Dexmedetomidine for LISA Procedure in Preterm Infants

RDS Clinical Trial

— DEXLISA  

Official title:

Dexmedetomidine for LISA Procedure in Preterm Infants: a Pilot Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04820101
• Other study ID #: DEXLISA 920/CE Marca
• Status: Not yet recruiting
• Phase: N/A
• Start date: May 15, 2021
• Est. completion date: April 1, 2023

Study information

• Verified date: April 2021
• Source: University of Padova
• Contact: Paola Lago, MD
• Phone: 00390422322608
• Email: paola.lago[@]aulss2.veneto.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The investigators aim to evaluate: the effectiveness of dexmedetomidine for analgesia and sedation during LISA procedure, without compromising the respiratory drive; the safety of this drug on the preterm infant in a pilot study.

Description:

Information will be given to parents of preterm babies <36 wGA upon their admission to the NICU (neonatal intensive care unit), and informed consent will be obtained as soon as possible. Eligible babies for LISA procedure (dyspneic and FiO2 > 0.30 on CPAP pressure of at least 6 cmH2O) undergo sedation with dexmedetomidine 1 mcg/kg, administered slowly iv in 10 minutes, together with non pharmacological techniques. After the step of sedation LISA is performed. Before/during and after the procedure pain will be assessed by the NIPS scale and the quality of intubation will be evaluated; then other events related to the procedure will be strictly collected for the first 24 hours. Babies will then be managed in usual NICU way and clinical data will be unregistered on respiratory, neurological and hemodynamic outcomes during the hospital stay, and especially at discharge.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: April 1, 2023
• Est. primary completion date: April 1, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 26 Weeks to 36 Weeks

Eligibility

Inclusion Criteria:

1. Preterm newborns between 26+0 and 36+6 weeks of gestation stratified in two groups:

VLBWI 26-31+6and LBWI 32-36+6.

2. Respiratory distress syndrome requiring surfactant therapy

Exclusion Criteria:

1. Need for emergency intubation in the delivery room

2. Major congenital malformations (such as cardiopathies)

3. Chromosomic abnormalities

4. Fetal Hydrops

5. Hypercapnia: CO2 > 65 mmHg

6. Pneumothorax

7. Hemodynamic compromise

Related Conditions & MeSH terms

• Premature Birth
• RDS

Intervention

Drug:
• Dexmedetomidine
administrating dexmedetomidine in order to evaluate the efficacy in achieving sedation for LISA procedure

Locations

Country	Name	City	State
Italy	Paola Lago	Treviso

Sponsors (1)

Lead Sponsor	Collaborator
University of Padova

Country where clinical trial is conducted

Italy, 

References & Publications (24)

Aldana-Aguirre JC, Pinto M, Featherstone RM, Kumar M. Less invasive surfactant administration versus intubation for surfactant delivery in preterm infants with respiratory distress syndrome: a systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed. 2017 Jan;102(1):F17-F23. doi: 10.1136/archdischild-2015-310299. Epub 2016 Nov 15. Review. — View Citation

Bourgoin L, Caeymaex L, Decobert F, Jung C, Danan C, Durrmeyer X. Administering atropine and ketamine before less invasive surfactant administration resulted in low pain scores in a prospective study of premature neonates. Acta Paediatr. 2018 Jul;107(7):1184-1190. doi: 10.1111/apa.14317. Epub 2018 Apr 16. — View Citation

Chevallier M, Durrmeyer X, Ego A, Debillon T; PROLISA Study Group. Propofol versus placebo (with rescue with ketamine) before less invasive surfactant administration: study protocol for a multicenter, double-blind, placebo controlled trial (PROLISA). BMC Pediatr. 2020 May 8;20(1):199. doi: 10.1186/s12887-020-02112-x. — View Citation

COMMITTEE ON FETUS AND NEWBORN and SECTION ON ANESTHESIOLOGY AND PAIN MEDICINE. Prevention and Management of Procedural Pain in the Neonate: An Update. Pediatrics. 2016 Feb;137(2):e20154271. doi: 10.1542/peds.2015-4271. Epub 2016 Jan 25. — View Citation

Dekker J, Lopriore E, Rijken M, Rijntjes-Jacobs E, Smits-Wintjens V, Te Pas A. Sedation during Minimal Invasive Surfactant Therapy in Preterm Infants. Neonatology. 2016;109(4):308-13. doi: 10.1159/000443823. Epub 2016 Feb 24. — View Citation

Dekker J, Lopriore E, van Zanten HA, Tan RNGB, Hooper SB, Te Pas AB. Sedation during minimal invasive surfactant therapy: a randomised controlled trial. Arch Dis Child Fetal Neonatal Ed. 2019 Jul;104(4):F378-F383. doi: 10.1136/archdischild-2018-315015. Epub 2018 Aug 1. — View Citation

