# Optimizing the Timing and Route of Antiarrhythmic Administration in Out-of-Hospital Cardiac Arrest

> **NIH NIH K23** · OREGON HEALTH & SCIENCE UNIVERSITY · 2024 · $191,365

## Abstract

PROJECT SUMMARY
Despite the potential for patients to make a full recovery after experiencing an out-of-hospital cardiac arrest
(OHCA) due to ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT), mortality remains near
75%. This higher mortality is partly because upwards of 50% of patients do not respond to initial defibrillation
attempts. My career goal is to become an independent, federally funded physician-scientist leading a research
program focused on improving outcomes for patients experiencing OHCA. My K23’s overall objectives are to
evaluate if earlier antiarrhythmic administration is associated with improved survival after VF/VT OHCA, how
the route of administration interacts with this association, and if changing the sequence of antiarrhythmics for
VF/VT OHCA can reduce the time to antiarrhythmic therapy in a pilot feasibility trial. My central hypothesis is
that early amiodarone administration in VF/VT OHCA can improve survival significantly compared to current
guidelines. The rationale is that current cardiac arrest care guidelines for delaying antiarrhythmic therapy until
after three shocks may reduce the efficacy of these agents, increase overall arrest duration, and reduce
survival compared to an early antiarrhythmic approach. I will complete my overall objectives through three
specific aims: (1) to assess the association between the timing and route of amiodarone administration in
VF/VT OHCA and patient survival prospectively; (2) to measure the serum amiodarone concentration of VF/VT
OHCA patients to compare the bioavailability of intraosseous routes to intravenous while accounting for time
since drug administration; and (3) to perform a pilot, stepped-wedge cluster randomized trial evaluating a
modified algorithm for VF/VT treatment to reduce the interval from arrest to amiodarone administration. These
three aims will be accomplished over five years through seamless continuation of a pilot cohort, using the
region’s highest volume cardiac arrest receiving hospital to collect serum drug concentrations, and using
existing infrastructure to conduct a pilot cluster trial. Complementing these aims are five career development
aims to facilitate training in (1) exception from informed consent randomized controlled trials; (2) population
pharmacokinetic analytic techniques; (3) causal inference and multilevel modeling; (4) adaptive clinical trial
methodology; and (5) the K-to-R transition. This proposal is significant as it focuses on improving care in the
high-mortality condition of cardiac arrest, aligning with the NHLBI strategic objectives of levering data science
and optimizing therapeutic strategies for improving health. The research is innovative because it uses a cohort
that captures novel data elements, combining this with the use of serum drug concentrations to evaluate the
efficacy of the intraosseous route to ultimately inform, in combination with pilot trial results, future studies
investigating the optim...

## Key facts

- **NIH application ID:** 10864721
- **Project number:** 1K23HL173647-01
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Joshua Lupton
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $191,365
- **Award type:** 1
- **Project period:** 2024-07-01 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10864721

## Citation

> US National Institutes of Health, RePORTER application 10864721, Optimizing the Timing and Route of Antiarrhythmic Administration in Out-of-Hospital Cardiac Arrest (1K23HL173647-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10864721. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*