Stress Assessment With and Without Analgesia During Surfactant Therapy in Preterm Infants.

NCT04073173 | Unknown Phase 4

• 2 other identifiers: StrAAS2020-004269-38
• Study Type: interventional
• Target: 80
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study will compare stress, changes in oxygenation and oxidative damage in preterm infants with respiratory distress syndrome (RDS) randomized to receive or not remifentanil as an analgesic drug during the administration of porcine surfactant (poractant alfa, Curosurf®) through the traditional (INSURE) or the less invasive (LISA) method.

Conditions

Respiratory Distress Syndrome in Premature Infants

Keywords

RDS; Preterm Infants; Surfactant; LISA; INSURE; Analgesia; Stress

Outcome Measures

Primary Outcomes (1)

• Cortisol concentrations

  Cortisol concentrations will be assessed in saliva, as salivary cortisol levels have been shown to be useful surrogate markers for plasma cortisol levels in neonates. Saliva samples will be collected using an absorbent swab stick, centrifuged at 4000 rpm for 10 minutes and kept at -80°C until assayed (minimum sample volume 25 µl). Enzyme immunoassay (ELISA kit) will be used. Basal samples will be obtained at the hospital admission and right before surfactant.

  At 1, 3, 6 12, 24 hours after surfactant administration and then daily in the first week at the same time of the day (to avoid circadian variations).

Secondary Outcomes (5)

• Galvanic Skin Responses

  At 1, 3, 6 12, 24 hours after surfactant administration and then daily in the first week at the same time of the day (to avoid circadian variations).

• Heart rate

  6 hours before and after surfactant therapy will be analyzed.

• Brain oxygenation

  From the hospital admission to day 7 of the hospital stay.

• Oxygen saturation (SpO2)

  From the hospital admission to day 7 of the hospital stay.

• Markers of oxidative stress

  At the hospital admission and at 6 and 12 hours after surfactant therapy.

Study Arms (4)

LISA-analgesic

EXPERIMENTAL

Less Invasive Surfactant Administration (LISA) with remifentanil (0.5-2 micrograms/kg/dose) as the analgesic drug.

Procedure: LISA; Drug: Analgesic, Opioid

LISA-no analgesic

EXPERIMENTAL

Less Invasive Surfactant Administration (LISA) without an analgesic drug.

Procedure: LISA

INSURE-analgesic

EXPERIMENTAL

INtubation-SURfactant-Extubation (INSURE) with remifentanil (0.5-2 micrograms/kg/dose) as the analgesic drug.

Procedure: INSURE; Drug: Analgesic, Opioid

INSURE-no analgesic

EXPERIMENTAL

INSURE without an analgesic drug.

Procedure: INSURE

Interventions

INSURE PROCEDURE

Patients will be intubated by endotracheal tube, exogenous surfactant (Poractant alfa) will be administered and then they will be extubated.

INSURE-analgesic; INSURE-no analgesic

LISA PROCEDURE

Surfactant (Poractant alfa) will be directly delivered into the lungs via a fine bore catheter inserted into the trachea and then patients will be extubated.

LISA-analgesic; LISA-no analgesic

Analgesic, Opioid DRUG

Remifentanil (0.5-2 micrograms/kg/dose)

INSURE-analgesic; LISA-analgesic

Eligibility Criteria

• Age: 168 Days - 223 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• gestational age at birth between 168 and 223 days,
• respiratory distress syndrome (diagnosed on the basis of clinical and/or radiological grounds) with a fraction of inspired oxygen ≥0.30 (for infants born ≤26 weeks' gestational age) or ≥0.40 (for infants born \>26 weeks' gestational age) to achieve a peripheral oxygen saturation of 90-94% within 24 hours of life and good respiratory drive,
• written informed consent.

You may not qualify if:

• major malformations,
• late admission (after 24 hours of life),
• intubation in the delivery room,
• severe birth asphyxia,
• prolonged rupture of membranes,
• air leaks,
• no informed consent.

Sponsors & Collaborators

• Virgilio Paolo Carnielli: lead
• Fondazione Cassa di Risparmio di Verona Vicenza Belluno e Ancona: collaborator
• Istituto di Ricerca Pediatrica Città della Speranza: collaborator

Related Publications (6)

• Sweet DG, Carnielli V, Greisen G, Hallman M, Ozek E, Plavka R, Saugstad OD, Simeoni U, Speer CP, Vento M, Visser GH, Halliday HL. European Consensus Guidelines on the Management of Respiratory Distress Syndrome - 2016 Update. Neonatology. 2017;111(2):107-125. doi: 10.1159/000448985. Epub 2016 Sep 21.

  PMID: 27649091 BACKGROUND

• Okamura H, Kinoshita M, Saitsu H, Kanda H, Iwata S, Maeno Y, Matsuishi T, Iwata O. Noninvasive surrogate markers for plasma cortisol in newborn infants: utility of urine and saliva samples and caution for venipuncture blood samples. J Clin Endocrinol Metab. 2014 Oct;99(10):E2020-4. doi: 10.1210/jc.2014-2009. Epub 2014 Jul 31.

  PMID: 25078034 BACKGROUND

• Lago P, Benini F, Agosto C, Zacchello F. Randomised controlled trial of low dose fentanyl infusion in preterm infants with hyaline membrane disease. Arch Dis Child Fetal Neonatal Ed. 1998 Nov;79(3):F194-7. doi: 10.1136/fn.79.3.f194.

  PMID: 10194990 BACKGROUND

• Guinsburg R, Kopelman BI, Anand KJ, de Almeida MF, Peres Cde A, Miyoshi MH. Physiological, hormonal, and behavioral responses to a single fentanyl dose in intubated and ventilated preterm neonates. J Pediatr. 1998 Jun;132(6):954-9. doi: 10.1016/s0022-3476(98)70390-7.

  PMID: 9627585 BACKGROUND

• Guinsburg R, Kopelman BI, de Almeida MF, Miyoshi MH. [Pain in intubated and ventilated preterm neonate: multidimensional assessment and response to fentanyl analgesia]. J Pediatr (Rio J). 1994 Mar-Apr;70(2):82-90. doi: 10.2223/jped.727. Portuguese.

  PMID: 14688879 BACKGROUND

• Badiee Z, Vakiliamini M, Mohammadizadeh M. Remifentanil for endotracheal intubation in premature infants: A randomized controlled trial. J Res Pharm Pract. 2013 Apr;2(2):75-82. doi: 10.4103/2279-042X.117387.

  PMID: 24991608 BACKGROUND

MeSH Terms

Conditions

Respiratory Distress Syndrome In Premature Infants; Agnosia

Interventions

Insure Cement; Analgesics, Opioid

Condition Hierarchy (Ancestors)

Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Narcotics; Central Nervous System Depressants; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Central Nervous System Agents; Therapeutic Uses

Study Officials

• Virgilio Carnielli, MD, PHD

  Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona

  STUDY DIRECTOR

• Clementina Rondina, MD

  Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Virgilio Carnielli, MD, PHD

CONTACT

+390715962045; v.carnielli@staff.univpm.it

Clementina Rondina, MD

CONTACT

+390715962014; clementina.rondina@ospedaliriuniti.marche.it

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Participants and data analyst will be masked.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of Neonatology

Study Record Dates

• First Submitted: August 27, 2019
• First Posted: August 29, 2019
• Study Start: November 1, 2020
• Primary Completion: October 31, 2022
• Study Completion: October 31, 2022
• Last Updated: September 3, 2020

Record last verified: 2020-09