Ignite Creation Date:
2024-05-06 @ 8:06 PM
Last Modification Date:
2024-10-26 @ 3:20 PM
Study NCT ID:
NCT06251609
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-02-09
First Post:
2024-01-19
Brief Title:
Naloxone for Opioid Associated Out of Hospital Cardiac Arrest
Sponsor:
University of California San Francisco
Organization:
University of California San Francisco
Study Overview
Official Title:
Naloxone for Opioid Associated Out of Hospital Cardiac Arrest
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
NOPACA
Brief Summary:
The investigators long-term goal is to conduct Naloxone for Opioid Associated out of Hospital Cardiac Arrest NOPACA a randomized double blind controlled trial to determine the efficacy of naloxone vs placebo in Opioid Associated out of Hospital Cardiac Arrest The investigative team plan to randomize patients in OHCA to early naloxone administration vs placebo after initial resuscitation and measure ROSC and survival Challenges to designing NOPACA include uncertainty regarding 1 the available pool of participants and number of EMS agencies needed to meet enrollment targets 2 acceptability among patients EMS and Emergency Medicine provider stakeholders and 3 estimates of the study outcomes needed for sample size estimates Toward obtaining the necessary information to design NOPACA the investigators propose a pilot RCT of participants at high risk for OA-OHCA to verify a reasonable recruitment rate treatment fidelity and acceptability and adequate retention and measurement of outcomes at follow up The investigators propose incorporating hypothesis testing of the feasibility outcomes to determine progression to a definitive trial
Detailed Description:
Rationale Opioid associated out-of-hospital cardiac arrest OA-OHCA is defined as cardiac arrest precipitated by the use of opioids with or without co-intoxicants and comorbidities In OA-OHCA hypoxia is thought reduce cardiac output resulting in hypotension bradycardia and pulseless electric activity PEA or asystole This pathophysiology is distinct from sudden cardiac death and other arrest etiologies and may benefit from targeted treatments including naloxone Naloxone is a competitive mu opioid-receptor antagonist that reverses the central nervous system respiratory and circulatory effects of opioids Naloxone improves cardiac arrest outcomes in animals and a recent retrospective analysis of cardiac arrests from 1300 EMS agencies found that survival and return of spontaneous circulation ROSC were higher in those given naloxone compared to those not receiving naloxone in patients presenting in PEA Whether naloxone benefits patients in OA-OHCA is a knowledge gap that should be assessed in a randomized controlled trial
The long-term goal is to conduct Naloxone for Opioid Associated Out of Hospital Cardiac Arrest NOPACA a randomized controlled trial to determine the efficacy of naloxone vs placebo in OA-OHCA To design NOPACA the investigators propose a pilot RCT of participants at high risk for OA-OHCA to verify a reasonable recruitment rate treatment fidelity and adequate retention and measurement of outcomes at follow up
Hypothesis The overall hypothesis is that early EMS administration of naloxone in addition to standard resuscitation improves survival in patients in OA-OHCA The hypothesis of the pilot RCT is that the investigators can feasibly enroll randomize administer naloxone and measure ROSC and survival at hospital discharge
Aim 1 Determine the ability to enroll and randomize participants into a RCT of naloxone vs placebo for OA-OHCA
Aim 2 Determine the ability to deliver the treatments per protocol after standard initial resuscitation measures within 5 minutes of initiating CPR and giving the first dose of epinephrine
Aim 3 Determine the ability to measure primary efficacy outcomes rate of ROSC at ED arrival and survival at hospital discharge23 and obtain a preliminary estimate of effect size for the future trial
Design Pilot randomized parallel group placebo-controlled trial Study population Participants are adults in EMS attended out of hospital cardiac arrest in whom EMS has initiated ACLS treatment including ventilation CPR and obtain IVIO access and administered epinephrine Based on prior research to identify patients at high risk of OA-OHCA participants meeting less than 60 years old who receive initial resuscitation measures will be eligible for inclusion
Setting The University of California San Francisco and San Francisco Fire Department Fire Department
Intervention Naloxone 2mg 2ml of 1mgml solution administered by EMS personnel via the IV or IO route immediately within 5 minutes following the first dose of epinephrine
Control Saline 2ml will be supplied in pre-filled syringes within numbered trial treatment packs
Feasibility outcomes will allow the investigators to determine whether the NOPACA future trial is feasible and estimate how many sites might be needed
Number of EMS treated OHCA patients who meet inclusion criteria per month with a goal of 3 per month
Proportion of those randomized participants who receive the study drug based on randomization assignment with a target treatment fidelity 75
