Vasopressin vs. Epinephrine for Neonatal Cardiac Arrest

Recruiting in Edmonton (>99 mi)

Overseen By Georg Schmolzer, MD, PhD

Age: < 18

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Alberta

Disqualifiers: Congenital heart disease, Breathing conditions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: up to 60 minutes

20 Participants Needed

Trial Summary

What is the purpose of this trial?

When a baby is born with a low heart rate or no heart rate, the clinical team must provide breathing support and chest compressions (what is call cardiopulmonary resuscitation or CPR). In some situations, the clinical team also need to give medications to help the heart rate increase. During CPR, the most common medication given is called epinephrine. There is another medication called vasopressin that is available that could be beneficial to newborn babies. However, no study has compared epinephrine with vasopressin in the delivery room during neonatal CPR. The current study will be the first trial comparing this two medications during neonatal CPR. The investigators will randomize our hospital to either epinephrine or vasopressin for the duration of one year. Babies will either receive CPR with epinephrine (this will be the control group) or CPR with vasopressin ( this will be the intervention group). The investigators believe that vasopressin may be more helpful to babies with a low heartrate or no heart rate at birth.

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 epinephrine compared to vasopressin for neonatal cardiac arrest?

Research shows that epinephrine is more effective than vasopressin in achieving the return of spontaneous circulation (ROSC) in newborn animal models with cardiac arrest. In a study with fetal lambs, epinephrine led to a quicker and more frequent ROSC compared to vasopressin, supporting its use in neonatal resuscitation. ^{1 2 3 4 5}

Is vasopressin safe compared to epinephrine for neonatal cardiac arrest?

Epinephrine is the recommended treatment for neonatal cardiac arrest, as it has been shown to be more effective than vasopressin in animal studies. Vasopressin has not been proven safe or effective for newborns, and there is insufficient evidence to recommend its use in this age group. ^{1 2 3 6 7}

How does the drug vasopressin compare to epinephrine for neonatal cardiac arrest?

Vasopressin is being studied as an alternative to epinephrine for neonatal cardiac arrest, but current research suggests that epinephrine is more effective in achieving a quicker return of spontaneous circulation (ROSC). Vasopressin acts as a systemic vasoconstrictor, which can increase blood flow in the lungs, but it has shown a lower success rate and longer time to ROSC compared to epinephrine in animal studies. ^{1 2 3 5 8}

Research Team

Georg Schmolzer

Principal Investigator

University of Alberta

Eligibility Criteria

This trial is for newborn babies, both full-term and preterm, who are born with a very low heart rate or no heart rate at all. Babies with congenital heart defects like hypo-plastic left heart or conditions that affect breathing such as congenital diaphragmatic hernia cannot participate.

Inclusion Criteria

My baby was born without a heartbeat or with a very slow heart rate.

Exclusion Criteria

I was born with a heart condition.

I have a condition that makes it hard for me to breathe.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either epinephrine or vasopressin during neonatal CPR, with chest compressions and medication administration as per resuscitation guidelines.

up to 60 minutes

In-hospital during delivery

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of mortality, brain injury, and other health parameters.

30 weeks

Regular hospital visits until discharge

Treatment Details

Interventions

• Epinephrine
• Vasopressin

Trial Overview The study compares two medications used during CPR in newborns: vasopressin and epinephrine. Hospitals will use one of these drugs for a year when performing CPR on babies with low or no heartbeat at birth. The goal is to see if vasopressin offers more benefits than the commonly used epinephrine.

Participant Groups

Group I: Vasopressin Experimental Treatment 1 Intervention

"Vasopressin group" Vasopressin will be via umbilical vein catheter (0.4 IU/kg per dose - first line) or alternatively via an endotracheal tube (8 IU/kg) every three to five minutes as needed with a maximum of two doses if there is no ROSC \[2,3\] After that, the clinical team must convert to give epinephrine (0.02 mg/kg per dose) as long as CPR is ongoing.

Group II: Epinephrine Active Control 1 Intervention

Epinephrine group" Epinephrine will be administered according to current resuscitation guidelines either via umbilical vein catheter (0.02 mg/kg per dose) or via endotracheal tube (0.1 mg/kg) every three to five minutes as needed\[2,3\]. Chest compressions and epinephrine will be continued until ROSC.

Epinephrine is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Epinephrine for:

• Anaphylaxis
• Cardiac arrest
• Severe allergic reactions

Approved in United States as Epinephrine for:

• Anaphylaxis
• Cardiac arrest
• Severe allergic reactions

Approved in Canada as Epinephrine for:

• Anaphylaxis
• Cardiac arrest
• Severe allergic reactions

Who Is Running the Clinical Trial?

University of Alberta

Lead Sponsor

Trials

957

Recruited

437,000+

Findings from Research

This pilot trial will compare the efficacy of vasopressin versus epinephrine in neonatal CPR, focusing on the time to return of spontaneous circulation (ROSC) in asphyxiated newborns, with an estimated 20 participants.

The study aims to provide valuable data on optimal vasopressor therapy during neonatal resuscitation, addressing the high rates of mortality and neurodevelopmental disability associated with current practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vasopressin versus epinephrine during cardiopulmonary resuscitation of asphyxiated newborns: A study protocol for a prospective, cluster, open label, single-center, randomized controlled phase 2 trial - The VERSE-Trial. Ramsie, M., Cheung, PY., Law, B., et al.[2023]

In a study involving 27 term fetal lambs with cardiac arrest induced by umbilical cord occlusion, epinephrine was more effective than vasopressin, achieving return of spontaneous circulation (ROSC) in 7 out of 10 lambs within an average of 8 minutes, while vasopressin only achieved ROSC in 3 out of 9 lambs after an average of 13 minutes.

