The NEU-STIM Trial (NEU-STIM)

A Randomised Trial of Repetitive Versus Selective Tactile Stimulation for Preterm Infants at Birth: The NEU-STIM Trial

The aim of this study is to determine the effect of repetitive tactile stimulation compared to selective stimulation on oxygenation of the infant at 5 minutes after birth. Infants born before 32 weeks of gestation will be included in this trial. This is a stepped-wedge cluster randomised controlled trial. The participating centre, rather than the individual infant, will be the unit of randomisation. This design is appropriate to test the effect of an intervention that encompasses a behavioral aspect - in this case the performance of tactile stimulation.

Study Overview

• Status: Not yet recruiting
• Conditions: Infant, Premature, Diseases; Birth, Preterm
• Intervention / Treatment: Procedure: Selective tactile stimulation; Procedure: Repeated tactile stimulation

Detailed Description

Rationale: A randomised study demonstrated that preterm infants who received repetitive stimulation at birth (10 second episodes of stroking of the soles of the feet and/or back, followed by 10 seconds rest) showed an increase in respiratory effort. This may in turn improve clinical outcomes as improved breathing effort may reduce the need for invasive respiratory support. Tactile stimulation can be immediately and easily performed at birth at no extra cost. It therefore has great potential to be implemented in delivery rooms (DRs) worldwide.

Objective: To determine the effect of repetitive tactile stimulation compared to selective stimulation on oxygenation of the infant at 5 minutes after birth.

Study design: This is a stepped-wedge cluster randomised controlled trial. The participating centre, rather than the individual infant, will be the unit of randomisation. This design is appropriate to test the effect of an intervention that encompasses a behavioral aspect - in this case the performance of tactile stimulation.

Study population: Infants born before 32 weeks of gestation will be included in this trial.

Intervention: At the start of the study, each participating centre will perform selective tactile stimulation in accordance with international guidelines, as is their usual practice. Clinicians will gently rub the back, chest, extremities or soles of the feet if they consider the breathing of the infant to be insufficient or absent. In the second stage of the study, centres will be randomised to switch their stimulation approach to repetitive stimulation. Clinicians will then gently rub the back, chest, extremities or soles of the feet for 10 seconds. To avoid extinction of the stimulatory effect (reflex), every 10 second period of stimulation will be followed by 10 seconds of rest (no stimulation). Repetitive stimulation will be performed for the first 5 minutes of life, or longer if the breathing is still considered insufficient or absent.

Main study parameter: The proportion of infants with pre-ductal oxygen saturation (SpO2) ≥ 80%.

• Study Type: Interventional
• Enrollment (Estimated): 3280
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Janneke Dekker, PhD; Phone Number: +31715266620; Email: j.dekker@lumc.nl
• Study Contact Backup: Name: Colm O'Donnell, MD PhD; Phone Number: +35316373100; Email: codonnell@nmh.ie

Study Locations

• Austria
  • Graz, Austria, 8036
    • Medical University of Graz
    • Contact: Nariae Baik-Schneditz, MD PhD; Phone Number: +433163850
    • Principal Investigator: Nariae Baik-Schneditz, MD PhD
• Croatia
  • Rijeka, Croatia, 51000
    • Clinical Hospital Center Rijeka
    • Contact: Iva Bilic Cace, MD PhD; Phone Number: +38551658111
    • Principal Investigator: Iva Bilic Cace, MD PhD
• Ireland
  • Dublin, Ireland, D02 YH21
    • National Maternity Hospital
    • Contact: Colm O'Donnell, MD PhD; Phone Number: +35316373100; Email: codonnell@nmh.ie
    • Principal Investigator: Colm O'Donnell, MD PhD
• Netherlands
  • Zuid-Holland
    • Leiden, Zuid-Holland, Netherlands, 2333ZA
      • Leiden University Medical Center
      • Contact: Janneke Dekker, PhD; Phone Number: +31715266620; Email: j.dekker@lumc.nl
      • Principal Investigator: Janneke Dekker, PhD
• Spain
  • Valencia, Spain, 46026
    • La Fe University Hospital
    • Contact: Celia Barber Almenar; Phone Number: +34961244000
    • Principal Investigator: Celia Barber Almenar
    • Principal Investigator: Maximo Vento, MD PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Infants born before 32 weeks of gestation can be included in this trial after parental consent.

