Heart Failure AcuteACME-AHFNCT06273397
Acetazolamide or Metolazone in Acute Heart Failure
A study testing Acetazolamide 250 MG, Metolazone 2.5 MG and Furosemide Injection in people with Heart Failure Acute and Decompensated Heart Failure, run by Clinica Alemana de Santiago.
Trial summary
Impact of Acute Heart Failure: According to the World Health Organization (WHO), approximately 26 million people suffer from Heart Failure (HF), with a mortality rate of up to 50% within five years of diagnosis. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure Acute, Decompensated Heart Failure
- What is being tested?
- Acetazolamide 250 MG, Metolazone 2.5 MG and Furosemide Injection
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,050 participants
- Where
- No sites listed yet
- Study dates
- 1 May 2024to 1 May 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Acute heart failure: Hospitalization due to symptoms of heart failure, congestion signs documented with a congestion score greater than 1, NT-proBNP above 1000 pg/ml.
- Randomization within 24 hours of admission.
Who cannot join
- Under 18 years of age.
- Received more than one dose of intravenous furosemide before randomization.
- Cause of heart failure: hypertrophic or restrictive cardiomyopathy, or constrictive pericarditis.
- Acute coronary syndrome or severe acute valvulopathy as the cause of decompensation.
- Systolic blood pressure < 90mmHg before randomization.
- Requirement for vasopressors, inotropes, or invasive mechanical ventilation. Use of intravenous vasodilators or non-invasive mechanical ventilation is allowed.
Show all 12Show fewer
- Glomerular filtration rate < 20ml/min/1.73m2.
- Potassium < 2.5 mEQ/L or Sodium < 125 mEQ/L before randomization.
- pH < 7.2 or Bicarbonate < 15mEQ/L before randomization.
- Use of another diuretic in addition to furosemide before randomization. Dapagliflozin or Empagliflozin can be maintained upon admission or initiated early during hospitalization if desired by the treating physician (variable to be recorded).
- Patients who cannot achieve adequate recording of variables (e.g., inability to quantify diuresis or weight).
- Pregnant or lactating individuals. If of childbearing age and there is inconsistency with contraceptive use or reasonable doubts about current pregnancy, a pregnancy test must be conducted before study entry.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Impact of Acute Heart Failure:
According to the World Health Organization (WHO), approximately 26 million people suffer from Heart Failure (HF), with a mortality rate of up to 50% within five years of diagnosis. Acute Heart Failure (AHF) exacerbations, leading to hospitalization, are common and represent the primary cause of hospital admissions in those over 65. Effective decongestion during hospitalization is crucial, as failure to achieve it doubles the risk of rehospitalization and mortality, incurring significant healthcare costs.
Read more
Use of Diuretics in Acute Heart Failure:
Diuretics, particularly loop diuretics like furosemide, are a cornerstone in managing AHF by inducing natriuresis and achieving decongestion. Clinical experience supports their use, though limited clinical trials exist. Pharmacological concepts guide their administration, emphasizing intravenous delivery in high doses and adjusting subsequent doses based on decongestive efficacy. Additionally, sequential tubular blockade with other diuretics like metolazone and acetazolamide is explored to enhance decongestion.
Use of Metolazone and Acetazolamide:
Sequential tubular blockade, using metolazone and acetazolamide in conjunction with furosemide, aims to achieve rapid and effective decongestion. While metolazone targets the distal tubule, inhibiting sodium-chloride channels, acetazolamide affects proximal tubular function. Studies like ADVOR (acetazolamide) and CLOROTIC (thiazide-like diuretic) demonstrate the potential benefits of combining these diuretics for quicker decongestion but with potential risks (in the case of Hydrochlorothiazide).
Outcomes Measured by Major Studies:
Recent studies assessing decongestion in AHF reveal a lack of uniformity in outcome selection. The primary focus should be on reducing rehospitalizations and post-discharge mortality by achieving effective decongestion. The ADVOR study, using a simple congestion score based on clinical and imaging criteria, underscores the importance of reaching a congestion score of 0 or 1 promptly.
