Evaluation of Intra-Abdominal Pressure and Ultrasound-Guided Diuretic Therapy with Furosemide and Hydrochlorothiazide in Acute Heart Failure Patients

The primary objective of this study is to evaluate the complete resolution of **congestion** using the ADVOR scale after the first 72 hours of intravenous diuretic treatment in patients with **acute heart failure**. This assessment is conducted between a standard treatment group and an intervention group utilizing intra-abdominal pressure and ultrasound. The clinical relevance of this objective lies in its potential to optimize decongestive therapy, thereby improving patient outcomes and reducing hospital stay duration.

Secondary objectives include:

• Evaluating the complete resolution of pulmonary congestion by ultrasound (lines B) after 72 hours of treatment.
• Assessing the significant reduction in intravascular congestion using inferior vena cava diameter and VExUS protocol.
• Evaluating the diuretic response, defined as the total diuresis volume per total dose of furosemide administered.
• Comparing the days and doses of intravenous loop diuretics and hydrochlorothiazide used during the initial 72 hours of hospital admission.
• Analyzing differences in the worsening of heart failure, defined by the need for intravenous loop diuretics post-discharge at 30 and 90 days.
• Comparing the incidence of cardiovascular death at 30 and 90 days post-hospitalization.
• Analyzing whether the intervention strategy reduces the mean hospital stay.
• Evaluating the proportion of patients prescribed guideline-directed medical therapy at discharge and at 30-90 days.
• Assessing whether the intervention strategy is associated with a lower percentage of renal function deterioration, defined as an increase in creatinine levels.
• Analyzing the association of the intervention strategy with a lower percentage of ionic alterations related to intravenous diuretics, such as hyponatremia, hypokalemia, or hyperkalemia.

The clinical trial focuses on individuals diagnosed with **Acute Heart Failure**. The study population includes both men and women over the age of 18, as per the latest heart failure guidelines published in 2022. Participants are required to have an NT-proBNP level greater than 1000 pg/mL or a BNP level greater than 250 pg/mL. The trial does not involve a vulnerable population. Participants must undergo bladder catheterization for intra-abdominal pressure measurement and exhibit an intravascular or mixed pattern of congestion, characterized by clinical signs such as edema, ascites, or pleural effusion. The sponsor has not provided information regarding the total number of participants. The trial population was selected based on these criteria, and all participants must provide informed consent. 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 diuretic treatment in patients with **acute heart failure** using intra-abdominal pressure and clinical ultrasound as guiding tools. This study is a randomized, double-blind, controlled trial with an estimated duration from September 2024 to September 2026. Participants will be randomly assigned to either the standard treatment group or the intervention group, which utilizes intra-abdominal pressure and ultrasound for treatment guidance. The primary objective is to assess the complete resolution of congestion within the first 72 hours of intravenous diuretic treatment, as measured by the ADVOR scale.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, diagnosis of heart failure, and specific biomarker levels. Following successful screening, participants will be enrolled in the trial and receive either **furosemide** or **hydrochlorothiazide** as part of their decongestive therapy. The trial includes follow-up visits to monitor treatment efficacy and safety, with the primary endpoint being the absence of congestion after 72 hours of treatment. The end-of-study visit will occur at the conclusion of the treatment period, which may last up to 12 weeks depending on the assigned treatment regimen.

The expected length of participant involvement is up to 12 weeks, with conditions for early termination including adverse events, withdrawal of consent, or non-compliance with study protocols. The trial is categorized as low interventional, as the investigational medicinal products are used according to their marketing authorizations and at authorized doses. This study aims to provide valuable insights into optimizing diuretic therapy for patients with acute heart failure, potentially improving clinical outcomes through tailored treatment strategies.

The clinical trial involves the administration of **furosemide** in two pharmaceutical forms: a solution for injection and a tablet. The **furosemide** solution for injection is administered via **intravenous administration**. The maximum daily dose for this form is 250 mg, with a total maximum dose of 3500 mg over a treatment period of up to 2 days. This form is utilized as part of the decongestive therapy regimen in the study. The **furosemide** tablet is administered orally, with a maximum daily dose of 160 mg and a total maximum dose of 13440 mg over a treatment period of up to 12 days. This oral form is also part of the decongestive therapy used in the trial.

Additionally, the study includes the use of **hydrochlorothiazide** in tablet form, administered orally. The maximum daily dose for **hydrochlorothiazide** is 100 mg, with a total maximum dose of 8400 mg over a treatment period of up to 12 days. This medication is also part of the decongestive therapy regimen. All active substances in the trial, including **furosemide** and **hydrochlorothiazide**, are of chemical origin. Participant compliance with the dosing schedules is monitored throughout the study to ensure adherence to the treatment protocol.

Efficacy in this clinical trial will be assessed by evaluating the complete resolution of congestion in patients with acute heart failure. The primary endpoint for efficacy is the absence of congestion after the first 72 hours of intravenous diuretic treatment during hospitalization, as determined by the ADVOR scale. This scale will be used to measure the resolution of congestion, providing a standardized method for assessment.

The trial will compare the standard treatment group with an intervention group that utilizes intra-abdominal pressure and clinical ultrasound to guide diuretic treatment. The efficacy assessment will focus on the initial 72-hour period following the administration of intravenous diuretics, specifically **furosemide** and **hydrochlorothiazide**, which are administered either intravenously or orally as part of decongestive therapy. The trial aims to determine the effectiveness of these treatments in achieving the primary endpoint of congestion resolution.