Intravenous Acetaminophen For Postoperative Pain in the Neonatal Intensive Care Unit

NCT ID: NCT05678244

Last Updated: 2023-04-25

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-04-17
• Study Completion Date: 2024-09-30

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.

Conditions

Pain, Postoperative; Pain

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Acetaminophen

Intervention Type: DRUG

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

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Interventions

Acetaminophen

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

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

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

• Maximum Eligible Age: 12 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

McMaster Children's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Victoria Archer

Resident Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mark Walton, MD

Role: PRINCIPAL_INVESTIGATOR

McMaster University

Locations

McMaster Children's Hospital

Hamilton, Ontario, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Victoria Archer, MD

Role: CONTACT

vicki.archer@medportal.ca

506-721-9285

Facility Contacts

Victoria Archer, MD

Role: primary

vicki.archer@medportal.ca

5067219285

References

Archer VA, Samiee-Zafarghandy S, Farrokyhar F, Briatico D, Braga LH, Walton JM. Intravenous acetaminophen for postoperative pain in the neonatal intensive care unit: A protocol for a pilot randomized controlled trial (IVA POP). PLoS One. 2023 Nov 20;18(11):e0294519. doi: 10.1371/journal.pone.0294519. eCollection 2023.

Reference Type: DERIVED

PMID: 37983228 (View on PubMed)

Other Identifiers

14887-GRA

Identifier Type: -

Identifier Source: org_study_id