A UK Interventional Trial in Premature Infants With Apnea of Prematurity Using a Simple, Non-invasive Vibratory Device to Study the Effectiveness in Supporting Breathing and General Stability

NCT04528030 | Unknown DMC

• 1 other identifier: CRR-WAVE-122-CIP
• Study Type: interventional
• Target: 17
• Locations: 0 countries
• Sites: N/A

Brief Summary

Purpose of Study: Apnoea of Prematurity (AOP) is common, affecting the majority of infants born \<34 weeks gestational age (GA). Apnea is accompanied by intermittent hypoxia (IH), which contributes to multiple pathologies, including retinopathy of prematurity (ROP), sympathetic ganglia injury, impaired pancreatic islet cell and bone development, and neurodevelopmental disabilities. Standard of care for AOP/IH includes prone positioning, positive pressure ventilation, and caffeine therapy. The objective of this device is to provide an adjunct to current AoP treatment to support breathing in premature infants by using a simple, non-invasive vibratory device placed over limb proprioceptor fibers, an intervention using the principle that limb movements facilitate breathing. Methods Used: Premature infants (27+6 - 34+6 weeks GA) with clinical confirmed weeks with diagnosis of Apnoea of Prematurity. Caffeine therapy was not a reason for exclusion. Small vibration devices were placed on one hand and one foot and activated in a 6 hour ON/OFF sequence for a total of 24 hours. Heart rate, respiratory rate, oxygen saturation (SpO2), and breathing pauses were continuously collected.

Conditions

Apnea of Newborn; Hypoxia Neonatal; Bradycardia Neonatal

Keywords

cardio-respiratory stability; neonate; premature infant; proprioceptive stimulation; Apnoea of Prematurity; Medical Device

Outcome Measures

Primary Outcomes (1)

• Compare the cumulative burden of AoP with or without WAVE stimulation

  The primary objective is to compare the cumulative duration of breathing pauses related to Apnoea of Prematurity (AoP) between periods of presence and absence of tactile vibratory device stimulation as adjunct to standard care.

  24 hours

Secondary Outcomes (8)

• Compare the number of AoP events.

  24 hours

• Compare the number of desaturations (SpO2<86%) events

  24 hours

• Compare the cumulative depth of desaturations.

  24 hours

• Compare the cumulative duration of desaturations (SpO2<86%) events.

  24 hours

• Compare the number of bradycardia events.

  24 hours

Other Outcomes (1)

• Post trial feedback

  up to 24 weeks

Study Arms (2)

Treatment starting with an on ON cycle

OTHER

The treatment will start ON cycle for 6 hours, followed by OFF cycle for 6 hours, followed by OFF cycle for 6 hours and finished with ON cycle for 6 hours.

Device: WAVE device

Treatment starting with an on OFF cycle

OTHER

The treatment will start OFF cycle for 6 hours, followed by ON cycle for 6 hours, followed by OFF cycle for 6 hours and finished with ON cycle for 6 hours.

Device: WAVE device

Interventions

WAVE device DEVICE

WAVE applies a transcutaneous vibration to the soles of the foot and palms of the hand to elicit nerve signalling from pressure and other limb proprioceptor sensors to pontine, cerebellar, and medullary brain areas that coordinate limb movement and reflexively activate brain areas controlling breathing. The WAVE device is a battery-operated product to reduce the episodes of Apnoea of Prematurity by vibratory stimulation to the hand and foot.

Also known as: limb proprioceptive stimulation, kinesthetic stimulation

Treatment starting with an on OFF cycle; Treatment starting with an on ON cycle

Eligibility Criteria

• Age: 28 Weeks - 35 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Written informed consent
• Gestational age \> 27+6weeks, \< 34+1 weeks
• Diagnosis of apnoea of prematurity (AOP) on clinical observations (atleast 4 AoP episodes and atleast one ABD event (equal and less 85% SpO2)- define clearly).
• During screening baby must demonstrate \>4 AoP/1 ABD events
• Minimum 48 hours after extubation.

