Clinical Research Directory

Optimal Diuretic Therapies for Acute Heart Failure With Volume Overload

This trial aims to identify the best strategy for treating acute heart failure (AHF) with volume overload in patients at risk of diuretic resistance. It is a double-blinded, randomized, controlled, multicenter study comparing loop-diuretics combined with metolazone, loop-diuretics combined with acetazolamide, and loop-diuretics with matching placebos. Eligible participants are adults aged 18 years or older who are hospitalized with AHF and have clinical signs of congestion and a risk of diuretic resistance. The primary outcome is the number of days alive and out of hospital through day 30. Secondary outcomes are clinical benefit at 30 days, assessed using a hierarchical win ratio; days alive and out of hospital through day 90; and the duration of the index hospital admission. The trial aims to enroll 939 participants across three treatment arms (313 per arm). The sample size is based on detecting a clinically relevant between-group difference of two days alive and out of hospital through day 30, with 80% power and adjustment for comparisons between the three groups.

Assessing the Clinical Outcomes of Dapagliflozin Versus Acetazolamide in Patients With Acute Heart Failure

This study investigates the comparative clinical outcomes of dapagliflozin, an SGLT-2 inhibitor, versus acetazolamide, a carbonic anhydrase inhibitor, in patients hospitalized with acute heart failure (AHF). The trial aims to assess the effectiveness of these drugs in improving natriuretic and diuretic responses and shortening hospital stays. Dapagliflozin and acetazolamide will be added to standard loop diuretic therapy, and their safety profiles will be evaluated to identify potential side effects. This research seeks to provide evidence for incorporating these drugs into AHF management, with the potential to improve clinical outcomes.

Oxygen Targets in Acute Heart Failure With Pulmonary Congestion

REDOX-AHF compared two oxygen saturation targets in adults admitted with acute heart failure and clinical or radiological signs of congestion. Participants were randomly assigned to a restrictive target of 89-91% or a liberal target of 95-97% for 24 hours. An automated oxygen delivery device adjusted oxygen flow while concealing the assigned target from participants and study staff. The main assessment was lung fluid content after 24 hours, measured noninvasively by remote dielectric sensing (ReDS). The trial was conducted at two Danish hospitals. A total of 135 participants were randomized; 134 remained in the modified intention-to-treat population after one participant withdrew consent. The target of 122 participants with complete primary-outcome measurements was reached. Follow-up continued to day 30.

DECONGEST-AHF: Vasodilatation or Loop Diuretics in Acute Heart Failure

DECONGEST-AHF compares three initial treatments for adults admitted with suspected pulmonary congestion due to acute heart failure: intravenous furosemide, intravenous isosorbide dinitrate, or both medicines together. The aim is to determine which treatment gives patients the most days alive and outside hospital during the first 30 days. The trial is investigator-initiated, multicentre, randomised and blinded, with 1,041 participants allocated equally to three groups. During the first six hours, participants receive repeated boluses of 40 mg furosemide with nitrate placebo, 3 mg isosorbide dinitrate with furosemide placebo, or both active medicines. Doses are repeated at the treating physician's discretion within the protocol limits. Other usual care continues, and treatment may be stopped early if clinically required. An embedded substudy will examine early clinical and haemodynamic responses in 79 participants from the main trial, using repeated bedside measurements during the first 360 minutes. The main trial treatment groups and primary outcome are unchanged.

Digoxin Short Term Treatment Assessment Randomized Trial in AHF

AHFS management is challenging and most of the used drugs has failed to decrease post-discharge mortality and readmission rates which represent the most important goal in AHFS. Digoxin processes many characteristics of a beneficial drug for heart failure, however recent publications has rose concerns about its safety profile and therefore decreasing its use. Whether digoxin is efficient and safe in short term treatment of acute heart failure is a question that should be studied.

Pharmacological Optimization in Prevention in Heart Failure: A Sex-gap?