Congestion Monitoring:
Monitoring diuretic treatment solely based on clinical aspects may not capture subclinical congestion, necessitating biochemical and imaging parameters. The ACME-AHF trial proposes a diagnostic score integrating clinical and imaging aspects to evaluate congestion status. Secondary outcomes include cumulative diuresis, weight loss, diuretic efficiency, and natriuresis, with a focus on natriuresis as a reliable physiological parameter for decongestion.
Aim of the study:
The ACME-AHF trial is designed to compare the efficacy and safety of two diuretic combination strategies: acetazolamide with furosemide and metolazone with furosemide. The primary objective is to relieve congestion, assessed using a congestion score, within the first three days of treatment during an hospitalization for acute heart failure.
Read the detailed description
After inclusion in the study and signing the informed consent, the patient will be randomized into one of the following three intervention groups:
- Group A: Intravenous furosemide alone.
- Group B: Intravenous furosemide with oral metolazone 2.5mg.
- Group C: Intravenous furosemide with oral acetazolamide 250mg.
Metolazone or acetazolamide will be administered in fixed doses for a total of 3 doses (D0, D1, and D2) - at admission (D0), on the morning of the second day (D1), and on the morning of the third day (D2).
The use of intravenous furosemide will follow a protocol for dose and frequency of administration. Its dose should not be modified before D2. On D2, modification is allowed according to the protocol (details later).
In cases of major adverse events only, the local practitioner may suspend these therapies (as indicated later).
The study is driven by a clinical outcome based on a congestion score. The primary outcome will assess the ability to achieve effective decongestion (score 0 - 1) for each of the three interventions over 3 days. The primary outcome will be considered achieved if a score of 0 - 1 is reached on D1, D2, or D3, without requiring escalation of diuretic therapy on D2. The congestion score consists of 3 clinical parameters (edema, jugular venous distension, lung crepitations), one radiological parameter (pleural effusion on X-ray), and one ultrasonographic parameter (LUS: B-line count in 4 zones). A score is assigned based on the intensity of each parameter, with 0 and 1 considered as a score indicative of complete decongestion.
The key determinant on D0, D1, and D2, guiding whether the intervention continues or stops, is the persistence of congestion. The intervention should continue for those with a congestion score of 2 or more during the first assessment of the day. If the congestion score is 0 or 1, the intervention is suspended, and the patient should transition to oral furosemide (in preparation for hospital discharge).
Here is the detailed procedure for each day of intervention (total 3 days, closing on the third morning of hospitalization or D3):
- D0 or admission day: Eligibility criteria are reviewed for study inclusion, informed consent is obtained, and randomization to the intervention arm is conducted. Admission data is collected.
- D1 or first morning after admission: Congestion score is calculated. In case the primary outcome is not achieved, the intervention continues without modifications. Clinical and biochemical data are collected according to the protocol.
- D2 or second morning of hospitalization: Congestion score is calculated, and the intervention continues in case the primary outcome is not achieved. On this day, decongestive therapy is titrated based on the total diuresis and weight loss achieved in the previous 24 hours (according to the protocol).
- D3 or third morning: Congestion score is calculated. The intervention is discontinued regardless of the achieved score. Further management is at the discretion of the treating physician. Clinical and biochemical data for the last day are collected.
- 90-day Follow-up: The patient will be contacted, and the medical records will be reviewed to assess clinical and biochemical data 90 days after discharge. Information on worsening heart failure and mortality during this period will be extracted.
Additional recommendations for the intervention include:
- Optimal Medical Treatment: Maintain chronic heart failure therapy (ACEI/ARNI/ARB, Beta-blockers, Mineralocorticoid receptor antagonists, and SGLT2 inhibitors) unless contraindicated. Initiate these treatments before discharge, if not already instituted. Encourage early medical follow-up for discharged patients. Decisions on ferric carboxymaltose administration and entry into cardiac rehabilitation are at the physician's discretion.