You may not qualify if:

• Inotropes
• Infants with major congenital anomalies/malformations which will influence central nervous system and long-term outcomes in these infants, such as cardiac anomalies (except for Patent Ductus Arteriosus or Ventricular Septal Defect) or major neurological malformations, like meningoencephalocele, holoprosencephaly
• Neonates who have apnoea from airway issues like laryngomalacia or tracheomalacia.
• Neonates with a history of hypoxic-ischemic encephalopathy or Grade IV intraventricular haemorrhage
• Infants that are currently intubated and invasive ventilation
• Congenital skin malformations, skin conditions due to recurrent illness (microcirculation concerns).
• Patients being treated for sepsis.

Sponsors & Collaborators

• Inspiration Healthcare: lead
• Brighton and Sussex University Hospitals NHS Trust: collaborator

Related Publications (17)

• Kesavan K, Frank P, Cordero DM, Benharash P, Harper RM. Neuromodulation of Limb Proprioceptive Afferents Decreases Apnea of Prematurity and Accompanying Intermittent Hypoxia and Bradycardia. PLoS One. 2016 Jun 15;11(6):e0157349. doi: 10.1371/journal.pone.0157349. eCollection 2016.

  PMID: 27304988 BACKGROUND

• Martin RJ, Di Fiore JM, Macfarlane PM, Wilson CG. Physiologic basis for intermittent hypoxic episodes in preterm infants. Adv Exp Med Biol. 2012;758:351-8. doi: 10.1007/978-94-007-4584-1_47.

  PMID: 23080182 BACKGROUND

• te Pas AB, Davis PG, Kamlin CO, Dawson J, O'Donnell CP, Morley CJ. Spontaneous breathing patterns of very preterm infants treated with continuous positive airway pressure at birth. Pediatr Res. 2008 Sep;64(3):281-5. doi: 10.1203/PDR.0b013e31817d9c35.

  PMID: 18458652 BACKGROUND

• Robertson CM, Watt MJ, Dinu IA. Outcomes for the extremely premature infant: what is new? And where are we going? Pediatr Neurol. 2009 Mar;40(3):189-96. doi: 10.1016/j.pediatrneurol.2008.09.017.

  PMID: 19218032 BACKGROUND

• Henderson-Smart DJ, Steer PA. Caffeine versus theophylline for apnea in preterm infants. Cochrane Database Syst Rev. 2010 Jan 20;2010(1):CD000273. doi: 10.1002/14651858.CD000273.pub2.

  PMID: 20091506 BACKGROUND

• Sweet DG, Carnielli V, Greisen G, Hallman M, Ozek E, Te Pas A, Plavka R, Roehr CC, Saugstad OD, Simeoni U, Speer CP, Vento M, Visser GHA, Halliday HL. European Consensus Guidelines on the Management of Respiratory Distress Syndrome - 2019 Update. Neonatology. 2019;115(4):432-450. doi: 10.1159/000499361. Epub 2019 Apr 11.

  PMID: 30974433 BACKGROUND

• Hummel P, Puchalski M, Creech SD, Weiss MG. Clinical reliability and validity of the N-PASS: neonatal pain, agitation and sedation scale with prolonged pain. J Perinatol. 2008 Jan;28(1):55-60. doi: 10.1038/sj.jp.7211861. Epub 2007 Oct 25.

  PMID: 18165830 BACKGROUND

• Randerath W, Verbraecken J, Andreas S, Arzt M, Bloch KE, Brack T, Buyse B, De Backer W, Eckert DJ, Grote L, Hagmeyer L, Hedner J, Jennum P, La Rovere MT, Miltz C, McNicholas WT, Montserrat J, Naughton M, Pepin JL, Pevernagie D, Sanner B, Testelmans D, Tonia T, Vrijsen B, Wijkstra P, Levy P. Definition, discrimination, diagnosis and treatment of central breathing disturbances during sleep. Eur Respir J. 2017 Jan 18;49(1):1600959. doi: 10.1183/13993003.00959-2016. Print 2017 Jan.

  PMID: 27920092 BACKGROUND

• Shevtsova NA, Marchenko V, Bezdudnaya T. Modulation of Respiratory System by Limb Muscle Afferents in Intact and Injured Spinal Cord. Front Neurosci. 2019 Mar 26;13:289. doi: 10.3389/fnins.2019.00289. eCollection 2019.