The goal of this clinical trial is to learn whether a rapid and intensive optimization of heart failure medications in women can improve outcomes after hospitalization for heart failure. It will also investigate the safety and the tolerance of these treatments when given at full guideline-recommended doses. The main questions it aims to answer are: 1. Does intensive medication optimization reduce death or hospital readmissions for heart failure within one year? 2. Do women benefit as much as men from intensive and full-dose heart failure therapy? 3. Is this treatment protocol safe and feasible also in women? Researchers will compare two groups of women hospitalized for heart failure: * High-intensity care: starting and increasing all recommended heart-failure medications as quickly as possible and monitoring patients closely during the first weeks after discharge. * Usual care: medications are started and adjusted gradually, according to the judgment of the treating cardiologist and the patient's usual care team. The study will follow participants for 12 months to see whether the high-intensity strategy reduces death, hospital readmission for heart failure, or worsening symptoms. It will also evaluate side effects, medication tolerance, and quality of life. Participants will be randomly assigned to one of the two groups, attend regular follow-up visits for one year, complete a short quality-of-life questionnaire (EQ-5D). This study will include about 360 women from 13 hospitals in Italy. It is sponsored by IRCCS Policlinico San Donato and funded by the Italian Medicines Agency (AIFA).

Heart Failure-USB: Prediction and Progression

This retrospective cohort study is to identify triggers of heart failure (HF) development and drivers of HF progression as well as the underlying cardiac disease (phenotype) to identify patients at risk and predict the clinical course of the disease. Data of patients who were hospitalized during the years 2010-2023 with acute coronary syndrome (ACS) and/ or with acute heart failure (AHF) will be collected and analyzed. In a subgroup cohort efficacy and safety of digoxin in patients with acute heart failure triggered by tachyarrhythmia will be evaluated.

Randomized Controlled Trial of urinE chemiStry Guided aCute heArt faiLure treATmEnt (ESCALATE)

This is a randomized trial of protocolized diuretic therapy guided by urinary sodium compared to structured usual care in ED patients with AHF. Participants will be recruited following an initial standard evaluation in the ED and randomized in a 1:1 fashion to structured usual care or protocolized diuretic therapy guided by urinary sodium.

Cardiac Assessment and Takotsubo-stunning Among COPD-exacerbations In-Hospital

The goal of this prospective observational study is to investigate to what extent acute exacerbation of chronic obstructive pulmonary disease (AE-COPD) triggers Takotsubo-stunning, and how this affects the outcome for these patients. The main questions it aims to answer are: 1. What is cumulative incidence of Takotsubo-stunning in patients hospitalized for AE-COPD at Sahlgrenska University Hospital/S (Gothenburg, Sweden)? 2. Among patients hospitalized for AE-COPD at Sahlgrenska University Hospital/S, what is the risk of in-hospital clinical manifestations of acute heart failure in patients with Takotsubo-stunning compared to those without?

Diuretic Treatment in Acute Heart Failure With Volume Overload Guided by Serial Spot Urine Sodium Assessment

This is a pragmatic, multicenter, interventional, parallel-arm, randomized, open-label trial to investigate whether a diuretic regimen, based on serial assessment of sodium concentration (UNa) on spot urine samples after diuretic administration and with low-threshold use of combination diuretic therapy, improves decongestion versus usual care in acute heart failure (AHF), potentially leading to better clinical outcomes.

A Study to Determine the Efficacy and Safety of Finerenone on Morbidity and Mortality Among Hospitalized Heart Failure Patients

Finerenone will be compared to placebo to determine efficacy and safety of treatment in patients hospitalized with acute decompensated heart failure (HF) and mildly reduced or preserved left ventricular ejection fraction.

