Acute Heart Failure MedDRA version: 20.0 Level: LLT Classification code 10000803 Term: Acute heart failure System Organ Class: 100000004849
Conditions
Interventions
Trade Name: Diamox
Pharmaceutical Form: Powder and solvent for solution for infusion
INN or Proposed INN: acetazolamide
CAS Number: 59-66-5
Other descriptive name: ACETAZOLAMIDE
Concentration unit: mg
Sponsors
UZ Brussel
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • At least 18 y/o and able to provide informed consent • Hospital admission (anticipated stay >24 h after randomisation) with diagnosis of AHF according to the treating physician • At least one of the following three signs of volume overload: 1) bilateral oedema 2+, indicating clear pitting 2) ascites that is amenable for drainage, confirmed by echography 3) uni- or bilateral pleural effusions that are amenable for drainage, confirmed by chest X-ray or lung ultrasound • Plasma N-terminal of the pro hormone of B type natriuretic peptide (NTproBNP) level >1,000 ng/L Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 52 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 52
Exclusion criteria
Exclusion criteria: • No possibility to collect reliable urine spot samples after diuretic administration • Administration of any diuretic within 6 h before randomisation, except for a mineralocorticoid receptor antagonist (MRA) or sodium glucose co transporter 2 (SGLT2) inhibitor as part of the patient’s maintenance treatment for heart failure • Severe kidney dysfunction, defined as an estimated glomerular filtration rate (eGFR) <15 mL/min/1.73m² calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) formula9 at randomisation, and/or previous, current, or planned future renal replacement therapy • Systolic blood pressure <90 mmHg, mean arterial pressure <65 mmHg, or need for inotropes/vasopressor therapy at randomisation • Any acute coronary syndrome within 30 days prior to enrolment, defined as typical chest pain with a troponin rise above the 99th percentile of normal and/or electrocardiographic changes suggestive of cardiac ischemia • History of heart or kidney transplantation • History of mechanical circulatory support • Known obstructive hypertrophic cardiomyopathy, congenital heart disease, acute mechanical cause of AHF (e.g., papillary muscular rupture), acute myocarditis, or constrictive pericarditis • Pregnant or breastfeeding woman • Concomitant participation in another interventional study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate whether a diuretic regimen with low-treshold use of combination diuretic therapy, based on serial assessment of sodium concentration on spot urine samples after diuretic administration, improves decongestion in AHF.;Secondary Objective: •To provide prospective longitudinal data on the incidence and determinants of diuretic resistance in patients with AHF and low threshold use of combinational diuretic treatment. •To investigate the relationship between hemodynamic congestion (i.e., cardiac filling pressures & diastolic function on transthoracic echocardiography) and urine sodium concentration under appropriately dosed diuretics according to a standardised regimen. •To investigate the relationship between lung congestion (B-lines on lung ultrasound & bioelectrical impedance analysis), as well as abdominal organ congestion (venous Doppler echography & bioelectrical impedance analysis), and urine sodium concentration under appropriately dosed diuretics according to a standardised regimen.;Primary end point(s): The primary study endpoint is the win ratio for a hierarchically composed endpoint. The individual components of this endpoint in order of importance are: 1)Death 2)Non elective hospital readmission 3)Relative NTproBNP decrease;Timepoint(s) of evaluation of this end point: 30 days after discharge from the index hospitalization | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Relative NTproBNP decrease from baseline to 30 days after discharge [%] • Relative cancer antigen 125 (CA 125) from baseline to 30 days after discharge [%] • Length of intravenous diuretic therapy [days] • Successful decongestion defined as no more than trace oedema, absence of jugular venous distension and no rales upon the moment of transition from intravenous diuretics to oral maintenance therapy • Five point Likert scale for overall well being assessed upon the transition from intravenous diuretics to oral maintenance therapy compared to the moment of randomization (much improved/slightly improved/neutral/slightly worse/much worse) • Doubling of the serum creatinine or plasma cystatin C compared to baseline with an absolute value >2 mg/dL or >2 mg/L, respectively, or the need for ultrafiltration and/or renal replacement therapy during the index hospital admission (renal safety end point) • Systolic blood pressure <90 mmHg or mean arterial pressure <65 mmHg or need for vasopressors and/or inotropes during the index hospital admission (hemodynamic safety endpoint) • Length of the index hospital admission [days] • Death, non elective rehospitalization or non elective medical contact • Death or non elective hospital readmission rate;Timepoint(s) of evaluation of this end point: 30 days after discharge from the index hospitalization | — |
Countries
Belgium
Contacts
Public ContactCentrum voor Hart- en Vaatziekten
UZ Brussel
Outcome results
None listed