NeoFent-I Study; Fentanyl Treatment in Newborn Infants; a Pharmacokinetic, Pharmacodynamic and Pharmacogenetic Study

NeoFent-I Study; Fentanyl Treatment in Newborn Infants; a Pharmacokinetic, Pharmacodynamic and Pharmacogenetic Study. Prestudy to NeoOpioid; No Pain During Infancy by Adapting Off-patent Medicines. EU FP7:HEALTH - 2007-4.2-1

The study will assess the efficacy of fentanyl using a pharmacokinetic/pharmacodynamic (PK/PD) model where the concentration of the drug is related to effect curve (pain score change in response to standardized procedural pain). Further cortical, physiological and biochemical responses to fentanyl will be assessed, elucidating the feasibility before the main study project (NeoOpioid) start.

Study Overview

• Status: Completed
• Conditions: Pain
• Intervention / Treatment: Drug: Fentanyl (5 microgram/ml) prediluted ampoules

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 4

Contacts and Locations

Study Locations

• Sweden
  • Lund, Sweden, 221 85
    • Neonatal Intensive Care Unit, Skåne University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 4 weeks (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Clinical indication for analgesia before any of following procedures;

  1. insertion of peripheral IV-catheter
  2. insertion of arterial cannula
  3. insertion of chest tube
  4. other skin breaking procedure.
• Possibility to obtain blood samle after the procedure (indwelling line)
• Infants all gestational ages.
• Postnatal age 0-28 days
• Informed written parental concent

Exclusion Criteria:

• Concurrent or previous opioid administration (72 h interval required)
• Abdominal surgery
• Major chromosomal anomaly
• Neonatal encephalopathy
• Use of muscle relaxant
• Hypothermia treatment after hypoxic-ischemic insult
• Clinical or biochemical evidence of hepatic failure
• Participation in other intervention trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fentanyl for procedural pain; A dose of Fentanyl 5 microgram/ml, 0.5 microgram/kg (anticipated medium pain) or 2 microgram/kg (anticipated strong pain) will be given prior to a painful procedure during NICU-care. Repeated doses or complementary analgesics will be administered according to pain assessment and clinical judgement. This is not an RCT with several arms.	Drug: Fentanyl (5 microgram/ml) prediluted ampoules; Bolus; Fentanyl (5 microgram/ml) 0,5 microgram/kg (0.1 ml/kg) is administered over 1 min starting 3-5 min before the lighter skin breaking procedure. Fentanyl (5 microgram/ml) 2 microgram/kg is administered over 10 min before the start of the more painful procedur ( pleura drainage or tracheal intubation).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics; fentanyl clearance	Serum concentration will be analysed and the clearance will be calculated with NONMEM pharmacokinetics.	48 hours
Pharmacokinetics; fentanyl clearance	The serum concentration values will be analysed as Area under the curve, AUC	6 hours
Pharmacodynamics; Amplitude integrated electroencephalography (aEEG)	Background activity	6 hours
Pharmacodynamics; Amplitude integrated electroencephalography (aEEG),	Seizure activity	6 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacodynamics, change in vital parameters	Change in heart rate	6 hours
Pharmacodynamics, change in vital parameters	Change in mean arterial blood pressure	6 hours
Pharmacodynamics, change in vital parameters	Change in near infrared spectroscopy	6 hours
Pharmacodynamics, behavioural response	Pain assessment with the Premature Infant Pain Profile-revised (PIPP) score for procedural pain (0-21, with the highest value if strong pain in extremely preterm infants)	6 hours
Pharmacodynamics, hormonal response	Blood levels of cortisol	48 hours

Collaborators and Investigators

• Sponsor: Lund University
• Collaborators: Karolinska Institutet
• Investigators: Principal Investigator: Vineta Fellman, Professor, Dep. of Pediatrics, Lund University, Sweden

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2012
• Primary Completion (Actual): December 31, 2014
• Study Completion (Actual): December 31, 2014

Study Registration Dates

• First Submitted: February 13, 2019
• First Submitted That Met QC Criteria: March 29, 2019
• First Posted (Actual): April 1, 2019

Study Record Updates

• Last Update Posted (Actual): April 1, 2019
• Last Update Submitted That Met QC Criteria: March 29, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: pharmacogenetics; pain assessment; analgesia; neonates; procedural pain; physiological response
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Opioid; Narcotics; Adjuvants, Anesthesia; Fentanyl
• Other Study ID Numbers: EU-Grant 223767; 2011-000310-19 (EudraCT Number)