Evaluation of Recombinant Coagulation Factor VIIa (Eptacog Alfa, Activated) for Acute Hemorrhagic Stroke in Early Administration: A Randomized Controlled Trial

The primary objective of the FASTEST trial is to determine the efficacy of **recombinant Factor VIIa (rFVIIa)** in improving functional outcomes for patients experiencing acute spontaneous intracerebral hemorrhage (ICH) when administered within 2 hours of onset. This is assessed using the modified Rankin Scale (mRS) at 180 days, which measures the degree of disability or dependence in daily activities. Establishing an effective treatment within this critical time window is clinically significant as it could potentially reduce long-term disability in patients with acute hemorrhagic stroke.

The secondary objective is to evaluate whether treatment with rFVIIa within 2 hours of ICH onset reduces bleeding, as observed in routine head imaging at 24 hours post-treatment, compared to placebo. This objective aims to assess the potential of rFVIIa to limit hemorrhagic progression, which is crucial for improving patient outcomes and reducing complications associated with acute hemorrhagic stroke.

The clinical trial involves a total of **1216 participants** who are being studied to evaluate the efficacy of a treatment for **acute haemorrhagic stroke**, specifically intracerebral hemorrhage (ICH). The study population includes both male and female subjects, aged between **18 and 80 years**, who have experienced spontaneous ICH. Participants were selected based on their ability to receive the study medication, either recombinant Factor VIIa (rFVIIa) or placebo, within **120 minutes** of stroke onset or the last known well time. The trial includes a vulnerable population, adhering to specific informed consent guidelines applicable in various countries. Participants' general health status is not specified, but they are required to meet the inclusion criteria related to the timing of treatment administration. Lifestyle considerations such as diet, physical activity, or habits are not detailed in the available data.

The clinical trial is designed as a **randomized, double-blind, placebo-controlled** study to evaluate the efficacy and safety of **recombinant Factor VIIa (rFVIIa)** in treating **acute hemorrhagic stroke**. The trial aims to determine if administering rFVIIa within two hours of stroke onset improves functional outcomes compared to a placebo. The study will involve participants aged 18 to 80 years who have experienced a spontaneous intracerebral hemorrhage (ICH) and can receive the study medication within 120 minutes of stroke onset. The trial is expected to run from December 2021 to June 2026, with the primary outcome measured by the modified Rankin Scale (mRS) at 180 days post-treatment.

Participants will undergo a series of study visits, beginning with a screening visit to confirm eligibility based on inclusion criteria, such as age and the ability to administer treatment within the specified time frame. Following the initial treatment, participants will have follow-up visits at 90 days and 180 days to assess secondary endpoints, including changes in ICH volume and functional outcomes using the mRS and EQ-5D. The end-of-study visit will occur at 180 days, where the primary outcome will be evaluated.

The expected length of participant involvement is approximately six months, from the initial treatment to the final assessment. Conditions that may lead to early termination from the study include the inability to adhere to the study protocol, withdrawal of consent, or any adverse events that compromise participant safety. The trial will adhere to ethical guidelines, including obtaining informed consent per country-specific regulations. The study medication will be administered as an **intravenous slow bolus injection**, with a maximum daily dose of 80 µg/kg.

The clinical trial involves the administration of **NovoSeven**, a recombinant Factor VIIa (rFVIIa), with the active substance **eptacog alfa (activated)**. This experimental medication is provided in the form of a **powder and solvent for solution for injection**. The pharmaceutical form is a **solution for injection**, and it is administered via **intravenous slow bolus injection**. The dosage is calculated based on the participant's body weight, with a maximum daily dose of 80 µg/kg. The treatment is administered within a maximum period of one day. The medication is manufactured by Novo Nordisk A/S and is identified by the marketing authorization number EU/1/96/006/010. Compliance with the dosing schedule is monitored to ensure adherence to the protocol.

The study also includes a **placebo** group, which receives an **Eptacog alfa Placebo**. The placebo is used as a comparator treatment to evaluate the efficacy of the experimental medication. The placebo does not contain any active substance and is administered in a manner consistent with the experimental treatment to maintain blinding within the trial. The placebo is not associated with any specific pharmaceutical form or route of administration, as it serves solely as a control measure in the study.

The efficacy of the treatment in the FASTEST trial will be assessed using the **modified Rankin Scale (mRS)**, a commonly used scale for measuring the degree of disability or dependence in daily activities. The primary endpoint is the distribution of the ordinal mRS at 180 days, categorized into scores of 0-2, 3, and 4-6. Secondary endpoints include the full range of the ordinal mRS, utility-weighted Rankin Score, mRS of 0-2, and EQ-5D at both 90 days and 180 days. Additionally, changes in the volume of intracerebral hemorrhage (ICH) and intraventricular hemorrhage (ICH-IVH) will be evaluated between the baseline routine CT and the 24-hour routine CT.