A study to compare two different ways of giving fentanyl drug– continuous infusion or intermittent doses for pain relief in newborn babies

Phase 3

Recruiting

• Conditions: Analgesia and Sedation for neonates on mechanical ventilation

• Registration Number: CTRI/2014/11/005190
• Lead Sponsor: Institutional Review Board

Brief Summary

Background

Fentanyl is commonly used for analgesia in newborn infants. The drug has a rapid clearance in adults. But hepatic metabolism is immature at birth, thus the half- life is prolonged in neonates. So, intermittent doses of fentanyl may be as good as continuous infusion in maintaining serum concentrations and hence the analgesic efficacy in neonates.

Aim

To compare continuous infusion and intermittent doses of fentanyl for analgesia in neonates using serum concentrations, pain scores and side-effects

Methods

In the present study, newborn babies who are likely to need mechanical ventilation and hence analgesia and sedation for preferably 48 hours (minimum of 24 hours) will be recruited into the study after informed written consent. The babies will be stratified into 2 categories of <32 weeks or ≥32 weeks gestational age. In both groups, babies will be administered a loading dose of fentanyl (1 microgram/kg/dose) at the time of intubation, or at the time of starting ventilator care if the baby has already been intubated in the labour room or casualty.

Babies will be randomized into two groups: continuous infusion of fentanyl (Group 1) or intermittent doses once in every 4 hours (Group 2). The babies in the continuous group and intermittent group will be compared based on: 1) serum fentanyl concentrations 2) clinical efficacy 3) adverse effects.

Serum concentrations of fentanyl will be estimated as follows:

Group 1 - Continuous infusion - samples (0.5 ml) will be collected

a. Prior to starting continuous infusion(0 hour) and at 2,8 and 24 hours from start of infusion

b. At 36 and 48 hours - 2 samples on Day 2

Group 2 - Intermittent doses–

a. Peak (Cmax) and trough concentrations of the 1st dose (at 0 and 4 hours)

b. Peak and trough concentrations of the 6th dose (at 20 and 24 hours) on day 1

c. On Day 2 , peak and trough of the 12th dose or the last dose, whichever is later

Pain assessment will be done clinically using standard neonatal pain scoring systems, viz. N-PASS to assess ongoing pain, and NIPS to assess acute pain during heel prick, intravenous cannulation or other procedures.

Adverse effects of fentanyl will also be assessed in both groups

1. Decreased gastrointestinal motility will be assessed daily based on not passing meconium, and gastric retention defined by the volume of nasogastric aspirate/vomiting in 24 hours.

2. Urinary retention (loss of spontaneous urination with enlarged bladder/ need for catheterization) will be evaluated daily.

3. Incidence of hypotension (Blood pressure < 10th percentile for the gestational age and postnatal age)

4. Chest wall rigidity (clinically defined as no chest rise despite patent airway and adequate pressures with either mechanical or manual ventilation).

Detailed Description

Not available

Study Timeline

• Study Start: 2014-01-11
• Last Update Posted: 2014-06-11

Recruitment & Eligibility

• Status: Open to Recruitment
• Sex: All
• Target Recruitment: 98

Inclusion Criteria

Newborn babies who are likely to require mechanical ventilation for 48 hours (minimum 24 hours).

Exclusion Criteria

1.Major congenital anomalies/ chromosomal disorders 2.Hypoxic Ischemic encephalopathy (HIE) stage 2 or 3 3.Postoperative babies 4.Refusal of consent.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To compare the exposure as concentrations of Fentanyl achieved in the serum between the two groups	Continuous Infusion - Fentanyl serum concentrations at: 0, 2, 8, 24 hours on DAY 1. 36 and 48 hours on DAY 2. | Intermittent dosage Group - Fentanyl serum concentrations as peak and trough concentrations for dose 1 and 6–DAY 1, peak and trough for dose 12 (or last dose, whichever is later) on DAY 2

Secondary Outcome Measures

Name	Time	Method
To measure the exposure as Cmax (peak concentration) and area under concentration time curve (AUC 0-24 hours or AUC 0-48 hours) in babies receiving continuous infusion of fentanyl	Fentanyl serum concentrations at 0, 2, 8, 24 hours on DAY 1 and 36, 48 hours on DAY 2
To measure the exposure as Cmax (when measured) at each bolus and AUC, through the 24 hour (or 48 hour) period, using limited time points, in babies receiving intermittent bolus doses of fentanyl	Fentanyl serum concentrations as peak and trough concentrations for dose 1 and 6 on DAY 1, peak and trough for dose 12 (or last dose, whichever is later) on DAY 2
To find the inter-individual variability in serum concentrations of fentanyl in the two groups, especially the effect of gestational age on fentanyl clearance	Day 1 and 2 of fentanyl
To compare the analgesic efficacy between continuous infusion and intermittent bolus doses of fentanyl using pain scores	Day 1 and 2 of fentanyl
To compare the side effects of fentanyl between the two groups	Day 1 and 2 of fentanyl

Trial Locations

Locations (1)

Level 3 nursery; 🇮🇳 Vellore, TAMIL NADU, India

Level 3 nursery

🇮🇳Vellore, TAMIL NADU, India

Dr Abiramalatha T

Principal investigator

04163073311

abi_paeds@yahoo.com