The T REX Pilot Study: a Study to Investigate the Use of an Alternative Anaesthetic in Infants.

An Open Label Pilot Study of Feasibility of a Dexmedetomidine-Remifentanil-Caudal Anaesthetic for Infant Lower Abdominal/Lower Extremity Surgery: The TREX Pilot Study

Animal studies suggest general anaesthetics harm the developing brain. It is unclear if these findings are relevant to humans but the issue has become a major concern. Recent data have found that monkeys exposed to anaesthesia as infants grow up to have slower learning than those not exposed.

The aim of the TREX pilot study is to determine the feasibility of an alternative anaesthetic regimen for lower abdominal/lower extremity surgery in infants 1-12 months of age.

Study Overview

• Status: Completed
• Conditions: Surgical Procedures, Operative
• Intervention / Treatment: Drug: Dexmedetomidine; Drug: Remifentanil; Drug: Bupivacaine; Drug: Ropivacaine

Detailed Description

Animal studies suggest general anaesthetics harm the developing brain. It is unclear if these findings are relevant to humans but the issue has become a major concern. Recent data have found that monkeys exposed to anaesthesia as infants grow up to have slower learning than those not exposed.

The aim of the TREX pilot study is to determine the feasibility of an alternative anaesthetic regimen for lower abdominal/lower extremity surgery in infants 1-12 months of age.

An alternative anaesthetic regimen comprises a dexmedetomidine-based anaesthetic, augmented with an opioid (remifentanil) and a regional nerve block (such as a caudal).

This open label prospective single arm pilot study will enrol 60 infants aged 1-12 months scheduled for lower limb, urologic, or lower abdominal surgery. After sevoflurane induction, the infants will have a caudal anaesthetic and intravenous dexmedetomidine and remifentanil.

The outcome will be need for intervention for light anaesthesia, intervention for haemodynamic changes and rate of abandoning the protocol. Recovery times will also be recorded.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Parkville, Victoria, Australia, 3052
      • Royal Children's Hospital
• Singapore
  • Singapore, Singapore, 229899
    • KK Women's and Children's Hospital
• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Texas
    • Dallas, Texas, United States, 75390
      • The University of Texas Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 1 year (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Infants aged 1 to 12 months (corrected age)
• ASA I or II
• Infants undergoing lower abdominal/lower extremity surgery anticipated to be > 120 minutes in duration
• Surgery requires caudal regional nerve block

Exclusion Criteria:

• ASA III or higher
• Any contraindication to caudal analgesia
• Any contraindication to an inhalational induction with sevoflurane
• Allergies to any medication in study protocol
• Planned admission to an ICU postoperatively (except level II or III neonatal ICU)
• Planned tracheal intubation postoperatively
• Mechanical ventilation postoperatively

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: Active open label single arm; Dexmedetomidine- remifentanil- caudal based anaesthetic for lower abdominal/lower extremity surgery. Dexmedetomidine (Precedex): loading dose: 1 mcg/kg over 10 minutes. Infusion: Start 1 mcg/kg/hr; titrate up or down within 50% of starting doses as needed Remifentanil (Ultiva): loading dose: 1 mcg/kg over 1-2 minutes. Infusion: Start at 0.2 mcg/kg/min. Titrate up or down (max 0.5 mcg/kg/min) as needed Caudal- Bupivacaine (Marcaine) 0.175%-0.25% or Ropivacaine (Naropin) 0.2% with dose at discretion of anaesthetist

Drug: Dexmedetomidine; Loading dose:1 mcg/kg over 10 minutes. Infusion: Start 1-1.5 mcg/kg/hr. Titrate up or down within 50% of starting doses as needed.; Other Names: Precedex; Drug: Remifentanil; Loading dose: 1 mcg/kg over 1-2 minutes. Infusion: Start at 0.2-0.5 mcg/kg/min. Titrate up or down (max 0.5 mcg/kg/min) as needed.; Other Names: Ultiva; Drug: Bupivacaine; Administered in caudal/epidural/field block: 0.175%-0.25% (dose at discretion of anaesthetist); Other Names: Marcaine; Drug: Ropivacaine; Administered in caudal/epidural/field block: 0.2% (dose at discretion of anaesthetist); Other Names: Naropin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants who need for intervention for light anaesthesia	Rescue treatment for light anaesthesia will be given if hypertension MAP > 80 mmHg (confirmed with repeated measure) and/or patient movement.	120 minutes (duration of surgery)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants who need for intervention for haemodynamic changes	Rescue treatment for mild Hypotension will be given if MAP is between 40 mmHg and <50 mmHg (confirmed with repeated measure); Moderate Hypotension will be defined as MAP <40 mmHg; Mild bradycardia will be defined as HR <100 bpm for over one minute; Significant bradycardia will be defined as <70 bpm over one minute	120 minutes (duration of surgery)
Time to recovery after anaesthesia		Time from last dressing to: eye opening, removal of airway device, first feed, and a modified Aldrete Score of 9-10 (average 30 minutes-4 hours)
Number of participants who have respiratory complications	Any episode of coughing, oxygen desaturation <90%, breath holding > 15 seconds	Start of anaesthesia until discharge from PACU (average 1-4 hours)
Number of participants who have pain after anaesthesia	FLACC (Face, Legs, Activity, Cry, Consolability) scale. The scale is scored in a range of 0-10 with 0 representing no pain.	End of surgery until discharge from PACU ( average 1-4 hours)
Number of participants who require rescue analgesia in PACU	Analgesia: morphine 0.025-0.05 mg/kg IV for analgesia; repeat 20 minutes. Analgesia thereafter as per local protocol	End of surgery until discharge from PACU (average 1-4 hours)

Collaborators and Investigators

• Sponsor: Murdoch Childrens Research Institute
• Collaborators: Baylor College of Medicine; Children's Hospital of Philadelphia; University Hospital, Geneva; Boston Children's Hospital; The Cleveland Clinic; UMC Utrecht; Oregon Health and Science University; University of Texas Southwestern Medical Center; Children's Hospital Medical Center, Cincinnati; KK Women's and Children's Hospital; Sydney Children's Hospitals Network; The Royal Children's Hospital Melbourne; Princess Margaret Hospital for Children; Starship Children's Health; Gaslini Children's Hospital
• Investigators: Principal Investigator: Andrew J Davidson, MD, Murdoch Childrens Research Institute

Study record dates

Study Major Dates

• Study Start: May 1, 2015
• Primary Completion (Actual): September 1, 2016
• Study Completion (Actual): September 1, 2016

Study Registration Dates

• First Submitted: January 26, 2015
• First Submitted That Met QC Criteria: January 28, 2015
• First Posted (Estimate): February 2, 2015

Study Record Updates

• Last Update Posted (Estimate): October 26, 2016
• Last Update Submitted That Met QC Criteria: October 24, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: lower extremity; abdominal
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Analgesics, Opioid; Narcotics; Hypnotics and Sedatives; Anesthetics, Local; Remifentanil; Dexmedetomidine; Bupivacaine; Ropivacaine
• Other Study ID Numbers: 35014

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Data will be presented as group data and no individual will be identified.