Naloxone for Opioid Overdose and Cardiac Arrest

(NOPACA Trial)

Overseen By Ralph C. Wang, MD, MAS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of California, San Francisco

Must not be taking: Naloxone

Disqualifiers: Trauma, Choking, Drowning, Pregnancy, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: Immediate (within 5 minutes of CPR initiation)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether naloxone, a medication for opioid overdoses, can aid survival in cardiac arrest linked to opioid use. Researchers will compare naloxone's effects to a placebo (a harmless saltwater solution) to determine which is more effective after emergency medical services begin resuscitation. The trial seeks adults who have experienced cardiac arrest outside a hospital and are at risk due to opioid use, as identified by emergency responders. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group, giving participants an opportunity to contribute to potentially life-saving advancements.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

Is there any evidence suggesting that naloxone is likely to be safe for humans?

Research shows that naloxone is generally safe and effectively reverses opioid overdoses. Studies have found that when a drug overdose causes the heart to stop, naloxone can significantly increase survival chances and help restart the heart. The FDA has approved naloxone for treating opioid overdoses, confirming its safety for this use. No major side effects are commonly associated with naloxone, making it reliable in emergencies. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about naloxone for opioid overdose and cardiac arrest because it offers a potentially life-saving intervention administered rapidly in critical situations. Unlike most treatments that mainly focus on reversing opioid effects, naloxone is being tested for its ability to be administered immediately after the first dose of epinephrine during cardiac arrest, potentially enhancing outcomes. This approach is unique because it explores a new timing and combination strategy with epinephrine, aiming to improve survival rates in these emergencies.

What evidence suggests that naloxone might be an effective treatment for opioid overdose and cardiac arrest?

Research has shown that naloxone, which participants in this trial may receive, can greatly improve outcomes in cases of opioid-related cardiac arrest. One study found that naloxone more than doubled the chances of patients regaining their pulse and surviving until hospital discharge. Another study reported that 15.9% of patients who received naloxone survived to leave the hospital, compared to only 9.7% of those who did not receive it. These findings suggest that naloxone might increase survival rates in opioid overdose situations, making it a promising treatment during opioid-related cardiac arrest. ^{1 2 6 7 8}

Who Is on the Research Team?

Ralph Wang, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for individuals who have experienced an out-of-hospital cardiac arrest suspected to be due to opioid overdose. Specific details about eligibility criteria are not provided, but typically participants would need to meet certain health conditions and agree to the study's procedures.

Inclusion Criteria

I received advanced life support from EMS for an out-of-hospital cardiac arrest.

I've received CPR, ventilation, and an initial dose of epinephrine.

I am under 50 and had a sudden, unexpected collapse.

Exclusion Criteria

I will receive or have received naloxone from emergency services.

Known or apparent pregnancy

Prior inclusion in the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive naloxone or placebo administered by EMS personnel immediately following the first dose of epinephrine

Immediate (within 5 minutes of CPR initiation)

1 visit (EMS encounter)

Follow-up

Participants are monitored for survival to hospital discharge and sustained ROSC

Up to 5 days

Hospital monitoring

Outcome Assessment

Assessment of primary and secondary outcomes including survival to hospital discharge and neurologic outcome

Through hospital discharge

What Are the Treatments Tested in This Trial?

Interventions

• Naloxone

Trial Overview

The NOPACA trial is testing whether naloxone (a medication that can reverse the effects of opioids) is more effective than a placebo (saline solution) in improving outcomes after cardiac arrest outside of hospital settings. Participants will be randomly assigned to receive either naloxone or placebo.

How Is the Trial Designed?

Group I: Naloxone Active Control 1 Intervention

The intervention consists of naloxone 2mg (2ml of 1mg/ml solution) administered by EMS personnel via the IV or IO route. The study intervention will be administered immediately (within 5 minutes) following the first dose of epinephrine.

Group II: Saline Placebo Group 1 Intervention

Saline 2ml will be supplied in pre-filled syringes within numbered trial treatment packs. The trial will be double-blind; patients, investigators, and the clinical team will be blinded. Only the pharmacy providing the numbered syringes will be aware of the allocation but will not be involved with clinical care or outcome evaluation. The saline placebo will be stored in syringes identical to the naloxone syringes without identifying features.

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

Approved in United States as Naloxone for:

• Opioid overdose reversal

Approved in European Union as Naloxone for:

• Opioid overdose reversal

Approved in Canada as Naloxone for:

• Opioid overdose reversal

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Published Research Related to This Trial

Buprenorphine/naloxone has a unique pharmacology that provides a ceiling effect on its cardio-respiratory depressant properties, making it potentially safer than other opioids, especially at higher doses.

Data from various safety monitoring systems indicate that buprenorphine/naloxone has a favorable safety profile compared to other opioids and psychotropic drugs, suggesting it may reduce the risk of overdose-related morbidity and mortality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Question About the Safety of Buprenorphine/Naloxone and Benzodiazepine Drugs. Howland, RH.[2015]

Naloxone is a safe and effective antidote for opioid overdose, with a long history of use by healthcare professionals, and expanding access to it for high-risk individuals and their families is a key public health initiative.

