Acetazolamide Per os for Decompensation of Heart Failure (ORION-A)

The main causes of chronic heart failure (CHF) are arterial hypertension and coronary artery disease, less often cardiomyopathy, pericarditis, metastatic myocardial lesions. It should be noted that up to 50% of patients have a preserved left ventricular ejection fraction (LVEF), while its prevalence is progressively increasing annually.

Acute decompensation of CHF is understood as a rapid increase in the severity of clinical manifestations (shortness of breath, severe arterial hypoxemia, the occurrence of arterial hypotension), which caused urgent medical treatment and emergency hospitalization in a patient already suffering from CHF. Decompensation of CHF requires intensification of treatment in order to stabilize the patient's condition. Strengthening diuretic therapy in addition to standard therapy helps to reduce edematous syndrome.

Study Overview

• Status: Recruiting
• Conditions: Chronic Heart Failure
• Intervention / Treatment: Drug: Acetazolamide

Detailed Description

Chronic heart failure (CHF) is a syndrome caused by a violation of the heart's ability for contraction and relaxation, which is associated with an imbalance of vasoconstrictor and vasodilating neurohormonal systems, leading to hypoperfusion of organs and systems and the appearance of such complaints and signs as shortness of breath, weakness, palpitations, increased fatigue, swelling due to fluid congestion in the body.

An unfavorable prognosis, significant costs associated with excessive hospitalization of patients with this diagnosis require the development of clear criteria for the diagnosis and treatment of this condition. The variety of variants of the course of the disease, heterogeneous clinical characteristics of patients, difficulties in determining predisposing factors, unsufficient data on the pathogenetic features of the development of certain types of decompensation of CHF require an active scientific search in this direction and the development of modern clinically effective algorithms for the diagnosis and treatment of such patients The scientific hypothesis of the present study is that the use of acetazolamide in patients with decompensated HF at the hospital stage is accompanied by a significant regression of congestion compared to standard diuretic therapy (since randomization).

The investigators will anticipate that appointment of acetazolamide is accompanied by a decrease in the manifestation of edema syndrome.

• Study Type: Interventional
• Enrollment (Estimated): 400
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Dmitriy Duplyakov, MD; Phone Number: 89277297273; Email: Duplyakov@yahoo.com
• Study Contact Backup: Name: Olesya Rubanenko, MD; Phone Number: 89371887780; Email: olesya.rubanenko@gmail.com

Study Locations

• Russian Federation
  • Samara, Russian Federation, 443099
    • Recruiting
    • Samara State Medical University
    • Contact: Olesya Rubanenko; Phone Number: 89371887780; Email: olesya.rubanenko@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Men or women aged 18 years and older
• Decompensated CHF NYHA II-IV, which required intravenous administration of diuretics
• Any injection fraction of left ventricle*

• Signed informed consent to participate in the study.

  • in patients with LV LV ≥ 50%: the presence of structural changes of the heart# (left ventricular myocardial hypertrophy, enlargement of the left atrium) and/or diastolic dysfunction# and/or increased levels of BNP or NT-proBNP (BNP > 400 pg/ml or NT-proBNP > 450 pg/ml in persons younger 50 years old; > 900 pg/l in persons 51-75 years old; > 1800 pg/ml older than 75 years) #.

    • criteria according to clinical guidelines 2020 Clinical practice guidelines for Chronic heart failure. Russian Journal of Cardiology. 2020;25(11):4083. (In Russ.) doi:10.15829/1560-4071-2020-4083

Exclusion Criteria:

• Acetazolamide therapy for a month before hospitalization.
• The expected intravenous use of inotropes, vasopressors or sodium nitroprusside at any time of the study.
• Exposure to nephrotoxic agents (e.g. contrast dye) is expected within the next 3 days.
• Hypersensitivity to acetazolamide, other sulfonamides and / or components of the drug.
• Systolic blood pressure <90 mmHg.
• Pregnancy and lactation.
• Hypokalemia (potassium < 3.5 mmol/l).
• Hyponatremia (sodium <135 mmol/l).
• Severe chronic renal insufficiency (creatinine clearance less than 10 ml/min) or the use of renal replacement therapy or ultrafiltration at any time prior to inclusion in the study.
• Metabolic acidosis (bicarbonate less than 12 mmol/L).
• Severe anemia (Hb <70 g/L).
• Acute renal failure.
• Addison's disease.
• Decompensated diabetes mellitus.
• Emergency conditions (myocardial infarction, pulmonary embolism, acute myocarditis, pericarditis, aortic aneurysm).
• Cirrhosis of the liver with encephalopathy and liver failure.
• Congenital heart defects.
• Malignant neoplasm in the phase of active treatment or terminal form of cancer.
• Hypocorticism.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: a group with the use of acetazolamide; acetazolamide is prescribed at a dose of 250 mg 3 times a day	Drug: Acetazolamide; Acetazolamide is a diuretic with a mild diuretic effect. Inhibits the enzyme carbonic anhydrase in the proximal convoluted tubule of the nephron. Increases urinary excretion of sodium, potassium, bicarbonate ions, does not affect the excretion of chlorine ions; causes an increase in urine pH.; Other Names: diacarb
No Intervention: a group of standart therapy; standart therapy includes main and additional medicine for treatment of chronic heart failure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
decrease of decompensation	achievement of compensation in accordance with the criteria for discontinuation of diuretic therapy.	3 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
an increase of urine volume	an increase in the volume of urine excreted in the first 72 hours of hospitalization (from the moment of randomization)	3 days
Weight loss	a decrease of the weight	10 days
Natriuresis	Natriuresis (evaluation in daily urine)	10 days
Duration of hospitalization	Duration of hospitalization	10 days
Duration of stay in the ICU	Duration of stay in the ICU	10 days
Death from any cause	Death from any cause within 90 days	90 days
Death from cardiovascular diseases	Death from cardiovascular diseases within 90 days	90 days
Death from decompensation of CHF or CHF	Death from decompensation of CHF or CHF within 90 days	90 days
The number of pleural and pericardial punctures	The number of pleural and pericardial punctures performed during the period of hospitalization	10 days
The number of points according to the SHOKS (clinical condition assessment scale) score	0 points - absence of clinical signs of heart failure, I class - less than or equal to 3 points; II class - from 4 to 6 points; III class - from 7 to 9 points; IV class - more than 9 points.	10 days
6-minute walk test	6-minute walk test at discharge from the hospital	10 days

Collaborators and Investigators

• Sponsor: Samara State Medical University
• Investigators: Principal Investigator: Dmitriy Duplyakov, SamSMU

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2023
• Primary Completion (Estimated): August 28, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: March 22, 2023
• First Submitted That Met QC Criteria: April 4, 2023
• First Posted (Actual): April 7, 2023

Study Record Updates

• Last Update Posted (Estimated): November 5, 2024
• Last Update Submitted That Met QC Criteria: November 2, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: acetazolamide; edema syndrome
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Diuretics; Natriuretic Agents; Anticonvulsants; Carbonic Anhydrase Inhibitors; Acetazolamide
• Other Study ID Numbers: 001 (Buy Pharma Ecza Deposu San. Tic. Ltd.)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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