control vs treatment) compared to actual group assignment	7 days
Secondary	Postoperative Pain	Measured by the N-PASS Pain Scale as units on the scale (scale ranges from 0-10)	every 6 hours for entire study period (7 days after surgery)
Secondary	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.	daily for 7 days
Secondary	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.	7 days
Secondary	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.	daily for 7 days
Secondary	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.	7 days
Secondary	Invasive ventilation	Length of time requiring intubation	90 days
Secondary	Non-invasive ventilation	Length of time requiring CPAP, BiPAP, or supplemental oxygen	90 days
Secondary	Enteral feeds	Time to first enteral feeds and time to full enteral feeds (using NICU's calculated goal feed)	90 days
Secondary	Bowel movement	Time to first bowel movement	90 days
Secondary	Glycerin suppository use	Number of patients requiring one or more glycerin suppositories	90 days
Secondary	Length of stay	with discharge destination	90 days