- Potassium Control: Suggested to keep plasma levels above 4.0 mEQ/L (oral or intravenous correction).
- Patient Diet and Mobilization: Recommend restricting sodium and volume to less than 1.5g and 2000cc daily, respectively. Encourage early mobilization and kinesiotherapy, if no contraindications. Provide thromboembolic prevention based on local guidelines.
- Situations for Intervention Cessation: (protocol termination and AE reporting)
- Hypokalemia < 2.5 mEQ/L
- Hyponatremia < 125 mEQ/L
- Acidosis with pH < 7.20 or Bicarbonate < 15 mEQ/L
- Asymptomatic hypotension (SBP < 90mmHg) or symptomatic hypotension (SBP < 100mmHg).
- Significant deterioration in renal function (creatinine rise above 0.8mg and 1.5x baseline) NOTE: If early intervention suspension occurs with complete decongestion, consider the primary outcome achieved.
- Conditions
- Heart Failure Acute, Decompensated Heart Failure
- Being tested
- Acetazolamide 250 MG, Metolazone 2.5 MG, Furosemide Injection
- Keywords
- Acetazolamide, Metolazone, Heart Failure Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Acetazolamide 250 MGDrug
Acetazolamide 250mg orally per day plus furosemide as per protocol. The intervention is administered on the day of hospital admission and for two consecutive mornings. The total intervention consists of 3 doses. The intervention is discontinued on the third morning. The calculation of the congestion score is performed every morning until the third morning. If complete decongestion is achieved, the primary outcome will be considered fulfilled.
Metolazone 2.5 MGDrug
Metolazone 2.5mg orally per day plus furosemide as per protocol. The intervention is administered on the day of hospital admission and for two consecutive mornings. The total intervention consists of 3 doses. The intervention is discontinued on the third morning. The calculation of the congestion score is performed every morning until the third morning. If complete decongestion is achieved, the primary outcome will be considered fulfilled.
Furosemide InjectionDrug
Intravenous furosemide in a double daily dose. The dosage is determined by a predefined table based on the admission renal function and the outpatient dose prior to admission. In general terms, for patients with an estimated glomerular filtration rate above 60 ml/min/1.73m² or those experiencing heart failure debut, the dose will be 1x the outpatient dose. For those with a glomerular filtration rate below 60 ml/min/1.73m², the dose will be 2x the outpatient dose. The dosing protocol for this arm also serves as guidance for furosemide in the intervention arms.
| Study group | Role | What they receive |
|---|---|---|
| Furosemide alone | Active comparator | Active comparator arm with intravenous furosemide dosing based on glomerular filtration rate (protocol). Receives: Drug: Furosemide Injection |
| Acetazolamide plus Furosemide | Experimental | Experimental arm number 1 corresponds to oral acetazolamide 250mg (once daily) in combination with furosemide according to the protocol. Receives: Drug: Acetazolamide 250 MG; Drug: Furosemide Injection |
| Metolazone plus Furosemide | Experimental | Experimental arm number 2 corresponds to oral metolazone 2.5mg (once daily) in combination with furosemide according to the protocol. Receives: Drug: Metolazone 2.5 MG; Drug: Furosemide Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment success
Complete decongestion by the third morning without requiring escalation in diuretic therapy (by the second morning).
Measured: 4 days
Secondary outcomes (8)
Mortality
All-cause mortality during the first 3 months after start of the study
Measured: 3 months
Worsening Heart Failure
Readmission for Heart Failure or Urgent visit for Heart Failure during the first 3 months after start of the study
Measured: 3 months
Cumulative 24-hour Natriuresis
Natriuresis measured on the second day
Measured: Day 2
Cumulative weight loss
Cumulative weight loss by the third morning
Measured: 4 days
Subclinical congestion
Congestion score will be the score used in the study to evaluate the primary outcome. The calculated scores can range from 0 to 12 points, with 0 indicating absence of congestion and 12 representing the highest degree of congestion. The primary outcome will be defined as achieving a score of 0 or 1 and also having absence of B-lines in the lung ultrasound (negative LUS criterion). In this secondary outcome, the presence of subclinical congestion will be evaluated, which is defined as a congestion score of 0 or 1 but with a positive LUS.
