Premedication for Neonatal Respiratory Distress Syndrome

(PRELISA Trial)

Recruiting in Palo Alto (17 mi)

Age: < 18

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: University of Texas Southwestern Medical Center

Disqualifiers: Severe congenital anomalies, Opioid addiction, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial tests if giving preterm infants fentanyl and atropine before a lung treatment can reduce the risk of low heart rate and low oxygen levels. The study focuses on infants born prematurely who have breathing problems. Fentanyl has been studied for its potential to reduce stress and improve outcomes in these infants.

Will I have to stop taking my current medications?

The trial information does not specify whether participants must stop taking their current medications.

What data supports the effectiveness of the drug IV Atropine and Fentanyl for treating Neonatal Respiratory Distress Syndrome?

Research shows that fentanyl, when used in infants with respiratory distress syndrome, can reduce stress and improve outcomes. Additionally, premedication with atropine and fentanyl before procedures like intubation helps reduce pain and stabilize vital signs in newborns. ^{1 2 3 4 5}

Is the combination of atropine and fentanyl safe for use in humans?

The combination of atropine and fentanyl has been used safely in various medical procedures, including neonatal intubation and pediatric sedation, with minimal side effects when administered by qualified professionals. However, some adverse effects like chest wall rigidity and respiratory issues have been noted, emphasizing the need for careful monitoring. ^{3 4 5 6 7}

How does the drug combination of IV Atropine and Fentanyl differ from other treatments for neonatal respiratory distress syndrome?

The combination of IV Atropine and Fentanyl is unique because it is used as premedication to reduce pain and stabilize vital signs during intubation in newborns, which is not a standard treatment for neonatal respiratory distress syndrome itself. This approach helps minimize adverse physiological responses and discomfort during the procedure. ^{3 5 6 7 8}

Research Team

Venkatakrishna Kakkilaya, MD

Principal Investigator

UT Southwestern Medical Center

Eligibility Criteria

The PRELISA trial is for preterm infants aged between 0-72 hours, at least 29 weeks gestational age, needing CPAP respiratory support and qualifying for the LISA procedure. It excludes those with severe congenital anomalies, born to mothers with opioid addiction or on methadone treatment, or requiring intubation before surfactant therapy.

Inclusion Criteria

My baby is on CPAP for breathing support and qualifies for the LISA procedure.

Exclusion Criteria

My infant has severe birth defects, including heart, airway, or brain issues.

Babies born to mothers who are addicted to opioids or are in a methadone treatment program.

My infant needed a breathing tube before receiving surfactant treatment.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either IV atropine and fentanyl or placebo prior to the Less Invasive Surfactant Administration (LISA) procedure

Immediate (single procedure)

1 visit (in-person)

Observation

Participants are monitored for bradycardia and hypoxemia events during and immediately after the LISA procedure

12 hours

Follow-up

Participants are monitored for safety and effectiveness, including intubation rates and cerebral oxygenation, after the procedure

24 hours

Treatment Details

Interventions

• IV Atropine and Fentanyl (Other)

Trial Overview This study tests if IV fentanyl and atropine given before the LISA procedure can reduce bradycardia and hypoxemia events in preterm infants compared to a placebo. The trial is double-blinded and randomized; success rates of the first attempt and effects on cerebral oxygenation are also measured.

Participant Groups

Group I: IV Atropine and Fentanyl Premedication Arm Experimental Treatment 1 Intervention

Participants will receive premedication regimen of 20 micrograms/kilogram intravenous atropine and 0.5 micrograms/kilogram intravenous fentanyl prior to performance of LISA.

Group II: IV Normal Saline Placebo Arm Placebo Group 1 Intervention

Participants will receive two intravenous Normal Saline infusions in quantities equivalent to the calculated volumes of atropine and fentanyl for participant's weight prior to performance of LISA.

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Daniel K. Podolsky

University of Texas Southwestern Medical Center

Chief Executive Officer since 2008

MD from Harvard Medical School

Robert L. Bass

University of Texas Southwestern Medical Center

Chief Medical Officer since 2019

MD from University of Texas Southwestern Medical School

Chiesi Farmaceutici S.p.A.

Industry Sponsor

Trials

206

Recruited

315,000+

Founded

1935

Headquarters

Parma, Italy

Known For

Respiratory diseases

Top Products

NEXThaler, Trimbow, Curosurf, Holoclar

Findings from Research

Premature infants receiving fentanyl infusions showed reduced stress indicators, such as lower behavioral state scores and heart rates, compared to those receiving a placebo, suggesting some immediate benefits of fentanyl in managing stress during respiratory distress syndrome.

