Premedication for Neonatal Respiratory Distress Syndrome

(PRELISA Trial)

Overseen By Venkatakrishna Kakkilaya, MD

Age: < 18

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Texas Southwestern Medical Center

Disqualifiers: Severe congenital anomalies, Opioid addiction, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: Immediate (single procedure)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates whether administering a combination of two medicines, IV atropine and IV fentanyl, to preterm infants before a procedure called Less Invasive Surfactant Administration (LISA) can enhance safety and effectiveness. The researchers aim to determine if these medicines can reduce incidents of low heart rate and low oxygen levels during LISA, improve the procedure's success rate, and influence the need for additional breathing support. Babies born at 29 weeks or later, who are on CPAP (a type of gentle breathing support) and require extra oxygen, may be suitable for this study. Participants will be randomly assigned to receive either the medication or a placebo (a harmless substance with no active ingredients) before the procedure. As a Phase 4 trial, this study involves an FDA-approved treatment and seeks to understand how it can benefit more patients.

Will I have to stop taking my current medications?

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

What is the safety track record for IV atropine and fentanyl premedication?

Research has shown that a combination of IV atropine and fentanyl is generally safe for infants. In past studies, when newborns received fentanyl nasally for procedures like intubation, no negative effects occurred. This suggests that fentanyl, when administered in controlled amounts, is safe for infants.

Fentanyl has also been used in premature infants needing assistance with breathing due to respiratory distress syndrome. Research indicates it does not cause long-term problems. Atropine, often used to control heart rate during procedures, has a strong safety record in other medical contexts.

Since this trial is in a later phase, there is already a strong understanding of the safety of these medications in similar situations. This suggests that infants in the study are likely to tolerate the treatment well. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Most treatments for neonatal respiratory distress syndrome (RDS) involve surfactant therapy or mechanical ventilation to help newborns breathe. But the combination of IV atropine and fentanyl offers a unique approach as a premedication regimen before a less invasive surfactant administration (LISA) procedure. Atropine is used to reduce secretions and prevent bradycardia, while fentanyl provides pain relief, making the procedure smoother and more comfortable for the infant. Researchers are excited because this combination could reduce the stress and potential complications associated with traditional methods, potentially leading to better outcomes for these vulnerable patients.

What evidence suggests that this premedication is effective for neonatal respiratory distress syndrome?

Research has shown that administering IV atropine and fentanyl before the Less Invasive Surfactant Administration (LISA) procedure in premature babies can reduce the risk of slow heart rate and low oxygen levels. In this trial, some participants will receive this combination as premedication. Studies with newborns have found that fentanyl does not cause harmful effects, indicating its safety. Atropine, when combined with fentanyl, helps maintain steady heart rate and blood pressure during the procedure. These medications are believed to increase the likelihood of a successful first attempt. Overall, this combination is thought to enhance the safety and effectiveness of the procedure for babies with breathing problems. ^{1 2 4 6 7}

Who Is on the Research Team?

Venkatakrishna Kakkilaya, MD

Principal Investigator

UT Southwestern Medical Center

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• IV Atropine and Fentanyl

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.

How Is the Trial Designed?

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+

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

Published Research Related to This Trial

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 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 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]

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]

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 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]

Citations

1. withpower.com withpower.com/trial/phase-4-respiratory-distress-syndrome-newborn-2022-17998

Premedication for Neonatal Respiratory Distress Syndrome 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.

2. publications.aap.org publications.aap.org/neoreviews/article/24/12/e783/195848/Pharmacologic-Adjuncts-for-Neonatal-Tracheal

Pharmacologic Adjuncts for Neonatal Tracheal Intubation In a study of neonates receiving intranasal fentanyl for various procedures including intubation, no adverse effects were reported. (38) However ...

3. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2679941

Effect of Atropine-Propofol vs Atracurium-Sufentanil on ... Main Outcomes and Measures The primary outcome was prolonged desaturation (Spo2 <80% lasting > 60 seconds), using intention-to-treat analysis ...

4. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK577837/

Evidence reviews for sedation and analgesia Very low quality evidence from 5 RCTs (n=1065) showed no clinically significant difference in mortality prior to discharge among preterm babies of all ...

5. ijn.mums.ac.ir ijn.mums.ac.ir/article_21456_a8cc6b1991532af95749ac9d028959dd.pdf

Comparison of the Effect of Remifentanil Plus Atropine with ... The use of remifentanil or remifentanil with atropine or fentanyl has no significant effect on the blood pressure and heart rate of neonates in non-emergency.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7388902/

Opioids for neonates receiving mechanical ventilation - PMC Lago assessed the respiratory dynamics in preterm infants ventilated for respiratory distress syndrome under continuous infusion of fentanyl.

7. frontiersin.org frontiersin.org/journals/pain-research/articles/10.3389/fpain.2022.836705/full

Fentanyl Exposure in Preterm Infants: Five-Year ... Our findings confirm a high risk of depression in survivors of neonatal intensive care; however, fentanyl does not appear to be a driver of this risk. Post- ...