Ketone Ester for Treatment Of Acute Heart Failure

Ketones have been suggested to have significant physiological effects in patients with heart failure. Potential mechanisms for these effects include energy provision for the failing heart and direct protective effects on other organs. Despite the strong physiological rationale, the acute effects of ketone therapy in patients with acute heart failure (AHF) is unclear. AHF is a major healthcare issue, with in-hospital mortality exceeding 10%. Therefore, we propose a vanguard randomized controlled trial to assess the effects of ketone esters in patients with AHF. Sixty patients hospitalized with AHF will be randomized to receive either 25 grams of ketone esters three times per day or a matching placebo for five days, or until death or hospital discharge. We hypothesize that ketone therapy will improve markers of systemic congestion and heart failure symptoms. Primary endpoint will be changes in NT-proBNP levels during therapy. Secondary endpoints will be KCCQ scores, and hemodynamic profile as assessed by echocardiogram. Exploratory endpoints will clinical outcomes including mortality, need for intensive care unit admission, among others.

Efficacy and Safety With Early Treatment of Finerenone in Hospitalized Patients With Heart Failure

FACILITATE-HF is a multicenter, randomized, double-blind, placebo-controlled trial designed to determine whether initiation of finerenone during the early phase of hospitalization has beneficial effects in patients with AHF who have left ventricular ejection fraction 40% or more.

Sequential Cystatin C Levels and Renal Impairment in Acute Heart Failure

Renal Compromise after treatment of decompensated heart failure with diuretics is not uncommon. The purpose of our study is to investigate the relationship between cystatin C and worsening renal function in this setting. Cystatin C is a biomarker produced at a constant rate by all cells that is a sensitive biomarker of renal function.Cystatin C and Plasma amino terminal proB-type natriuretic peptide (NT-proBNP) levels will be obtained at baseline and daily. Our goal is to enroll 100 subjects with an estimated 5 samples per each subject. The time course of changes in cystatin C in relation to serum creatinine levels over time will be plotted. Our hypothesis is that sequential changes in cystatin C levels following initial treatment with diuretic therapy in the setting of acute decompensated heart failure may provide early insight into cardio-renal compromise. Understanding the natural history and time course of the changes in sequential cystatin C levels may facilitate further studies to guide the judicious use of diuretic therapy in acute decompensated heart failure, and to predict the risk of subsequent development of worsening renal function. If serial testing of cystatin C can provide accurate assessment and prediction of worsening renal function, clinical applications of these observations can be evaluated in future prospective studies.

Improving Diagnostic Accuracy for Acute Heart Failure

Acute heart failure is a common reason for emergency department visits and hospitalization, but the diagnosis can be challenging because of non-specific symptoms and signs. The current diagnostic approach to acute heart failure has modest accuracy, leading to delayed diagnosis and treatment, which associate with worse prognosis. Prior work suggests diagnostic accuracy can be improved with the addition of multiple circulating biomarkers discovered through proteomics, and this study will derive and validate a multi-marker model to improve diagnostic accuracy for acute heart failure in the emergency department.

Infusion of Furosemide to Improve Diuretic Efficiency in Acute Heart Failure

Acute heart failure is a condition where the heart suddenly cannot pump blood well enough for the body's needs. Many people admitted to the hospital with acute heart failure have too much fluid in the body. This can cause shortness of breath, swelling, and the need for treatment with water-removing medicine. Furosemide is a commonly used water-removing medicine that is given into a vein to treat fluid overload. It can be given in different ways. One way is as a continuous infusion, where the medicine is given slowly over time through a pump. Another way is as repeated injections given several times a day. It is not known whether one of these ways is better than the other for removing excess fluid in people with acute heart failure. The purpose of this study is to compare two ways of giving furosemide into a vein: Continuous infusion started with an initial extra dose, and bolus injections given three times a day. About 436 adults admitted to hospitals in Denmark with acute heart failure and fluid overload will take part. Participants will be randomly assigned to one of the two treatment groups. This means that chance will decide which treatment method each participant receives. The main thing the researchers will measure is how much body weight participants lose about 3 days after randomization. Weight loss is used as a measure of how much excess fluid has been removed.

Dapagliflozin and Effect on Cardiovascular Events in Acute Heart Failure -Thrombolysis in Myocardial Infarction 68 (DAPA ACT HF-TIMI 68)

This is an international, multicenter, parallel-group, randomized, double-blind, placebo-controlled trial in patients who have been stabilized during hospitalization for acute heart failure, evaluating the effect of in-hospital initiation of dapagliflozin versus placebo on the clinical outcome of cardiovascular death or worsening heart failure.