Descamps CS, Chevallier M, Ego A, Pin I, Epiard C, Debillon T. Propofol for sedation during less invasive surfactant administration in preterm infants. Arch Dis Child Fetal Neonatal Ed. 2017 Sep;102(5):F465. doi: 10.1136/archdischild-2017-312791. Epub 2017 May 8. — View Citation

Eichenwald EC; Committee on Fetus and Newborn, American Academy of Pediatrics. Apnea of Prematurity. Pediatrics. 2016 Jan;137(1). doi: 10.1542/peds.2015-3757. Epub 2015 Dec 1. — View Citation

Fischer HS, Bührer C. Avoiding endotracheal ventilation to prevent bronchopulmonary dysplasia: a meta-analysis. Pediatrics. 2013 Nov;132(5):e1351-60. doi: 10.1542/peds.2013-1880. Epub 2013 Oct 21. Review. — View Citation

Foglia EE, Ades A, Sawyer T, Glass KM, Singh N, Jung P, Quek BH, Johnston LC, Barry J, Zenge J, Moussa A, Kim JH, DeMeo SD, Napolitano N, Nadkarni V, Nishisaki A; NEAR4NEOS Investigators. Neonatal Intubation Practice and Outcomes: An International Registry Study. Pediatrics. 2019 Jan;143(1). pii: e20180902. doi: 10.1542/peds.2018-0902. Epub 2018 Dec 11. — View Citation

Isayama T, Iwami H, McDonald S, Beyene J. Association of Noninvasive Ventilation Strategies With Mortality and Bronchopulmonary Dysplasia Among Preterm Infants: A Systematic Review and Meta-analysis. JAMA. 2016 Aug 9;316(6):611-24. doi: 10.1001/jama.2016.10708. Review. Erratum in: JAMA. 2016 Sep 13;316(10):1116. — View Citation

Jensen EA, DeMauro SB, Kornhauser M, Aghai ZH, Greenspan JS, Dysart KC. Effects of Multiple Ventilation Courses and Duration of Mechanical Ventilation on Respiratory Outcomes in Extremely Low-Birth-Weight Infants. JAMA Pediatr. 2015 Nov;169(11):1011-7. doi: 10.1001/jamapediatrics.2015.2401. — View Citation

Kribs A, Roll C, Göpel W, Wieg C, Groneck P, Laux R, Teig N, Hoehn T, Böhm W, Welzing L, Vochem M, Hoppenz M, Bührer C, Mehler K, Stützer H, Franklin J, Stöhr A, Herting E, Roth B; NINSAPP Trial Investigators. Nonintubated Surfactant Application vs Conventional Therapy in Extremely Preterm Infants: A Randomized Clinical Trial. JAMA Pediatr. 2015 Aug;169(8):723-30. doi: 10.1001/jamapediatrics.2015.0504. — View Citation

Kribs A. Minimally Invasive Surfactant Therapy and Noninvasive Respiratory Support. Clin Perinatol. 2016 Dec;43(4):755-771. doi: 10.1016/j.clp.2016.07.010. Epub 2016 Oct 14. Review. — View Citation

Kumar P, Denson SE, Mancuso TJ; Committee on Fetus and Newborn, Section on Anesthesiology and Pain Medicine. Premedication for nonemergency endotracheal intubation in the neonate. Pediatrics. 2010 Mar;125(3):608-15. doi: 10.1542/peds.2009-2863. Epub 2010 Feb 22. Review. — View Citation

Lawrence J, Alcock D, McGrath P, Kay J, MacMurray SB, Dulberg C. The development of a tool to assess neonatal pain. Neonatal Netw. 1993 Sep;12(6):59-66. — View Citation

Lemyre B, Laughon M, Bose C, Davis PG. Early nasal intermittent positive pressure ventilation (NIPPV) versus early nasal continuous positive airway pressure (NCPAP) for preterm infants. Cochrane Database Syst Rev. 2016 Dec 15;12:CD005384. doi: 10.1002/14651858.CD005384.pub2. Review. — View Citation

SUPPORT Study Group of the Eunice Kennedy Shriver NICHD Neonatal Research Network, Finer NN, Carlo WA, Walsh MC, Rich W, Gantz MG, Laptook AR, Yoder BA, Faix RG, Das A, Poole WK, Donovan EF, Newman NS, Ambalavanan N, Frantz ID 3rd, Buchter S, Sánchez PJ, Kennedy KA, Laroia N, Poindexter BB, Cotten CM, Van Meurs KP, Duara S, Narendran V, Sood BG, O'Shea TM, Bell EF, Bhandari V, Watterberg KL, Higgins RD. Early CPAP versus surfactant in extremely preterm infants. N Engl J Med. 2010 May 27;362(21):1970-9. doi: 10.1056/NEJMoa0911783. Epub 2010 May 16. Erratum in: N Engl J Med. 2010 Jun 10;362(23):2235. — View Citation