While naloxone is generally safe, its administration can lead to varying levels of adverse reactions, especially with higher doses or intravenous use, highlighting the importance of training for non-healthcare professionals in recognizing overdoses and administering naloxone correctly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of naloxone safety for opioid overdose: practical considerations for new technology and expanded public access. Wermeling, DP.[2020]

In a study involving 42 healthy participants, the naloxone auto-injector (NAI) was significantly more effective than the intranasal delivery system (NXN) for administering naloxone during a simulated opioid overdose, with 90.5% success for NAI compared to 0% for NXN before training.

After training, 100% of participants successfully used NAI, while only 57.1% could use NXN, highlighting that NAI is easier to use and requires less training for effective administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Usability Study of a Novel Auto-Injector and an Intranasal System for Naloxone Delivery. Edwards, ET., Edwards, ES., Davis, E., et al.[2020]

The naloxone auto-injector (EZVIO™), approved by the FDA in 2014, is designed for easy use by anyone, including laypersons, to rapidly administer naloxone during an opioid overdose, potentially saving lives.

This device is safe and portable, requiring minimal instruction for use, and should be made widely available to individuals who may encounter opioid users, emphasizing the importance of quick response in overdose situations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of the safety and ease of use of the naloxone auto-injector for the reversal of opioid overdose. Merlin, MA., Ariyaprakai, N., Arshad, FH.[2020]

Intranasal naloxone is considered the best option for opioid reversal in prehospital settings due to its balance of cost, effectiveness, and safety for the administrator, based on an analysis of 8 studies.

There is no clear consensus on the best route of naloxone administration, as various methods (intramuscular, intranasal, intravenous, and subcutaneous) were evaluated but showed differing results in terms of administration time and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naloxone Administration for Opioid Overdose Reversal in the Prehospital Setting: Implications for Pharmacists. Weaver, L., Palombi, L., Bastianelli, KMS.[2018]

Heroin overdoses have become more common, with risk factors including recent abstinence and polydrug use, highlighting the urgent need for effective prevention strategies.

Naloxone is a safe and effective treatment for reversing heroin overdose effects, as it quickly counteracts respiratory depression and sedation, making it a crucial tool for overdose prevention in communities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prescription naloxone: a novel approach to heroin overdose prevention. Sporer, KA., Kral, AH.[2022]

The sustained release naltrexone implant significantly reduced opioid overdoses in a cohort of 361 heroin-dependent individuals, with no overdoses reported in the 6 months following treatment, compared to 21 overdoses in the 6 months prior.

While the implant effectively prevented opioid overdoses, there was an increase in sedative overdoses shortly after treatment, highlighting the need for comprehensive management of poly-substance use among heroin users.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reducing hospital presentations for opioid overdose in patients treated with sustained release naltrexone implants. Hulse, GK., Tait, RJ., Comer, SD., et al.[2018]

Current opioid overdose treatment relies on naloxone, which has limitations, especially in mass casualty situations involving synthetic opioids, prompting the need for new alternatives.

Emerging treatments discussed at a 2019 scientific meeting include intranasal nalmefene, which has a longer action than naloxone, and novel strategies like covalent naloxone nanoparticles and detoxifying nanosponge decoy receptors, which could enhance the effectiveness of opioid overdose interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Countermeasures for Preventing and Treating Opioid Overdose. France, CP., Ahern, GP., Averick, S., et al.[2021]

In a study of 89 emergency department patients who experienced accidental opioid overdoses, 70% reported a history of previous overdoses, highlighting the ongoing crisis of opioid misuse.

Despite the availability of naloxone kits, only 31% of participants had access to one, and most who did reported no change in their opioid use patterns after obtaining naloxone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naloxone Use Among Emergency Department Patients with Opioid Overdose. Marco, CA., Trautman, W., Cook, A., et al.[2018]

Citations

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In the naloxone group, 185 of 1165 patients (15.9%) survived to hospital discharge, while in the nonexposed group, 682 of 7030 (9.7%) survived ...

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“Surprisingly, our findings showed that naloxone was associated with improved clinical outcomes in both drug-related cardiac arrests and non- ...

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OHCA patients who received naloxone, despite being younger and having fewer comorbidities, had similar outcomes compared to those who received usual care.

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health.ucdavis.edu/patients-visitors/news/headlines/can-naloxone-improve-survival-rates-of-patients-with-cardiac-arrest/2024/08

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Naloxone Hydrochloride

All approved naloxone products are considered safe and effective for reversal of opioid overdose. • Nominal dosage does not directly ...

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sciencedirect.com

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A chain of survival for drug overdose

Naloxone is beneficial prior to cardiac arrest, and of uncertain benefit during cardiac arrest. If naloxone has already been administered and the patient is not ...