Heart Failure
Conditions
Keywords
heart failure, congestion, ambulatory treatment, remote telemonitoring, diuretics
Brief summary
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
DRUGAcetazolamide
Oral acetazolamide initiated at 500 mg (2 tablets) on Day 0. The dose may be adjusted every 48 hours according to the participant's clinical status until Day 5, if necessary.
DRUGFurosemide
Standard treatment with loop diuretics (furosemide) administered for up to 5 days according to standard clinical practice.
Sponsors
University Hospital, Montpellier
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This multicenter, prospective, randomized, controlled, open-label, superiority Phase III trial compares two parallel groups: standard decongestion with loop diuretics (control group) versus standard decongestion plus oral acetazolamide (experimental group) in ambulatory patients with decompensated heart failure monitored by remote telemonitoring.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of participants with weight loss >2 kg at Day | Day 5 | Percentage of participants who achieve a body weight loss greater than 2 kg between baseline (Day 0) and Day 5, measured using a connected scale through the remote telemonitoring system. Comparison between the experimental and control groups. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy : All-cause mortality | Day 90 | Percentage of participants who die from any cause. |
| Efficacy : All-cause mortality and Heart failure-related mortality | Day 90 | Percentage of participants who die any cause or from heart failure during follow-up. |
| Efficacy : Change in clinical congestion parameters | At Day 15 | Evolution of clinical congestion including body weight, dyspnea VAS score, blood pressure, heart rate, and signs of right- and left-sided heart failure collected during follow-up visits. |
| Safety : Change in serum sodium concentration | Day 0 to Day 5 | Assessment of the change in serum sodium concentration between baseline Day 0 and Day 5 to evaluate electrolyte disturbances associated with treatment. |
| Safety : Percentage of participants with serum sodium <125 mmol/L | Day 5 | Percentage of participants presenting severe hyponatremia, defined as a serum sodium concentration below 125 mmol/L, on Day 5. |
| Safety: Incidence of acute kidney injury (KDIGO stage ≥2) | Day 0 to Day 5 | Percentage of participants developing acute kidney injury defined as Kidney Disease: Improving Global Outcomes (KDIGO) stage 2 or higher between D0 and D5. |
| Safety : Change in serum potassium concentration | Day 0 to Day 5 | Assessment of the change in serum potassium concentration between baseline Day 0 and Day 5 to evaluate treatment related electrolyte abnormalities. |
| Safety: Percentage of participants with serum potassium <2.5 mmol/L | Day 5 | Percentage of participants presenting severe hypokalemia, defined as a serum potassium concentration below 2.5 mmol/L, on Day 5. |
| Safety: Change in serum bicarbonate concentration from Day 0 to Day 5 | Day 0 to Day 5 | Assessment of the change in serum bicarbonate concentration between baseline Day 0 and Day 5 to evaluate metabolic changes associated with treatment. |
| Percentage of participants with serum bicarbonate <20 mmol/L | Day 5 | Percentage of participants presenting serum bicarbonate concentrations below 20 mmol/L on Day 5. |
| Safety: Change in systolic blood pressure | Day 0 to Day 5 | Assessment of the change in systolic blood pressure between baseline Day 0 and Day 5 during treatment. |
| Safety: Percentage of participants with systolic blood pressure <90 mmHg | Day 0 to day 5 | Percentage of participants presenting systolic blood pressure below 90 mmHg during treatment. |
| Safety: Incidence of low cardiac output or cardiogenic shock | Day 0 to Day 5 | Percentage of participants developing low cardiac output syndrome or cardiogenic shock between D0 and D5. |
| Safety: Hospitalization due to treatment failure or poor treatment tolerance | Day 5 and Day 15 | Percentage of participants requiring hospitalization because of treatment failure or poor treatment tolerance. |
| Medicoeconomic: Hospital medical costs | Day 90 | Difference in direct hospital medical costs related to unplanned consultations, emergency department visits, or hospitalizations between the experimental and control groups. Costs will be assessed using actual reimbursement tariffs and hospital revenues. |
| Efficacy : Percentage of weight variation | Day 0 to Day 5 | Percentage change in body weight between Day 0 and Day 5 measured using a connected scale through the remote telemonitoring system. |
| Efficacy : Diuretic effectiveness | Day 5 | Diuretic effectiveness assessed by urinary sodium excretion (natriuresis) corrected for loop diuretic exposure, expressed according to furosemide-equivalent dose administered up to Day 5. |
| Efficacy : Change in NT-proBNP concentration | Day 0 to Day 5 | Change in plasma NT-proBNP concentration measured from blood samples between baseline and Day 5. |
| Efficacy : Change in health-related quality of life (EQ-5D-5L) | Day 0 to Day 5 | Change in EQ-5D-5L score between baseline (Day 0) and Day 5. The EQ-5D-5L is a validated generic quality-of-life questionnaire assessing five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression).Each question has 5 levels of answers: No problem, slight problems, moderate problems, severe problems and unable to/ extreme problems. It also includes a visual analogue scale ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). |
| Efficacy : Rate of unplanned consultation or hospitalization for heart failure | Day 90 | Percentage of participants requiring an unplanned medical consultation, emergency department visit, or hospitalization for heart failure |
| Efficacy : Change in dyspnea Visual Analogue Scale (VAS) score | Day 0 to Day 5 | Change in dyspnea severity assessed using a Visual Analogue Scale (VAS) between baseline (Day 0) and Day 5. The VAS ranges from 0 (no shortness of breath) to 10 (worst shortness of breath imaginable). |
Countries
France
Contacts
CONTACTFrançois ROUBILLE, MD
CONTACTClément Delmas, MD
STUDY_DIRECTORFrançois ROUBILLE, MD
University Hospital, Montpellier
Outcome results
None listed