MRI Assessment of Pulmonary Edema in Acute Heart Failure

Researchers are testing a more accurate way to measure how much fluid is in the lungs (also called pulmonary edema, or "increased lung water") in people with Heart Failure (HF) using MRI (Magnetic Resonance Imaging). There is little known about the exact level of lung water in patients with AHF or how these levels change from the time of hospital admission to discharge. The purpose of this research study is to measure the lung water in patients hospitalized for HF, to determine the change in lung water over the course of hospitalization and treatment, and to find out if lung water levels can predict if patients are higher or lower risk for returning to the hospital or dying from heart failure.

Characterisation of phenotYpes in aCute Heart faiLure patiEnts

An observational cohort study to evaluate the benefit of functional parameters, radiomics and blood biomarkers to predict the outcome of patients with acute heart failure.

Investigating aCute heArt failuRe Decongestion Guided by Lung UltraSonography

The goal of this clinical trial is to investigate whether a lung ultrasonography (LUS)-guided decongestion strategy in adults hospitalized for acute heart failure (AHF) can improve patient-centered outcomes. The main questions it aims to answer are: * Does this strategy shorten the length of stay and reduce early hospital readmissions? * Does this strategy improve patients' symptoms and quality of life ? Researchers will compare LUS to physical examination (PE).

Integrating Aerobic, Respiratory, and Cognitive Training in Acute Heart Failure

The purpose of this study is to investigate the impact of integrating aerobic, respiratory and cognitive training in acute heart failure.

Early Treatment With a Sodium-glucose Co-transporter 2 Inhibitor in High-risk Patients With Acute Heart Failure

The EMPA-AHF trial is a multicentre, randomized, double-blind, placebo-controlled trial designed to evaluate the efficacy and safety of early initiation of once-daily oral empagliflozin 10 mg in patients hospitalized for patients with acute heart failure (AHF) who are at a high risk of adverse events.

Prospective Validation of the CoDE-HF Algorithm for the Diagnosis of Acute Heart Failure

Acute heart failure is a life-threatening condition where the heart is suddenly unable to pump blood around the body. It can be challenging to diagnose because the symptoms often mimic other conditions. Previous studies have showed that delays in making the correct diagnosis result in worse outcomes. We therefore developed a decision-support tool called CoDE-HF that uses a computer algorithm to combine levels of a blood test called NT-proBNP with patient factors to calculate the probability of acute heart failure for an individual. In this project, we wish to evaluate the performance of CoDE-HF in approximately 2,000 patients attending the Emergency Department with suspected acute heart failure. We will store surplus material from their blood tests to measure NT-proBNP and link information from their electronic health records with other routinely collected medical information in regional and national databases in order to evaluate this algorithm.

a PRagmatic Observational Study of Congestion proFILes in patiEnts With Acute Heart Failure

The goal of this observational is to study the prevalence of distinct congestion phenotypes and study their association with response to therapy and outcomes in acute heart failure patients. The main question\[s\] it aims to answer \[is/are\]: * Primary objective: to study the prevalence of distinct congestion phenotypes * Other objectives (including): * Response to therapy as assessed by * Natriuresis after 24 hours * Rehospitalization and/or deats after 6 months * Length of hospital stay * Congestion at discharge * Changes in filling pressures over time * Relationship between liver stiffness, as assessed with Fibroscan and congestion * Substudy: glycosaminoglycan netword and endothial glycocalyx Participants will undergo several extra study related measurements: * Assessment of filling pressures with ultrasound * Ultrasound investigation of the lungs and kidneys * Fibroscan of the liver * Sidestream darkfield imaging sublingual * As part of substudy GLYCO-AHF: skin biopsy to determine glycocalyx, as well as salt and water content. * As part of substudy PREACH-AHF: the effects of peripheral venous congestion and endothelial dysfunction on a large screen of plasma proteins