Exclusion Criteria:

• Infants will be excluded if they are found to have a congenital abnormality or condition that has an adverse effect on breathing/ventilation or oxygenation, including: congenital diaphragmatic hernia, trachea-oesophageal fistula, cyanotic heart disease and surfactant protein deficiency. Many of the infants enrolled in the study will later be diagnosed with respiratory distress syndrome (RDS); this will not render them ineligible for inclusion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Selective stimulation; At the start of the study, selective tactile stimulation will be performed at each participating centre in accordance with international guidelines. Clinicians will gently rub the back, chest, extremities or soles of the feet if they consider the breathing of the infant to be insufficient or absent. All other procedures in the delivery room and NICU will be performed according to international and local guidelines.	Procedure: Selective tactile stimulation; See arm
Experimental: Repeated stimulation; For each centre, a lot will be drawn which indicates the month in which the protocol for tactile stimulation changes from selective stimulation to repetitive stimulation. Repetitive stimulation is defined as gently rubbing the soles of the feet, back, chest, or extremities for 10 seconds. To prevent extinction of the stimulatory effect (reflex), every 10 second period of stimulation will be followed by 10 seconds rest (no stimulation). The repetitive stimulation will be performed for the first 5 minutes after birth, or longer if the breathing is still considered insufficient or absent. All other procedures in the delivery room and NICU will be performed according to international and local guidelines.	Procedure: Repeated tactile stimulation; See arm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SpO2>80	Proportion of infants with pre-ductal SpO2 >80%	At 5 minutes of life

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heart rate	Heart rate	At 5 minutes after birth
Number of infants who received CPAP <10min	Number of infants who received continuous positive airway pressure	Within 10 minutes after birth
Number of infants who received PPV <10min	Number of infants who received positive pressure ventilation	Within 10 minutes after birth
Number of infants who were intubated <10min	Number of infants who were endotracheally intubated	Within 10 minutes after birth
Number of infants who received chest compressions <10min		Within 10 minutes after birth
Number of infants who were administered adrenaline <10min	Adrenaline use	Within 10 minutes after birth
Number of infants who were administered volume expansion <10min		Within 10 minutes after birth
Max FiO2	Maximum FiO2	In the first 10 minutes after birth
Death <10min		Within 10 minutes after birth
Number of infants who were supported by CPAP in first week	CPAP use in the NICU	In the first week after birth
Number of infants who received surfactant in first week	Surfactant administration via INSURE, LISA or ET tube	In the first week after birth
Surfactant doses	Number of surfactant doses administered	In the first week after birth
Number of infants who were mechanically ventilated >12h	Mechanical ventilation for more than 12hours	In the first week after birth
Number of infants with abnormalities on the first cranial ultrasound	Abnormalities on first cranial ultrasound (IVH/PVL)	In first week after birth
Death	Mortality	In the first week after birth

Collaborators and Investigators

• Sponsor: Leiden University Medical Center
• Collaborators: European Society for Paediatric Research

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2024
• Primary Completion (Estimated): August 1, 2025
• Study Completion (Estimated): September 1, 2025

Study Registration Dates

• First Submitted: June 30, 2023
• First Submitted That Met QC Criteria: July 11, 2023
• First Posted (Actual): July 12, 2023

Study Record Updates

• Last Update Posted (Actual): July 12, 2023
• Last Update Submitted That Met QC Criteria: July 11, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Resuscitation; Preterm infant; Tactile stimulation
• Additional Relevant MeSH Terms: Infant, Newborn, Diseases; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Infant, Premature, Diseases; Premature Birth
• Other Study ID Numbers: N22.121

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No