Vasopressin vs. Epinephrine for Neonatal Cardiac Arrest

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares two medications, epinephrine (adrenaline) and vasopressin, used during CPR for newborns with a very low or no heart rate at birth. The goal is to determine if vasopressin is more effective than the commonly used epinephrine in these critical situations. Newborns eligible for this trial are those born without a heartbeat or with a very slow heart rate, excluding those with certain heart conditions or breathing issues. By testing these medications, researchers aim to improve survival and recovery outcomes for these infants. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering a unique opportunity to be among the first to receive this potentially groundbreaking treatment.

Will I have to stop taking my current medications?

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

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that vasopressin might be a promising alternative to epinephrine during CPR (cardiopulmonary resuscitation) for newborns. Studies have found that vasopressin can improve survival rates in newborns and cause less heart damage compared to epinephrine. Tests with newborn piglets demonstrated that vasopressin led to better outcomes, such as a quicker return of a heartbeat and less stress on the heart.

Epinephrine remains a well-known and commonly used treatment during CPR. It is generally considered safe, but researchers are exploring whether vasopressin could yield better results.

Both treatments appear well-tolerated in emergency situations like CPR. However, the potential benefits of vasopressin for newborns continue to be studied. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatment for neonatal cardiac arrest, which typically involves epinephrine, researchers are investigating vasopressin for its potential to improve outcomes. Vasopressin is unique because it works differently from epinephrine; it directly targets blood vessels to increase blood flow without the strong adrenaline effects. This difference in action could mean better stabilization of newborns during resuscitation. Researchers are excited because if vasopressin proves effective, it could significantly enhance recovery rates in these critical situations.

What evidence suggests that this trial's treatments could be effective for neonatal cardiac arrest?

This trial will compare the effectiveness of vasopressin and epinephrine for neonatal cardiac arrest. A previous study found that vasopressin helped newborn piglets recover with better heart and brain outcomes compared to other treatments. Research suggests that vasopressin improved survival and heart function after CPR in newborns. It might be beneficial during CPR for newborns, especially since most newborn heart problems don't respond to electric shocks. However, some studies have shown no clear advantage of vasopressin over epinephrine in general heart emergencies. While positive signs exist, more research is needed to confirm if vasopressin is more effective for newborns than the standard treatment with epinephrine. ^{2 6 7 8 9}

Who Is on the Research Team?

Georg Schmolzer

Principal Investigator

University of Alberta

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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 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 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]

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 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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S2666520424002881

Effect of vasopressin on brain and cardiac tissue during ... Vasopressin is effective in the resuscitation of asphyxiated newborn piglets and is associated with reduced inflammation of the myocardium compared to ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10372457/

Vasopressin versus epinephrine during neonatal ... Vasopressin improved post-resuscitation survival and hemodynamics, and might be an alternative cardio-resuscitative medication during neonatal CPR.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05738148

Vasopressin vs. Epinephrine During Neonatal ... Vasopressin may therefore be beneficial during neonatal CPR because in newborn infants i) asphyxia results primarily in non-shockable rhythm (asphyxia (40-45%) ...

4. nature.com nature.com/articles/s41390-023-02858-x

Comparison of various vasopressin doses to epinephrine ... Vasopressin may be an alternative to epinephrine; pediatric and adult studies reported that vasopressin is more effective during asystolic ...

5. jamanetwork.com jamanetwork.com/journals/jamainternalmedicine/fullarticle/486356

Vasopressin for Cardiac Arrest: A Systematic Review and ... Conclusions There is no clear advantage of vasopressin over epinephrine in the treatment of cardiac arrest. Guidelines for Advanced Cardiac Life Support should ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11699340/

Effect of vasopressin on brain and cardiac tissue during ... Vasopressin improves post-resuscitation survival and is associated with reduced inflammation of the myocardium compared to epinephrine. There was no evidence of ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2666520423001029

Protocol paper Vasopressin versus epinephrine during ... The current pilot trial will examine the efficacy of vasopressin versus epinephrine during CPR of asphyxiated newborn infants.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9955402/

Masked Randomized Trial of Epinephrine versus ... Vasopressin resulted in lower incidence and longer time to ROSC compared to epinephrine in a perinatal model of cardiac arrest.

9. nature.com nature.com/articles/pr201438

Vasopressin improves survival compared with epinephrine ... Vasopressin results in improved survival, lower postresuscitation troponin, and less hemodynamic compromise after CA in newborn piglets.