Acetazolamide in Patients With Acute Heart Failure (ACETA)

Prospective Analysis Between Acetazolamide vs Placebo in Patients With Acute Heart Failure

Introduction: Recent studies have suggested that the use of acetazolamide may assist in the vol- ume management of patients with decompensated heart failure (HF). However, prospective and randomized comparison in patients with HF and optimized diuretic therapy has not been described. Objective: The aim of this study was to evaluate the effectiveness and safety of the use of acetazolamide versus placebo in volume control in patients with decompensated HF. Methodology: For this, a unicentric, randomized, double blind and prospective study will be performed in a comparative manner. Hospital data (test results, medical outcomes, drug dose, complications) of patients will be analyzed for safety and effectiveness. Expected results: The use of acetazolamide as an adjuvant treatment is superior to the standard strategy for volume control in patients with decompensated HF.

Study Overview

• Status: Unknown
• Conditions: Heart Failure; Acute Heart Failure
• Intervention / Treatment: Drug: Acetazolamide; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • São Paulo, Brazil, 05403000
    • Recruiting
    • Instituto do Coração - HMFMUSP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult men and women aged> 18 years.
• Patients with LVEF ≤ 40% documented on echocardiography
• BNP> 500 pg / mL
• Signed consent form.

Exclusion Criteria:

• Pregnancy
• COPD
• Hepatical cirrhosis
• Known allergy to acetazolamide
• 2nd or 3rd degree atrioventricular block.
• SBP <90 mmHg or need for vasopressor / inotropic use.
• Body mass index greater than 40 kg / m2.
• Acute coronary syndrome.
• Orotracheal intubation.
• Presence of significant pericardial effusion.
• Left ventricular outflow tract obstruction.
• Serum creatinine> 5.0 mg / dL, creatinine clearance <10 mL / min or hemodialysis.

• Presence of 2 or more clinical / laboratory / radiological criteria of infection defined by:

  • Fever
  • Leukocyte> 12,000 / mm3 or> 10% of young forms,
  • Disuria
  • Productive cough
  • Bacteremia
  • Inflammatory / infectious skin lesions
  • Abdominal pain with signs of peritonitis
  • Radiological image of pneumonia.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Acetazolamide; All patients will receive an initial dose of intravenous furosemide of 1mg / kg, subsequently descaled to 0.5mg / kg of 6 / 6h, associated with oral hydrochlorothiazide 25mg / day and spironolactone 25mg / day orally. When the patient is randomized to the acetazolamide group, he / she will start using the adjuvant medication as acetazolamide drug capsule at the daily dose of 250 mg / day (oral) during the first three days of treatment.	Drug: Acetazolamide; Patient will follow the treatment according to inclusion sequence, receiving the corresponding number medication.
EXPERIMENTAL: Placebo; All patients will receive an initial dose of intravenous furosemide of 1mg / kg, subsequently descaled to 0.5mg / kg of 6 / 6h, associated with oral hydrochlorothiazide 25mg / day and spironolactone 25mg / day orally. When the patient is randomized to the placebo group, he / she will start using the placebo drug capsule during the first three days of treatment.	Drug: Placebo; Patient will follow the treatment according to inclusion sequence, receiving the corresponding number medication.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
diuresis and negative water balance	The comparison between groups for diuresis and negative water balance	72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of cases with worsening of renal function	worsening of renal function (increase of 0.5 mg / dl or 25% increase in relation to admission creatinine)	72 hours
Number of cases with lowering of consciousness level	lowering of consciousness level	72 hours
Number of cases with circulatory assistance	need for mechanical circulatory assistance	72 hours
Number of cases with vasopressor	need for vasopressor or inotropic association	72 hours
Number of cases with orotracheal intubation	need for orotracheal intubation	72 hours
Number of cases with arrhythmia	occurrence of sustained ventricular arrhythmia	72 hours
Number of cases with acetazolamide side effects	need for suspension of acetazolamide due to side effects	72 hours
Number of cases of death	ocurrence of death	72 hours
Level of Base excess	Comparison of all hemodynamic / metabolic parameters to be evaluated (base excess)	30 days
Level of bicarbonate	Comparison of all hemodynamic / metabolic parameters to be evaluated	30 days
Rate of systolic and diastolic blood pressure	Comparison of all hemodynamic / metabolic parameters to be evaluated	30 days
Level of cardiac output	Comparison of all hemodynamic / metabolic parameters to be evaluated	30 days
Level of systolic volume	Comparison of all hemodynamic / metabolic parameters to be evaluated	30 days
Level of arterial lactate	Comparison of all hemodynamic / metabolic parameters to be evaluated	30 days
Level of BNP	Comparison of all hemodynamic / metabolic parameters to be evaluated	30 days
Level of troponin	Comparison of all hemodynamic / metabolic parameters to be evaluated	30 days
heart rate	Comparison of all hemodynamic / metabolic parameters to be evaluated	30 days
Level of sodium	Comparison of all hemodynamic / metabolic parameters to be evaluated	30 days
Level of potassium	Comparison of all hemodynamic / metabolic parameters to be evaluated	30 days
Level of creatinine	Comparison of all hemodynamic / metabolic parameters to be evaluated	30 days
Level of urea	Comparison of all hemodynamic / metabolic parameters to be evaluated	30 days

Collaborators and Investigators

• Sponsor: University of Sao Paulo General Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 1, 2018
• Primary Completion (ANTICIPATED): October 1, 2019
• Study Completion (ANTICIPATED): October 1, 2020

Study Registration Dates

• First Submitted: October 19, 2018
• First Submitted That Met QC Criteria: October 23, 2018
• First Posted (ACTUAL): October 25, 2018

Study Record Updates

• Last Update Posted (ACTUAL): October 30, 2018
• Last Update Submitted That Met QC Criteria: October 26, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Carbonic Anhydrase Inhibitors; Natriuretic Agents; Diuretics; Anticonvulsants; Acetazolamide
• Other Study ID Numbers: PSInCor-Acetazolamide

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No