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

Virgilio Paolo Carnielli

Status and phase: Unknown; Phase 4

Conditions: Respiratory Distress Syndrome in Premature Infants

Treatments: Drug: Analgesic, Opioid; Procedure: LISA; Procedure: INSURE

Study type: Interventional

Funder types: Other

Identifiers

NCT04073173

StrAAS

2020-004269-38 (EudraCT Number)

Details and patient eligibility

About

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.

Full description

At present, LISA and INSURE are both used for surfactant therapy in infants as comparable methods. However, a clear policy of using analgesics during surfactant therapy is still lacking: some neonatologists use analgesics to reduce stress and pain scores, whereas others do not approve their use due to interference with spontaneous breathing.

In this open-label, randomized, phase 4 clinical trial, infants admitted to our neonatal intensive unit care (NICU) will be evaluated according to the selection criteria and then randomized to receive or not remifentanil as an analgesic drug during the administration of porcine surfactant (poractant alfa, Curosurf®) via the INSURE or LISA method: Group-1) LISA-analgesic; Group 2) LISA-no analgesic; Group-3) INSURE-analgesic; Group-4) INSURE-no analgesic. Study patients will be stratified by gestational age at birth: Block A) 23.0-27.6 weeks of gestation; Block B) 28.0-31.6 weeks of gestation.

Early caffeine administration will be provided according to our NICU guidelines shortly after birth. Infants with adequate respiratory drive will be stabilized on nasal continuous positive airway pressure (CPAP; 4-8 cm of water) right after birth. Oxygen saturation targets will be 90-94%; moderate degrees of hypercarbia (PaCO2 < 60 mmHg, provided arterial pH >7.22) will be tolerated. Conditions mimicking respiratory distress syndrome (RDS; i.e. sepsis, air leaks, aspiration pneumonia, congenital heart disease) will be ruled out. RDS diagnosis will be clinical according to the European Guidelines. Nasal CPAP, bi-level CPAP or nasal intermittent positive pressure ventilation (synchronized or not) will be used at the discretion of the attending physician to stabilize the patients. Intubation criteria according to our NICU guidelines will be:

1. severe acidosis (defined as arterial pH<7.20 with a partial pressure of carbon dioxide (PaCO2) > 55 mmHg and partial pressure of oxygen (PaO2) < 50 mmHg) with a fraction of inspired oxygen (FiO2) > 0.50;
2. severe apnoea.

Enrolled infants will be evaluated from birth to day 7 of the hospital stay.

Enrollment: 80 estimated patients

Sex: All

Ages: 168 to 223 days old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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80 participants in 4 patient groups

LISA-analgesic

Experimental group

Description:

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

Treatment:

Procedure: LISA

Drug: Analgesic, Opioid

LISA-no analgesic

Experimental group

Description:

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

Treatment:

Procedure: LISA

INSURE-analgesic

Experimental group

Description:

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

Treatment:

Procedure: INSURE

Drug: Analgesic, Opioid

INSURE-no analgesic

Experimental group

Description:

INSURE without an analgesic drug.

Treatment:

Procedure: INSURE