Proportion of randomized participants who are retained in the study with a goal of retention and ascertainment of outcomes in 75 of participants
Efficacy outcomes include sustained ROSC survival to hospital discharge and neurologic outcome will be assessed with the modified Rankin Scale
Statistical analyses and reporting will adhere to CONSORT guidelines The two groups will be compared in relation to baseline patient and cardiac arrest characteristics using descriptive statistics All analyses of outcomes will be conducted on an intention-to-treat basis including patients randomized to a study arm and meeting all inclusion criteria and no known exclusion criteria at the time of drug administration Point and confidence estimates will be the preferred measure to report group differences and all confidence intervals will have 95 coverage All tests will be two-sided and a p-value 005 will be considered significant Significance By conducting Pilot-NOPACA the investigators will determine whether the plan for NOPACA a definitive trial of naloxone for OA-OHCA is feasible Also the investigators will have obtained the regulatory approvals including Exception from Informed Consent Determining the benefit of naloxone in OA-OHCA is an American Heart Association research priority and may save thousands of lives each year in a worsening opioid epidemic
The long-term goal is to conduct Naloxone for Opioid Associated Out of Hospital Cardiac Arrest NOPACA a randomized controlled trial to determine the efficacy of naloxone vs placebo in OA-OHCA To design NOPACA the investigators propose a pilot RCT of participants at high risk for OA-OHCA to verify a reasonable recruitment rate treatment fidelity and adequate retention and measurement of outcomes at follow up
Hypothesis The overall hypothesis is that early EMS administration of naloxone in addition to standard resuscitation improves survival in patients in OA-OHCA The hypothesis of the pilot RCT is that the investigators can feasibly enroll randomize administer naloxone and measure ROSC and survival at hospital discharge
Aim 1 Determine the ability to enroll and randomize participants into a RCT of naloxone vs placebo for OA-OHCA
Aim 2 Determine the ability to deliver the treatments per protocol after standard initial resuscitation measures within 5 minutes of initiating CPR and giving the first dose of epinephrine
Aim 3 Determine the ability to measure primary efficacy outcomes rate of ROSC at ED arrival and survival at hospital discharge23 and obtain a preliminary estimate of effect size for the future trial
Design Pilot randomized parallel group placebo-controlled trial Study population Participants are adults in EMS attended out of hospital cardiac arrest in whom EMS has initiated ACLS treatment including ventilation CPR and obtain IVIO access and administered epinephrine Based on prior research to identify patients at high risk of OA-OHCA participants meeting less than 60 years old who receive initial resuscitation measures will be eligible for inclusion
Setting The University of California San Francisco and San Francisco Fire Department Fire Department
Intervention Naloxone 2mg 2ml of 1mgml solution administered by EMS personnel via the IV or IO route immediately within 5 minutes following the first dose of epinephrine
Control Saline 2ml will be supplied in pre-filled syringes within numbered trial treatment packs
Feasibility outcomes will allow the investigators to determine whether the NOPACA future trial is feasible and estimate how many sites might be needed
Number of EMS treated OHCA patients who meet inclusion criteria per month with a goal of 3 per month
Proportion of those randomized participants who receive the study drug based on randomization assignment with a target treatment fidelity 75
Proportion of randomized participants who are retained in the study with a goal of retention and ascertainment of outcomes in 75 of participants
Efficacy outcomes include sustained ROSC survival to hospital discharge and neurologic outcome will be assessed with the modified Rankin Scale
Statistical analyses and reporting will adhere to CONSORT guidelines The two groups will be compared in relation to baseline patient and cardiac arrest characteristics using descriptive statistics All analyses of outcomes will be conducted on an intention-to-treat basis including patients randomized to a study arm and meeting all inclusion criteria and no known exclusion criteria at the time of drug administration Point and confidence estimates will be the preferred measure to report group differences and all confidence intervals will have 95 coverage All tests will be two-sided and a p-value 005 will be considered significant Significance By conducting Pilot-NOPACA the investigators will determine whether the plan for NOPACA a definitive trial of naloxone for OA-OHCA is feasible Also the investigators will have obtained the regulatory approvals including Exception from Informed Consent Determining the benefit of naloxone in OA-OHCA is an American Heart Association research priority and may save thousands of lives each year in a worsening opioid epidemic
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None