Measured: 4 days
Change in Hematocrit value
Change in Hematocrit
Measured: 4 days
Change in NT-proBNP concentration
Change in NT-proBNP
Measured: 4 days
Change in CA125 value
Change in CA125
Measured: 4 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Feb 2024
- Study start1 May 2024 (estimated)
- Primary completion1 Mar 2027 (estimated)
- Study completion1 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Heart Failure AcuteStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is an Open, Multicenter, Prospective, and Randomized study with three treatment arms. The outcomes to be assessed in the initial phase will be at 4 days post-randomization, followed by evaluation at 90 days after hospital discharge.
- Masking
- None (open label)
- Enrolment
- 1,050 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Clinica Alemana de Santiago
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06273397
- Sponsor's protocol ID
- ACME-AHF
- Acronym
- ACME-AHF
- Status last verified
- Mar 2024
- First submitted
- 31 Jan 2024
- Last updated
- 18 Mar 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Rivas-Lasarte M, Maestro A, Fernandez-Martinez J, Lopez-Lopez L, Sole-Gonzalez E, Vives-Borras M, Montero S, Mesado N, Pirla MJ, Mirabet S, Fluvia P, Brossa V, Sionis A, Roig E, Cinca J, Alvarez-Garcia J. Prevalence and prognostic impact of subclinical pulmonary congestion at discharge in patients with acute heart failure. ESC Heart Fail. 2020 Oct;7(5):2621-2628. doi: 10.1002/ehf2.12842. Epub 2020 Jul 7.
PubMed 32633473Urbich M, Globe G, Pantiri K, Heisen M, Bennison C, Wirtz HS, Di Tanna GL. A Systematic Review of Medical Costs Associated with Heart Failure in the USA (2014-2020). Pharmacoeconomics. 2020 Nov;38(11):1219-1236. doi: 10.1007/s40273-020-00952-0.
PubMed 32812149Felker GM, Ellison DH, Mullens W, Cox ZL, Testani JM. Diuretic Therapy for Patients With Heart Failure: JACC State-of-the-Art Review. J Am Coll Cardiol. 2020 Mar 17;75(10):1178-1195. doi: 10.1016/j.jacc.2019.12.059.
PubMed 32164892Felker GM, Lee KL, Bull DA, Redfield MM, Stevenson LW, Goldsmith SR, LeWinter MM, Deswal A, Rouleau JL, Ofili EO, Anstrom KJ, Hernandez AF, McNulty SE, Velazquez EJ, Kfoury AG, Chen HH, Givertz MM, Semigran MJ, Bart BA, Mascette AM, Braunwald E, O'Connor CM; NHLBI Heart Failure Clinical Research Network. Diuretic strategies in patients with acute decompensated heart failure. N Engl J Med. 2011 Mar 3;364(9):797-805. doi: 10.1056/NEJMoa1005419.
PubMed 21366472Mullens W, Dauw J, Martens P, Verbrugge FH, Nijst P, Meekers E, Tartaglia K, Chenot F, Moubayed S, Dierckx R, Blouard P, Troisfontaines P, Derthoo D, Smolders W, Bruckers L, Droogne W, Ter Maaten JM, Damman K, Lassus J, Mebazaa A, Filippatos G, Ruschitzka F, Dupont M; ADVOR Study Group. Acetazolamide in Acute Decompensated Heart Failure with Volume Overload. N Engl J Med. 2022 Sep 29;387(13):1185-1195. doi: 10.1056/NEJMoa2203094. Epub 2022 Aug 27.
