Efficacy of Oral Acetazolamide Added to Standard Therapy for Rapid Decongestion in Ambulatory Heart Failure Patients (ACHIEVE Trial)

Primary objective: To determine, at day 5, the efficacy of adding acetazolamide to standard therapy in achieving decongestion in ambulatory heart failure patients already receiving furosemide, as assessed by remote monitoring. This endpoint addresses the urgent need for rapid fluid removal to improve symptoms and reduce early rehospitalization risk. Secondary objectives:

• Compare decongestion over the first 5 days between the acetazolamide‑enhanced regimen and conventional treatment.
• Evaluate diuretic response on day 5.
• Assess change in NT-proBNP from baseline to day 5.
• Measure impact on quality of life and dyspnea during the initial 5‑day period.
• Determine the incidence of emergent or unplanned acute heart failure consultations or hospitalizations by day 90.
• Describe clinical (weight, VAS dyspnea, blood pressure, heart rate, right‑ and left‑sided heart failure signs) and biological decongestion trajectories between days 5 and 15, and at day 15.
• Evaluate and compare the occurrence of adverse effects (including hyponatremia, acute renal failure, hypokalemia, metabolic acidosis, arterial hypotension, low cardiac output/cardiogenic shock) at day 5.
• Record need for hospitalization for treatment failure or intolerance on days 5 and 15.
• Compare hospital medical costs at day 90 between groups.

The sponsor did not provide the total number of participants. The trial enrolled adult patients (age ≥ 18) of both sexes with a diagnosis of heart failure characterized by impaired, mildly reduced, or preserved left ventricular ejection fraction. All participants were receiving guideline‑directed medical therapy per ESC Heart Failure Guidelines, were on furosemide at a dose of ≥20 mg/day for at least 30 days prior to enrollment, and were monitored remotely through daily weight measurements using a connected scale. Inclusion required a recent unplanned hospitalization or emergent consultation for acute decompensated heart failure. Selection was based on these clinical and therapeutic criteria, without additional lifestyle restrictions reported.

The interventional study evaluates the addition of acetazolamide (DIAMOX* 250 mg tablets, 1000 mg total daily dose, oral) to guideline‑directed therapy in patients with Heart failure who are receiving furosemide ≥20 mg/day and are monitored remotely via a connected weight scale. After a screening visit confirming eligibility (age ≥18 years, known HF with any left‑ventricular ejection fraction, ongoing remote monitoring, and recent unplanned HF decompensation), participants enter the baseline visit (Day 0) where random allocation to the experimental group (acetazolamide plus standard care) or control group (standard care alone) is performed. Follow‑up assessments occur on Day 5 (primary efficacy evaluation of weight loss >2 kg, natriuresis, Nt‑proBNP, EQ‑5D‑5L, and dyspnea VAS), Day 15 (clinical and biomarker reassessment), and Day 90 (rates of HF‑related emergency visits, hospitalizations, and all‑cause mortality). The end‑of‑study visit coincides with the Day 90 assessment, concluding a participant involvement period of approximately three months. The trial commenced recruitment on 1 June 2026 and is planned to complete by 1 September 2029.

The investigational product is DIAMOX* 250 mg tablet containing the active ingredient acetazolamide. The medication is administered by oral route with a total daily dose of 1000 mg; the exact timing of each administration follows the study protocol.

Participants assigned to the control arm receive the current standard-of-care for heart failure, which includes the loop diuretic furosemide and any other guideline‑directed therapies deemed appropriate by the treating physician.

Drug administration is recorded in the case report form, and adherence is evaluated through a remote monitoring system that captures dosing times and physiological parameters to ensure compliance with the prescribed regimen.

The trial evaluates the efficacy of acetazolamide added to standard therapy in patients with heart failure by comparing decongestion outcomes between the experimental and control groups. The primary efficacy endpoint is the proportion of participants achieving a weight loss greater than 2 kg, measured with a connected scale via a remote telemonitoring system on day 5 (D5). Secondary endpoints include the percentage of weight change from baseline (D0) to D5, diuretic effectiveness on D5 assessed by natriuresis corrected for furosemide equivalence from a urinary ionogram performed on D5, changes in NT‑proBNP levels between D0 and D5, and evolution of health‑related quality of life measured by the EQ‑5D‑5L and dyspnea visual analogue scale (VAS) between D0 and D5. Additional secondary assessments comprise the rate of unplanned emergency consultations or hospitalizations for heart failure and all‑cause mortality at day 90 (D90), as well as longitudinal clinical and biological evaluations (weight, VAS dyspnea, blood pressure, heart rate, right‑ and left‑handed failure signs, and NT‑proBNP) at D5, D15, and D90.

Efficacy parameters are collected using validated instruments: weight is recorded daily on the remote connected scale; urinary ionograms provide natriuresis data; NT‑proBNP concentrations are measured in certified laboratories; EQ‑5D‑5L and VAS scores are obtained through patient‑reported outcome questionnaires. Data collection occurs at baseline (D0), on day 5, day 15, and follow‑up at day 90, with analyses planned to compare the experimental and control groups using appropriate statistical methods for proportion differences and longitudinal changes.