However, despite these stress reductions, fentanyl did not improve long-term outcomes or catabolic states, and infants on fentanyl required higher levels of ventilatory support, indicating potential complications associated with its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Routine use of fentanyl infusions for pain and stress reduction in infants with respiratory distress syndrome. Orsini, AJ., Leef, KH., Costarino, A., et al.[2022]

In a study of 27 preterm infants receiving low-dose fentanyl infusion for 75 hours, the treatment significantly reduced behavioral stress scores and oxygen desaturations compared to a control group of 28 untreated infants.

The fentanyl infusion also lowered urinary levels of stress-related hormones (metanephrine and normetanephrine), indicating a reduced neuroendocrine stress response, although there were no significant differences in ventilatory variables or short-term outcomes between the two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomised controlled trial of low dose fentanyl infusion in preterm infants with hyaline membrane disease. Lago, P., Benini, F., Agosto, C., et al.[2022]

Premedication with analgesics and vagolytics is essential for newborns undergoing endotracheal intubation, as it significantly reduces pain and adverse physiological responses such as bradycardia and hypoxia.

An optimal premedication protocol includes IV atropine, IV fentanyl, and IV succinylcholine, and intubations should be conducted by trained personnel with careful monitoring of the infant's condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Premedication for endotracheal intubation in the newborn infant. Barrington, K.[2021]

In a study of 40 newborn and premature infants on artificial ventilation for severe respiratory distress syndrome, those receiving fentanyl required significantly less sedatives and catecholamines, indicating its efficacy in managing pain and sedation.

Fentanyl did not significantly affect heart rate or blood pressure, but it was associated with delayed meconium excretion and earlier peaks in bilirubin levels, suggesting careful monitoring is necessary when using it in neonatal care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analgesia and sedation in neonatal intensive care using fentanyl by continuous infusion. Roth, B., Schlünder, C., Houben, F., et al.[2019]

In a study of 27 healthy children aged around 34 months, IV sedation using ketamine and fentanyl was found to be safe and effective, with stable vital signs throughout the procedure.

While there were some side effects, such as nausea (22%) and vomiting (15%), the overall sedation method showed minimal complications, making it a viable alternative to general anesthesia for pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IV sedation in pediatric dentistry: an alternative to general anesthesia. Barr, EB., Wynn, RL.[2013]

In a study of 269 neonatal endotracheal intubations, the use of routine premedication with atropine, fentanyl, and succinylcholine was found to be safe and effective, with all infants successfully intubated.

The premedication policy resulted in a majority of successful intubations on the first attempt, highlighting its feasibility and humane approach in neonatal care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Premedication for neonatal intubation. Barrington, KJ., Byrne, PJ.[2013]

In a study of 54 neonates undergoing elective intubation, the combination of remifentanil and atropine resulted in excellent or good intubating conditions in 85% of cases, indicating its efficacy as a premedication.

However, the use of remifentanil was associated with significant adverse effects, including chest wall rigidity in 11% of procedures and respiratory complications in 9%, raising concerns about its safety for neonates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety Aspects of Remifentanil Sedation for Intubation in Neonates: A Retrospective Study. Chollat, C., Maroni, A., Aubelle, MS., et al.[2020]

In a study of 60 preterm infants, the use of atropine, fentanyl, and succinylcholine before intubation resulted in a median of 2 attempts, with 91.7% of cases achieving excellent or good intubation conditions.

Infants who received succinylcholine had fewer intubation attempts (median of 1) compared to those who did not, and no serious adverse events were reported, indicating a safe and effective premedication strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atropine, fentanyl and succinylcholine for non-urgent intubations in newborns. Lemyre, B., Cheng, R., Gaboury, I.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Routine use of fentanyl infusions for pain and stress reduction in infants with respiratory distress syndrome. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Randomised controlled trial of low dose fentanyl infusion in preterm infants with hyaline membrane disease. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Premedication for endotracheal intubation in the newborn infant. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Analgesia and sedation in neonatal intensive care using fentanyl by continuous infusion. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

IV sedation in pediatric dentistry: an alternative to general anesthesia. [2013]

6. United States pubmed.ncbi.nlm.nih.gov

Premedication for neonatal intubation. [2013]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and Safety Aspects of Remifentanil Sedation for Intubation in Neonates: A Retrospective Study. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Atropine, fentanyl and succinylcholine for non-urgent intubations in newborns. [2019]