The findings support current neonatal resuscitation guidelines that recommend the exclusive use of epinephrine, as vasopressin resulted in a lower incidence and longer time to ROSC, indicating it may not be suitable for this purpose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Masked Randomized Trial of Epinephrine versus Vasopressin in an Ovine Model of Perinatal Cardiac Arrest. Rawat, M., Gugino, S., Koenigsknecht, C., et al.[2023]

In a study involving newborn piglets, vasopressin showed similar effectiveness to epinephrine in achieving return of spontaneous circulation (ROSC) after asphyxial cardiac arrest, with no significant differences in time to ROSC or incidence of ROSC among the groups.

However, piglets treated with vasopressin had a trend towards lower time to ROSC and higher post-ROSC survival rates compared to those treated with epinephrine, suggesting that vasopressin may offer potential benefits that warrant further investigation in human neonatal trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of various vasopressin doses to epinephrine during cardiopulmonary resuscitation in asphyxiated neonatal piglets. Ramsie, M., Cheung, PY., Lee, TF., et al.[2023]

In a study involving 67 young swine, vasopressin was found to significantly improve coronary perfusion pressure (CoPP) and cerebral blood flow (CBF) more effectively than a second dose of epinephrine after initial doses were ineffective.

Among the swine that did not respond to two doses of epinephrine, 45% were able to achieve the target CoPP of ≥20 mmHg with a single dose of vasopressin, highlighting its potential as a more effective rescue therapy in pediatric cardiac arrest scenarios.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The physiologic response to rescue therapy with vasopressin versus epinephrine during experimental pediatric cardiac arrest. Slovis, JC., Morgan, RW., Landis, WP., et al.[2022]

In a study involving 69 neonatal pigs, vasopressin significantly improved survival rates after cardiac arrest compared to control and low-dose epinephrine, suggesting it may be a more effective treatment in resuscitation scenarios.

Vasopressin also resulted in lower levels of post-resuscitation troponin, indicating less heart damage, and showed better hemodynamic stability compared to epinephrine, highlighting its potential for use in human neonates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vasopressin improves survival compared with epinephrine in a neonatal piglet model of asphyxial cardiac arrest. McNamara, PJ., Engelberts, D., Finelli, M., et al.[2014]

In a study involving 18 piglets, the combination of epinephrine and vasopressin during cardiopulmonary resuscitation (CPR) significantly improved left ventricular blood flow compared to using vasopressin or epinephrine alone, indicating a more effective treatment strategy for ventricular fibrillation.

Both vasopressin alone and the combination with epinephrine enhanced total cerebral blood flow during CPR, suggesting that vasopressin may have beneficial effects in pediatric patients experiencing ventricular fibrillation, unlike its poorer outcomes in asphyxial cardiac arrest.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of epinephrine and vasopressin in a piglet model of prolonged ventricular fibrillation and cardiopulmonary resuscitation. Voelckel, WG., Lurie, KG., McKnite, S., et al.[2019]

Epinephrine is the main medication used for neonatal resuscitation in cases of asystole or prolonged bradycardia, as it effectively increases coronary perfusion pressure through peripheral vasoconstriction.

Current guidelines recommend intravenous administration of epinephrine at doses of 0.01-0.03 mg/kg, while high-dose intravenous epinephrine does not improve long-term survival and poses additional risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medications in neonatal resuscitation: epinephrine and the search for better alternative strategies. Weiner, GM., Niermeyer, S.[2013]

In a study of 727 cardiac arrest patients, vasopressin showed a statistically significant improvement in survival to hospital admission (22.2%) compared to adrenaline (16.7%), particularly in cases of prolonged cardiac arrest.

However, there was no significant difference in long-term survival to hospital discharge between the two treatments, indicating that while vasopressin may help in the short term, it does not lead to better overall outcomes compared to adrenaline.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomised, double-blind, multi-centre trial comparing vasopressin and adrenaline in patients with cardiac arrest presenting to or in the Emergency Department. Ong, ME., Tiah, L., Leong, BS., et al.[2013]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Vasopressin versus epinephrine during cardiopulmonary resuscitation of asphyxiated newborns: A study protocol for a prospective, cluster, open label, single-center, randomized controlled phase 2 trial - The VERSE-Trial. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Masked Randomized Trial of Epinephrine versus Vasopressin in an Ovine Model of Perinatal Cardiac Arrest. [2023]

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

Comparison of various vasopressin doses to epinephrine during cardiopulmonary resuscitation in asphyxiated neonatal piglets. [2023]

4. Netherlands pubmed.ncbi.nlm.nih.gov

The physiologic response to rescue therapy with vasopressin versus epinephrine during experimental pediatric cardiac arrest. [2022]

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

Vasopressin improves survival compared with epinephrine in a neonatal piglet model of asphyxial cardiac arrest. [2014]

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

Effects of epinephrine and vasopressin in a piglet model of prolonged ventricular fibrillation and cardiopulmonary resuscitation. [2019]

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

Medications in neonatal resuscitation: epinephrine and the search for better alternative strategies. [2013]

8. Ireland pubmed.ncbi.nlm.nih.gov

A randomised, double-blind, multi-centre trial comparing vasopressin and adrenaline in patients with cardiac arrest presenting to or in the Emergency Department. [2013]