  PMID: 30971888 BACKGROUND

• Potts JT, Rybak IA, Paton JF. Respiratory rhythm entrainment by somatic afferent stimulation. J Neurosci. 2005 Feb 23;25(8):1965-78. doi: 10.1523/JNEUROSCI.3881-04.2005.

  PMID: 15728836 BACKGROUND

• Dekker J, Martherus T, Cramer SJE, van Zanten HA, Hooper SB, Te Pas AB. Tactile Stimulation to Stimulate Spontaneous Breathing during Stabilization of Preterm Infants at Birth: A Retrospective Analysis. Front Pediatr. 2017 Apr 3;5:61. doi: 10.3389/fped.2017.00061. eCollection 2017.

  PMID: 28421171 BACKGROUND

• Solkoff N, Matuszak D. Tactile stimulation and behavioral development among low-birthweight infants. Child Psychiatry Hum Dev. 1975 Fall;6(1):33-7. doi: 10.1007/BF01434430.

  PMID: 1238237 BACKGROUND

• Lovell JR, Eisenfeld L, Rosow E, Adam J, Lapin C, Bronzino JD. Vibrotactile stimulation for treatment of neonatal apnea: a preliminary study. Conn Med. 1999 Jun;63(6):323-5. No abstract available.

  PMID: 10432764 BACKGROUND

• Pichardo R, Adam JS, Rosow E, Bronzino J, Eisenfeld L. Vibrotactile stimulation system to treat apnea of prematurity. Biomed Instrum Technol. 2003 Jan-Feb;37(1):34-40. doi: 10.2345/0899-8205(2003)37[34:VSSTTA]2.0.CO;2.

  PMID: 12613292 BACKGROUND

• Pietravalle A, Cavallin F, Opocher A, Madella S, Cavicchiolo ME, Pizzol D, Putoto G, Trevisanuto D. Neonatal tactile stimulation at birth in a low-resource setting. BMC Pediatr. 2018 Sep 20;18(1):306. doi: 10.1186/s12887-018-1279-4.

  PMID: 30236090 BACKGROUND

• Frank UA, Bordiuk JM, Borromeo-McGrail V, Saltzman MB, Keitel HG. Treatment of apnea in neonates with an automated monitor-actuated apnea arrestor. Pediatrics. 1973 May;51(5):878-83. No abstract available.

  PMID: 4703399 BACKGROUND

• Cramer SJE, Dekker J, Dankelman J, Pauws SC, Hooper SB, Te Pas AB. Effect of Tactile Stimulation on Termination and Prevention of Apnea of Prematurity: A Systematic Review. Front Pediatr. 2018 Mar 2;6:45. doi: 10.3389/fped.2018.00045. eCollection 2018.

  PMID: 29552548 BACKGROUND

Related Links

• Sponsor website

MeSH Terms

Conditions

Asphyxia Neonatorum; Premature Birth; Apnea

Condition Hierarchy (Ancestors)

Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Oana Dr Anton, MBBS MRCPCH

  Brighton and Sussex University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jacqueline van Druten, BScMedHons

CONTACT

07407614698; jacqueline.vandruten@inspiration-healthcare.com

R, A

CONTACT

CRR-WAVE@inspiration-healthcare.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The investigator analyzing the 4 cycles will not know whether it's an ON of OFF cycle during the 24 hour treatment period.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Sequential Assignment In the same subject there were 2 periods: OFF cycles (6 hours x 2): 'No intervention' period (no vibrations) - two 6 hour epochs - total of 12 hours of 'No intervention' ON cycles (6hours x 2). Experimental period (with vibrations) - two 6 hour epochs - total of 12 hours of 'vibration intervention' In the same subjects cardio-respiratory parameters will be continuously monitored through the 24 hour treatment period of 4 cycles- heart rate, respiratory rate and oxygen saturation were compared during the experimental period (vibration) and during the no intervention period (no vibration).

Study Record Dates

• First Submitted: August 20, 2020
• First Posted: August 27, 2020
• Study Start: April 1, 2021
• Primary Completion: December 31, 2021
• Study Completion: April 1, 2022
• Last Updated: February 18, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will share