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. Neonatol — View Citation

Tran DTT, Newton EK, Mount VAH, Lee JS, Mansour C, Wells GA, Perry JJ. Rocuronium vs. succinylcholine for rapid sequence intubation: a Cochrane systematic review. Anaesthesia. 2017 Jun;72(6):765-777. doi: 10.1111/anae.13903. — View Citation

Venkatraman R, Hungerford JL, Hall MW, Moore-Clingenpeel M, Tobias JD. Dexmedetomidine for Sedation During Noninvasive Ventilation in Pediatric Patients. Pediatr Crit Care Med. 2017 Sep;18(9):831-837. doi: 10.1097/PCC.0000000000001226. — View Citation

Verder H, Agertoft L, Albertsen P, Christensen NC, Curstedt T, Ebbesen F, Greisen G, Hobolth N, Holm V, Jacobsen T, et al. [Surfactant treatment of newborn infants with respiratory distress syndrome primarily treated with nasal continuous positive air pressure. A pilot study]. Ugeskr Laeger. 1992 Jul 27;154(31):2136-9. Danish. — View Citation

Weerink MAS, Struys MMRF, Hannivoort LN, Barends CRM, Absalom AR, Colin P. Clinical Pharmacokinetics and Pharmacodynamics of Dexmedetomidine. Clin Pharmacokinet. 2017 Aug;56(8):893-913. doi: 10.1007/s40262-017-0507-7. Review. — View Citation

Wyckoff MH, Aziz K, Escobedo MB, Kapadia VS, Kattwinkel J, Perlman JM, Simon WM, Weiner GM, Zaichkin JG. Part 13: Neonatal Resuscitation: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2015 Nov 3;132(18 Suppl 2):S543-60. doi: 10.1161/CIR.0000000000000267. Review. — View Citation

* Note: There are 24 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	effectiveness of dexmedetomidine in achieving sedation for LISA procedure	evaluation of changes in Neonatal Infant Pain Scale (NIPS) score (0-2 points= no pain, 3-4 points = moderate pain; > 4 = severe pain)	basal (before procedure), during and immediately after the procedure
Primary	Safety of dexmedetomidine in sedating preterm infants	evaluation of number of apneas ( > 20 seconds or < 20 seconds with bradycardia < 100 bpm or desaturation ( SpO2 < 85%)); number of severe apnea and bradycardia (defined by the American Academy of Pediatrics Guidelines as apnea > 30 seconds and/or heart rate < 60 beats/minute for more than 10 seconds); need for intubation.	24 hours
Secondary	number of laryngoscopies needed to perform LISA	calculate the number of laryngoscopies needed to perform LISA	during the procedure
Secondary	time needed to perform LISA	calculate the time needed to perform LISA	during the procedure
Secondary	Intubation conditions	evaluated by the operator using the Goldberg scale (3 = excellent intubation conditions; 4-6= good intubation conditions; 7-9 = poor intubation conditions; 10-12 = inadequate intubation conditions)	during the procedure
Secondary	the evolution of cardiorespiratory parameters	heart rate (beats per minute)	1 min, 3 min, 5 min, 15 min, 30 min, 60 min and 120 min after the first drug injection
Secondary	the evolution of cardiorespiratory parameters	respiratory rate (breaths per minute)	1 min, 3 min, 5 min, 15 min, 30 min, 60 min and 120 min after the first drug injection
Secondary	the evolution of cardiorespiratory parameters	pulse oximetry (%)	1 min, 3 min, 5 min, 15 min, 30 min, 60 min and 120 min after the first drug injection
Secondary	the evolution of cardiorespiratory parameters	blood pressure (mmHg)	1 min, 3 min, 5 min, 15 min, 30 min, 60 min and 120 min after the first drug injection
Secondary	the evolution of cardiorespiratory parameters	FiO2 maxima during the procedure maintained for at least 30 seconds (%)	1 min, 3 min, 5 min, 15 min, 30 min, 60 min and 120 min after the first drug injection
Secondary	changes in ventilation mode	inspiratory and end-expiratory ventilation pressures changes (cmH2O)	1 min, 3 min, 5 min, 15 min, 30 min, 60 min and 120 min after the first drug injection
Secondary	The incidence of drug adverse effects	respiratory events (i.e. bronchospasm) or cardiovascular events (bradycardia, hypotension)	24 hours after drug injection
Secondary	The incidence of pneumothorax or selective administration of surfactant	RX evaluation	24 hours after drug injection
Secondary	Long term outcomes	mortality (%)	at 40 weeks PMA
Secondary	Long term outcomes	bronchopulmonary dysplasia (%), defined as oxygen administration and/or respiratory support at 36 wGA	at 40 weeks PMA
Secondary	Long term outcomes	intraventricular hemorrhage (%) and periventricular leukomalacia (%)	at 40 weeks PMA
Secondary	Long term outcomes	necrotizing enterocolitis (%)	at 40 weeks PMA
Secondary	Long term outcomes	retinopathy of prematurity (%)	at 40 weeks PMA