PubMed 36027559Trullas JC, Morales-Rull JL, Casado J, Carrera-Izquierdo M, Sanchez-Marteles M, Conde-Martel A, Davila-Ramos MF, Llacer P, Salamanca-Bautista P, Perez-Silvestre J, Plasin MA, Cerqueiro JM, Gil P, Formiga F, Manzano L; CLOROTIC trial investigators. Combining loop with thiazide diuretics for decompensated heart failure: the CLOROTIC trial. Eur Heart J. 2023 Feb 1;44(5):411-421. doi: 10.1093/eurheartj/ehac689.
PubMed 36423214Appiani F. [Monitoring decongestion in acute heart failure]. Rev Med Chil. 2022 Apr;150(4):493-504. doi: 10.4067/S0034-98872022000400493. Spanish.
PubMed 36155759
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Acetazolamide or Metolazone in Acute Heart Failure
- ClinicalTrials.gov ID
- NCT06273397
- Acronym / sponsor ID
- ACME-AHF / ACME-AHF
- Conditions
- Heart Failure Acute, Decompensated Heart Failure
- Keywords
- Acetazolamide, Metolazone, Heart Failure Acute
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 1,050 participants (estimated)
- Lead sponsor
- Clinica Alemana de SantiagoUniversity, hospital or other
- Study start
- 1 May 2024 (estimated)
- Primary completion
- 1 Mar 2027 (estimated)
- Study completion
- 1 May 2027 (estimated)
- First posted
- 22 Feb 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Impact of Acute Heart Failure:
According to the World Health Organization (WHO), approximately 26 million people suffer from Heart Failure (HF), with a mortality rate of up to 50% within five years of diagnosis. Acute Heart Failure (AHF) exacerbations, leading to hospitalization, are common and represent the primary cause of hospital admissions in those over 65. Effective decongestion during hospitalization is crucial, as failure to achieve it doubles the risk of rehospitalization and mortality, incurring significant healthcare costs.
Use of Diuretics in Acute Heart Failure:
Diuretics, particularly loop diuretics like furosemide, are a cornerstone in managing AHF by inducing natriuresis and achieving decongestion. Clinical experience supports their use, though limited clinical trials exist. Pharmacological concepts guide their administration, emphasizing intravenous delivery in high doses and adjusting subsequent doses based on decongestive efficacy. Additionally, sequential tubular blockade with other diuretics like metolazone and acetazolamide is explored to enhance decongestion.
Use of Metolazone and Acetazolamide:
Sequential tubular blockade, using metolazone and acetazolamide in conjunction with furosemide, aims to achieve rapid and effective decongestion. While metolazone targets the distal tubule, inhibiting sodium-chloride channels, acetazolamide affects proximal tubular function. Studies like ADVOR (acetazolamide) and CLOROTIC (thiazide-like diuretic) demonstrate the potential benefits of combining these diuretics for quicker decongestion but with potential risks (in the case of Hydrochlorothiazide).
Outcomes Measured by Major Studies:
Recent studies assessing decongestion in AHF reveal a lack of uniformity in outcome selection. The primary focus should be on reducing rehospitalizations and post-discharge mortality by achieving effective decongestion. The ADVOR study, using a simple congestion score based on clinical and imaging criteria, underscores the importance of reaching a congestion score of 0 or 1 promptly.
Congestion Monitoring:
Monitoring diuretic treatment solely based on clinical aspects may not capture subclinical congestion, necessitating biochemical and imaging parameters. The ACME-AHF trial proposes a diagnostic score integrating clinical and imaging aspects to evaluate congestion status. Secondary outcomes include cumulative diuresis, weight loss, diuretic efficiency, and natriuresis, with a focus on natriuresis as a reliable physiological parameter for decongestion.
