VASODILATATION OR LOOP-DIURETICS FOR INITIAL TREATMENT OF PULMONARY CONGESTION DUE TO ACUTE HEART FAILURE – A RANDOMIZED PLACEBO-CONTROLLED TRIAL

The primary objective of this trial is to ascertain the most effective emergency treatment strategy for **pulmonary edema** in patients with **acute heart failure**. The trial evaluates three strategies: administration of loop-diuretics (Furosemide), vasodilation using nitrates, and a combination of both Furosemide and nitrates. The clinical relevance of this study lies in its potential to optimize acute management protocols for pulmonary congestion, thereby improving patient outcomes in a critical care setting.

Secondary objectives include increasing clinical knowledge of acute heart failure in the hyperacute setting. This objective aims to enhance understanding of the pathophysiology and treatment responses in acute heart failure, which could inform future therapeutic approaches and clinical guidelines.

The clinical trial focuses on individuals diagnosed with **acute heart failure with pulmonary congestion**. The study population includes both male and female participants aged 18 years and older. Participants are selected based on specific criteria, including the acute onset or worsening of subjective dyspnea, systolic blood pressure of at least 100 mmHg, and oxygen saturation below 94% or the need for oxygen. Clinical signs or suspicion of congestion, such as peripheral edema and rales, are also considered. The trial involves a vulnerable population, but the total number of participants is not provided by the sponsor. Lifestyle factors such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the efficacy of different emergency treatment strategies for **acute heart failure with pulmonary congestion**. This study is a randomized, placebo-controlled trial, aiming to determine the superior strategy for managing pulmonary edema within three hours of hospital admission. The trial involves three treatment arms: loop-diuretics (Furosemide), vasodilation (nitrates), and a combination of both. The primary endpoint is the number of days participants are alive and outside the hospital until day 30. Secondary endpoints include the Early Warning Score measured 6-24 hours post-intervention, therapy intensification, clinical benefit at 30 days, quality of life at 30-day follow-up, and patient-reported dyspnea assessment.

The trial is expected to run from September 2023 to December 2026. Participants will be involved in the study for a maximum treatment period of one day, with follow-up assessments extending to 30 days post-treatment. The inclusion criteria require participants to be 18 years or older, with an acute onset or worsening of dyspnea, systolic blood pressure of at least 100 mmHg, oxygen saturation below 94% or requiring oxygen, and clinical signs or suspicion of congestion. There are no specified exclusion criteria.

Study visits will include an initial screening visit to confirm eligibility based on the inclusion criteria. Following randomization, participants will receive the assigned treatment and undergo monitoring for the primary and secondary endpoints. Follow-up visits will occur at specified intervals to assess outcomes such as quality of life and clinical benefit. The end-of-study visit will conclude the participant's involvement, ensuring all data is collected and any adverse events are addressed.

Participants may be withdrawn from the study if they experience adverse reactions to the treatment, fail to comply with the study protocol, or withdraw consent. The trial is categorized as low intervention, ensuring minimal risk to participants while providing valuable data on the management of acute heart failure with pulmonary congestion.

The clinical trial involves the administration of **Isosorbide Dinitrate**, marketed under the name **Isoket**, which is utilized for its **vasodilation** properties. This experimental medication is provided in the form of a **solution for injection/infusion**. The maximum daily dose is 30 mg, with a total dose not exceeding 30 mg over a treatment period of one day. The route of administration is via injectable solution, ensuring rapid onset of action. Compliance with the dosing schedule is monitored to ensure adherence to the protocol.

Another experimental treatment in the trial is **Furosemide**, available as a 10 mg/ml solution for injection or infusion. This **loop-diuretic** is administered to manage fluid overload conditions. The maximum daily dose is set at 400 mg, with the same limit for the total dose over a one-day treatment period. The administration route is injection, and participant compliance is closely monitored to maintain the integrity of the trial data.

The trial also includes a non-experimental treatment, **Isotonisk saltvand fremstillet af sygehusapoteket**, which serves as a placebo. This inert saline solution is administered via injection, with a maximum daily and total dose of 40 ml over a one-day period. The use of this placebo allows for the assessment of the experimental treatments' efficacy by providing a baseline for comparison. Compliance with the administration of the placebo is also monitored to ensure the reliability of the trial outcomes.

Efficacy in the clinical trial titled "VASODILATATION OR LOOP-DIURETICS FOR INITIAL TREATMENT OF PULMONARY CONGESTION DUE TO ACUTE HEART FAILURE – A RANDOMIZED PLACEBO-CONTROLLED TRIAL" will be assessed using both primary and secondary endpoints. The primary endpoint is defined as the number of days alive and outside the hospital until day 30. This endpoint will provide a direct measure of the treatment's impact on patient survival and hospital discharge status.

Secondary endpoints include several parameters to evaluate the broader impact of the treatment strategies. These include the Early Warning Score measured 6-24 hours after the start of the intervention, which will help assess the immediate physiological response to treatment. Intensification of therapy, defined by the need for mechanical ventilation, renal replacement therapy, vasopressors, inotropes, or mechanical heart failure treatment, will also be monitored. Clinical benefit at 30 days will be assessed using a composite of all-cause death, intubation with mechanical ventilation, and rehospitalization, evaluated through a 'win-ratio' approach. Additionally, quality of life at the 30-day follow-up will be measured using the 5Q-DL scale, and patient-reported dyspnea will be assessed after 2-24 hours using a 7-point Likert scale.