Intravenous vs. Intraosseous Vascular Access During Out-of-Hospital Cardiac Arrest – A Randomized Clinical Trial

The primary objective of this randomized clinical trial is to evaluate whether there is a difference in the **return of spontaneous circulation** based on the type of vascular access, either intravenous or intraosseous, used during an out-of-hospital cardiac arrest (OHCA). This is clinically relevant as the return of spontaneous circulation is a critical determinant of survival and neurological outcomes in patients experiencing OHCA.

Secondary objectives include determining whether there is a difference in survival at 30 days and/or survival at 30 days with a favorable neurological outcome, as measured by the modified Rankin Scale (mRS 0-3), depending on the type of vascular access used during OHCA. These outcomes are important for assessing the long-term benefits and potential neurological recovery associated with different vascular access methods in emergency settings.

The clinical trial focuses on individuals experiencing **out-of-hospital cardiac arrest (OHCA)**, with the primary objective of assessing the impact of different types of vascular access on the return of spontaneous circulation. The study population includes both male and female participants aged 18 years and older. Participants are selected based on the occurrence of OHCA and the need for either intravenous or intraosseous vascular access during the cardiac arrest event. The trial does not specifically target a vulnerable population, and no additional lifestyle considerations such as diet or physical activity are specified. The sponsor has not provided information regarding the total number of participants involved in the study.

The clinical trial is designed to evaluate the efficacy of different types of vascular access during **out-of-hospital cardiac arrest** (OHCA). This is a **randomized**, **controlled**, and **double-blind** study, conducted in Phase 4, to determine whether there is a difference in the return of spontaneous circulation (ROSC) based on the type of vascular access, either intravenous or intraosseous, used during OHCA. The trial is expected to run from May 18, 2022, to March 1, 2024, with the primary endpoint being sustained ROSC, defined as palpable pulses or other signs of circulation without the need for chest compressions for more than 20 minutes. Secondary endpoints include survival and neurological outcomes at 30 days, assessed using the modified Rankin Scale (mRS).

Participants will be screened based on the inclusion criteria, which require individuals to be 18 years or older, experiencing OHCA, and having an indication for intravenous or intraosseous vascular access during cardiac arrest. There are no specified exclusion criteria. The study involves several visits, starting with an inclusion (screening) visit to confirm eligibility. Follow-up visits will be conducted to monitor the primary and secondary endpoints, with the final visit marking the end of the study. The expected length of participant involvement is approximately 30 days, with conditions for early termination including withdrawal of consent or any adverse events that may compromise participant safety.

The trial involves the administration of **epinephrine** and **amiodarone** via intravenous bolus use, with maximum daily doses of 15 mg and 450 mg, respectively. The maximum treatment period for each participant is one day. The study is not classified as low intervention, and the trial category is justified as a Phase II trial in adult subjects. Participants' involvement may be terminated early if they experience significant adverse effects or if they choose to withdraw from the study. The trial aims to provide valuable insights into the optimal vascular access method during OHCA, potentially influencing future clinical practices and guidelines.

The clinical trial involves the administration of **EPINEPHRINE**, also known as **adrenaline tartrate ph. eur.**, as an experimental medication. The pharmaceutical form of this medication is denoted as PHF00231MIG. The administration route is via **intravenous bolus use**. The maximum daily dose is 15 mg, with a total maximum dose of 15 mg over the treatment period, which is limited to one day. The medication is not formulated for pediatric use. The trial does not involve any orphan drug designation for this product. Compliance with the dosing schedule is monitored according to the study protocol.

Another experimental medication used in the trial is **AMIODARONE**, with the pharmaceutical form identified as PHF00245MIG. Similar to epinephrine, amiodarone is administered through **intravenous bolus use**. The maximum daily dose for amiodarone is 450 mg, with a total maximum dose of 450 mg over a one-day treatment period. This medication is also not formulated for pediatric use and does not have an orphan drug designation. Participant compliance with the dosing regimen is ensured through adherence to the study protocol.

Both medications are administered as part of a randomized clinical trial aimed at evaluating the effectiveness of different vascular access methods during out-of-hospital cardiac arrest. The trial does not include any non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments. All relevant information regarding drug administration and dosing schedules is detailed in the study protocol, and participant compliance is closely monitored throughout the trial.

Efficacy in this clinical trial will be assessed by evaluating the primary and secondary endpoints. The primary endpoint is the **sustained return of spontaneous circulation (ROSC)**, defined as the presence of palpable pulses or other signs of circulation without the need for chest compressions, sustained for more than 20 minutes. This endpoint will be used to determine the effectiveness of intravenous versus intraosseous vascular access during out-of-hospital cardiac arrest.

Secondary endpoints include survival and neurological outcomes at 30 days. Neurological outcomes will be measured using the modified Rankin Scale (mRS), with scores ranging from 0 to 6. These scores will be presented as counts and percentages and will be dichotomized into favorable (mRS 0-3) and unfavorable (mRS 4-6) outcomes. The assessment of these endpoints will provide additional insights into the efficacy of the interventions being tested in the trial.