Aim of the study:
The ACME-AHF trial is designed to compare the efficacy and safety of two diuretic combination strategies: acetazolamide with furosemide and metolazone with furosemide. The primary objective is to relieve congestion, assessed using a congestion score, within the first three days of treatment during an hospitalization for acute heart failure.
Detailed description
After inclusion in the study and signing the informed consent, the patient will be randomized into one of the following three intervention groups:
- Group A: Intravenous furosemide alone.
- Group B: Intravenous furosemide with oral metolazone 2.5mg.
- Group C: Intravenous furosemide with oral acetazolamide 250mg.
Metolazone or acetazolamide will be administered in fixed doses for a total of 3 doses (D0, D1, and D2) - at admission (D0), on the morning of the second day (D1), and on the morning of the third day (D2).
The use of intravenous furosemide will follow a protocol for dose and frequency of administration. Its dose should not be modified before D2. On D2, modification is allowed according to the protocol (details later).
In cases of major adverse events only, the local practitioner may suspend these therapies (as indicated later).
The study is driven by a clinical outcome based on a congestion score. The primary outcome will assess the ability to achieve effective decongestion (score 0 - 1) for each of the three interventions over 3 days. The primary outcome will be considered achieved if a score of 0 - 1 is reached on D1, D2, or D3, without requiring escalation of diuretic therapy on D2. The congestion score consists of 3 clinical parameters (edema, jugular venous distension, lung crepitations), one radiological parameter (pleural effusion on X-ray), and one ultrasonographic parameter (LUS: B-line count in 4 zones). A score is assigned based on the intensity of each parameter, with 0 and 1 considered as a score indicative of complete decongestion.
The key determinant on D0, D1, and D2, guiding whether the intervention continues or stops, is the persistence of congestion. The intervention should continue for those with a congestion score of 2 or more during the first assessment of the day. If the congestion score is 0 or 1, the intervention is suspended, and the patient should transition to oral furosemide (in preparation for hospital discharge).
Here is the detailed procedure for each day of intervention (total 3 days, closing on the third morning of hospitalization or D3):
- D0 or admission day: Eligibility criteria are reviewed for study inclusion, informed consent is obtained, and randomization to the intervention arm is conducted. Admission data is collected.
- D1 or first morning after admission: Congestion score is calculated. In case the primary outcome is not achieved, the intervention continues without modifications. Clinical and biochemical data are collected according to the protocol.
- D2 or second morning of hospitalization: Congestion score is calculated, and the intervention continues in case the primary outcome is not achieved. On this day, decongestive therapy is titrated based on the total diuresis and weight loss achieved in the previous 24 hours (according to the protocol).
- D3 or third morning: Congestion score is calculated. The intervention is discontinued regardless of the achieved score. Further management is at the discretion of the treating physician. Clinical and biochemical data for the last day are collected.
- 90-day Follow-up: The patient will be contacted, and the medical records will be reviewed to assess clinical and biochemical data 90 days after discharge. Information on worsening heart failure and mortality during this period will be extracted.
Additional recommendations for the intervention include:
- Optimal Medical Treatment: Maintain chronic heart failure therapy (ACEI/ARNI/ARB, Beta-blockers, Mineralocorticoid receptor antagonists, and SGLT2 inhibitors) unless contraindicated. Initiate these treatments before discharge, if not already instituted. Encourage early medical follow-up for discharged patients. Decisions on ferric carboxymaltose administration and entry into cardiac rehabilitation are at the physician's discretion.
- Potassium Control: Suggested to keep plasma levels above 4.0 mEQ/L (oral or intravenous correction).
- Patient Diet and Mobilization: Recommend restricting sodium and volume to less than 1.5g and 2000cc daily, respectively. Encourage early mobilization and kinesiotherapy, if no contraindications. Provide thromboembolic prevention based on local guidelines.
