ACetazolamide in Patients With Heart Failure, to Decrease Weight and relIEVE Symptoms.

Overview

Acute congestion is common in patients with heart failure (HF) and is associated with impaired renal function, reduced quality of life, hospital readmissions, and mortality. Current guidelines recommend optimal decongestion using diuretic therapy, mainly loop diuretics. Although acetazolamide has recently demonstrated efficacy in hospitalized patients, its role in ambulatory patients managed through remote telemonitoring remains to be established. This study aims to evaluate the efficacy of oral acetazolamide added to conventional treatment for decongesting ambulatory HF patients during congestive decompensations. ACHIEVE is a Phase III multicenter, prospective, interventional, randomized, controlled, open-label superiority trial evaluating the efficacy of oral acetazolamide added to conventional treatment for decongestion in ambulatory patients with heart failure during congestive decompensation monitored by remote telemonitoring. The primary objective is to assess, at Day 5, whether acetazolamide added to conventional treatment improves decongestion compared with standard treatment alone. Secondary objectives include evaluating efficacy, safety, and health economic outcomes, including quality of life, dyspnea, biological markers, unplanned consultations, hospitalizations, mortality, and hospital medical costs.

Interventions

• Drug Acetazolamide and furosemide
  Oral acetazolamide initiated at 500 mg (2 tablets) on Day 0 in addition to standard treatment with loop diuretics. The dose may be adjusted every 48 hours according to the participant's clinical status until Day 5, if necessary.
• Drug Furosemide
  Standard treatment with loop diuretics (furosemide) administered for up to 5 days according to standard clinical practice.

Primary outcome measures

• Percentage of participants with weight loss >2 kg at Day [Time frame: Day 5]

Secondary outcome measures (12)

• Efficacy : Percentage of weight variation [Time frame: Day 0 to Day 5]
• Efficacy : Diuretic effectiveness [Time frame: Day 5]
• Efficacy : Change in NT-proBNP concentration [Time frame: Day 0 to Day 5]
• Efficacy : Change in health-related quality of life (EQ-5D-5L) [Time frame: Day 0 to Day 5]
• Efficacy : Change in dyspnea Visual Analogue Scale (VAS) score [Time frame: Day 0 to Day 5]
• Efficacy : Rate of unplanned consultation or hospitalization for heart failure [Time frame: Day 90]
• Efficacy : All-cause mortality [Time frame: Day 90]
• Efficacy : All-cause mortality and Heart failure-related mortality [Time frame: Day 90]
• Efficacy : Change in clinical congestion parameters [Time frame: At Day 15]
• Efficacy : Change in NT-proBNP concentration [Time frame: At Day 15]
• Safety : Change in serum sodium concentration [Time frame: Day 0 to Day 5]
• Safety : Percentage of participants with serum sodium <125 mmol/L [Time frame: Day 5]

Eligibility criteria

Inclusion criteria

• Age ≥ 18
• Known HF with impaired, midly-reduced or preserved LVEF
• Under guideline directed medical therapy for HF according to ESC Heart Failure Guidelines applicable at inclusion
• Previously followed (or included at hospital discharge) by remote monitoring allowing daily weight by connected scale (i.e. Careline®, Optified-self®, NewCard®, Implicity®)
• Under furosemide diuretic treatment ≥ 20mg/day for at least 30 days prior to inclusion
• Current unplanned hospitalization or unplanned/emergent consultation for acute/decompensation HF

Exclusion criteria

• Subject unable to express their consent and sign informed consent form
• Subject not covered by public health insurance
• Refusal to participate (absence of informed consent).
• Subject under guardianship, legal protection, or deprived of liberty.
• Pregnant or breastfeeding women.
• Subject under law protection and prisoners
• Women of child bearing potential, unless they are using an effective method of birth control (i.e. oral contraceptives, implantable contraceptives, injectable contraceptives, transdermal contraceptives, intrauterine devices, male or female condoms with spermicide, abstinence, or a sterile sexual partner)
• Subject unable to comprehend or adhere to the protocol and follow-up
• Concurrent participation in another interventional study.
• Chronic ventricular assist device or heart transplant patients.
• Acute heart failure from recent acute coronary syndrome (< 1 month).
• Severe chronic renal failure or dialysis (GFR < 20 ml/min).
• History of renal colic, hyperchloremic acidosis and wheat allergy (other than coeliac disease)
• Known severe hepatic insufficiency defined by a PTT < 50% or a Child-Pugh score C and/or a known (clinial or biological) supplemented adrenal insufficiency
• Intolerance to sulphonamides
• Hypersensitivity to the active substance (Acetazolamide) or to any of the excipients (Calcium carbonate, wheat starch, gelatine, magnesium stearate)
• Concomitant use of carbamazepine or quinidinics (hydroquinidine, quinidine)
• Low cardiac output syndrome/cardiogenic shock.
• Current use of acetazolamide or any other carbonic anhydrase inhibitor, including but not limited to topical ophthalmic formulations (e.g., brinzolamide, dorzolamide, methazolamide)
• Concomitant use of lithium, valproic acid and valpromide
• Current use of high-dose aspirin (>300 mg/day).

Non-randomization criteria (Criteria should be controlled before patients' randomization) :

• False alarm
• Time between alarm and randomization > 48h
• Subject who declines his participation
• Loss of study treatments or unable to take it at D0
• Hemodynamic instability justifying an urgent hospitalization
• If applicable, positive urine pregnancy test

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

France · 25 centers

• University Hospital Amiens-Picardie — Amiens
• University Hospital Angers — Angers
• Avignon Hospital — Avignon
• University Hospital Besançon — Besançon
• Hospital Beziers — Béziers
• University Hospital Bordeaux — Bordeaux
• University Hospital Brest — Brest
• University Hospital Caen — Caen
• … and 17 more centers

Identifiers

NCT: NCT07737964 · RECHMPL24_0295 · 2025-524344-35-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