- Situations for Intervention Cessation: (protocol termination and AE reporting)
- Hypokalemia < 2.5 mEQ/L
- Hyponatremia < 125 mEQ/L
- Acidosis with pH < 7.20 or Bicarbonate < 15 mEQ/L
- Asymptomatic hypotension (SBP < 90mmHg) or symptomatic hypotension (SBP < 100mmHg).
- Significant deterioration in renal function (creatinine rise above 0.8mg and 1.5x baseline) NOTE: If early intervention suspension occurs with complete decongestion, consider the primary outcome achieved.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- This is an Open, Multicenter, Prospective, and Randomized study with three treatment arms. The outcomes to be assessed in the initial phase will be at 4 days post-randomization, followed by evaluation at 90 days after hospital discharge.
| Arm | Type | Receives |
|---|---|---|
| Furosemide alone | Active comparator | Drug: Furosemide InjectionActive comparator arm with intravenous furosemide dosing based on glomerular filtration rate (protocol). |
| Acetazolamide plus Furosemide | Experimental | Drug: Acetazolamide 250 MG, Drug: Furosemide InjectionExperimental arm number 1 corresponds to oral acetazolamide 250mg (once daily) in combination with furosemide according to the protocol. |
| Metolazone plus Furosemide | Experimental | Drug: Metolazone 2.5 MG, Drug: Furosemide InjectionExperimental arm number 2 corresponds to oral metolazone 2.5mg (once daily) in combination with furosemide according to the protocol. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Acute heart failure: Hospitalization due to symptoms of heart failure, congestion signs documented with a congestion score greater than 1, NT-proBNP above 1000 pg/ml.
- Randomization within 24 hours of admission.
Key exclusion criteria (12 listed)
- Under 18 years of age.
- Received more than one dose of intravenous furosemide before randomization.
- Cause of heart failure: hypertrophic or restrictive cardiomyopathy, or constrictive pericarditis.
- Acute coronary syndrome or severe acute valvulopathy as the cause of decompensation.
- Systolic blood pressure < 90mmHg before randomization.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Acetazolamide 250 MGAcetazolamide 250mg orally per day plus furosemide as per protocol. The intervention is administered on the day of hospital admission and for two consecutive mornings. The total intervention consists of 3 doses. The intervention is discontinued on the third morning. The calculation of the congestion score is performed every morning until the third morning. If complete decongestion is achieved, the primary outcome will be considered fulfilled. | Drug | Acetazolamide plus Furosemide |
| Metolazone 2.5 MGMetolazone 2.5mg orally per day plus furosemide as per protocol. The intervention is administered on the day of hospital admission and for two consecutive mornings. The total intervention consists of 3 doses. The intervention is discontinued on the third morning. The calculation of the congestion score is performed every morning until the third morning. If complete decongestion is achieved, the primary outcome will be considered fulfilled. | Drug | Metolazone plus Furosemide |
| Furosemide InjectionIntravenous furosemide in a double daily dose. The dosage is determined by a predefined table based on the admission renal function and the outpatient dose prior to admission. In general terms, for patients with an estimated glomerular filtration rate above 60 ml/min/1.73m² or those experiencing heart failure debut, the dose will be 1x the outpatient dose. For those with a glomerular filtration rate below 60 ml/min/1.73m², the dose will be 2x the outpatient dose. The dosing protocol for this arm also serves as guidance for furosemide in the intervention arms. | Drug | Acetazolamide plus Furosemide, Furosemide alone, Metolazone plus Furosemide |
Primary outcome
Treatment success
Time frame: 4 days
Complete decongestion by the third morning without requiring escalation in diuretic therapy (by the second morning).
8 secondary outcomes
Mortality
Time frame: 3 months
Worsening Heart Failure
Time frame: 3 months
Cumulative 24-hour Natriuresis
Time frame: Day 2
Cumulative weight loss
Time frame: 4 days
Subclinical congestion
Time frame: 4 days
Change in Hematocrit value
Time frame: 4 days
Change in NT-proBNP concentration
Time frame: 4 days
Change in CA125 value
Time frame: 4 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Mar 2024.
- Background: PubMed 32633473Rivas-Lasarte M, Maestro A, Fernandez-Martinez J, Lopez-Lopez L, Sole-Gonzalez E, Vives-Borras M, Montero S, Mesado N, Pirla MJ, Mirabet S, Fluvia P, Brossa V, Sionis A, Roig E, Cinca J, Alvarez-Garcia J. Prevalence and prognostic impact of subclinical pulmonary congestion at discharge in patients with acute heart failure. ESC Heart Fail. 2020 Oct;7(5):2621-2628. doi: 10.1002/ehf2.12842. Epub 2020 Jul 7.
- Background: PubMed 32812149Urbich M, Globe G, Pantiri K, Heisen M, Bennison C, Wirtz HS, Di Tanna GL. A Systematic Review of Medical Costs Associated with Heart Failure in the USA (2014-2020). Pharmacoeconomics. 2020 Nov;38(11):1219-1236. doi: 10.1007/s40273-020-00952-0.
- Background: PubMed 32164892Felker GM, Ellison DH, Mullens W, Cox ZL, Testani JM. Diuretic Therapy for Patients With Heart Failure: JACC State-of-the-Art Review. J Am Coll Cardiol. 2020 Mar 17;75(10):1178-1195. doi: 10.1016/j.jacc.2019.12.059.
- Background: PubMed 21366472Felker GM, Lee KL, Bull DA, Redfield MM, Stevenson LW, Goldsmith SR, LeWinter MM, Deswal A, Rouleau JL, Ofili EO, Anstrom KJ, Hernandez AF, McNulty SE, Velazquez EJ, Kfoury AG, Chen HH, Givertz MM, Semigran MJ, Bart BA, Mascette AM, Braunwald E, O'Connor CM; NHLBI Heart Failure Clinical Research Network. Diuretic strategies in patients with acute decompensated heart failure. N Engl J Med. 2011 Mar 3;364(9):797-805. doi: 10.1056/NEJMoa1005419.
- Background: PubMed 36027559Mullens W, Dauw J, Martens P, Verbrugge FH, Nijst P, Meekers E, Tartaglia K, Chenot F, Moubayed S, Dierckx R, Blouard P, Troisfontaines P, Derthoo D, Smolders W, Bruckers L, Droogne W, Ter Maaten JM, Damman K, Lassus J, Mebazaa A, Filippatos G, Ruschitzka F, Dupont M; ADVOR Study Group. Acetazolamide in Acute Decompensated Heart Failure with Volume Overload. N Engl J Med. 2022 Sep 29;387(13):1185-1195. doi: 10.1056/NEJMoa2203094. Epub 2022 Aug 27.
- Background: PubMed 36423214Trullas JC, Morales-Rull JL, Casado J, Carrera-Izquierdo M, Sanchez-Marteles M, Conde-Martel A, Davila-Ramos MF, Llacer P, Salamanca-Bautista P, Perez-Silvestre J, Plasin MA, Cerqueiro JM, Gil P, Formiga F, Manzano L; CLOROTIC trial investigators. Combining loop with thiazide diuretics for decompensated heart failure: the CLOROTIC trial. Eur Heart J. 2023 Feb 1;44(5):411-421. doi: 10.1093/eurheartj/ehac689.
- Background: PubMed 36155759Appiani F. [Monitoring decongestion in acute heart failure]. Rev Med Chil. 2022 Apr;150(4):493-504. doi: 10.4067/S0034-98872022000400493. Spanish.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Questions about this trial
What is this clinical trial studying?
A study testing Acetazolamide 250 MG, Metolazone 2.5 MG and Furosemide Injection in people with Heart Failure Acute and Decompensated Heart Failure, run by Clinica Alemana de Santiago.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 18 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Franco Appiani, MD (222101111 ext. +56, fappiani@alemana.cl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Treatment success (time frame: 4 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06273397, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Mar 2024.