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Diuretic and Natriuretic Effect of High-dose Spironolactone in Patients With Acute Heart Failure (DANAUS-AHF)

Primary Purpose

Heart Failure Acute, Heart Failure; With Decompensation

Status
Unknown status
Phase
Phase 4
Locations
Greece
Study Type
Interventional
Intervention
Spironolactone
Sponsored by
Laikο General Hospital, Athens
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Heart Failure Acute focused on measuring diuretic resistance, spironolactone, cardio-renal syndrome, diuretics, natriuresis, heart failure

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Diagnosis of acute heart failure within the past 8 hours
  • Two of the following: 1. edema, 2. ascites, 3. jugular vein distention, 4. pulmonary congestion
  • NT-proBNP >1,000 pg/ml or >3,000 pg/ml (in the presence of atrial fibrillation)
  • Per os mean daily loop diuretic dose equivalent to 80 mg of furosemide for at least 1 month prior to presentation and at least one of the following: 1. serum urea/serum creatinine > 50 at presentation, 2. serum creatinine increased >0.3 mg/dl compared with previous value (within the last year), 3. serum creatinine > 1.8 mg/dl.

Exclusion Criteria:

  • pregnancy or breast feeding
  • current acute coronary syndrome
  • significant valvular disease
  • pulmonary embolism
  • allergy or intolerance to spironolactone
  • current mechanical circulatory support
  • primary hypertrophic cardiomyopathy, infiltrative cardiomyopathy
  • mean arterial pressure <65mmHg or systolic arterial pressure <90 mmHg at presentation
  • anticipated use of inotropes or vasodilators (other than renal doses of dopamine, i.e. <2.5 μg/kg/min)
  • anticipated need of ultrafiltration
  • exposure to nephrotoxic agents within 3 days of presentation
  • serum potassium> 5 mmol/L
  • per os receipt of spironolactone or eplerenone in a dose > 50 mg daily prior to presentation.

Sites / Locations

  • Laiko General Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

No Intervention

Arm Label

High-dose spironolactone

Standard of care

Arm Description

Participants in this arm will receive high doses of per os spironolactone, defined as doses ≥100 mg daily, on top of standard of care treatment for acute heart failure

Participants in this arm will standard of care treatment for acute heart failure, which may include per os spironolactone at a maximum dose of 50 mg daily

Outcomes

Primary Outcome Measures

Daily urine output
Urine output in liters per 24 hours will be tracked from enrollment to day 5.

Secondary Outcome Measures

Total urine output
Urine output in total liters from enrollment to day 5 will be measured.
Total weight change
Patient weight in kilos will be tracked from enrollment to day 5.
Daily weight change
Patient weight in kilos will be tracked from enrollment to day 5.
Natriuresis on days 1, 3 and 5
Urine sodium will be measured on days 1, 3 and 5
Changes in natriuresis between days 1, 3 and 5
Urine sodium will be measured on days 1, 3 and 5
Changes in NT-proBNP between days 1 and 5
NT-proBNP will be measured on days 1, 3 and 5

Full Information

First Posted
November 1, 2020
Last Updated
November 6, 2020
Sponsor
Laikο General Hospital, Athens
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1. Study Identification

Unique Protocol Identification Number
NCT04618601
Brief Title
Diuretic and Natriuretic Effect of High-dose Spironolactone in Patients With Acute Heart Failure
Acronym
DANAUS-AHF
Official Title
Diuretic and Natriuretic Effect of High-dose Spironolactone in Patients With Acute Heart Failure
Study Type
Interventional

2. Study Status

Record Verification Date
November 2020
Overall Recruitment Status
Unknown status
Study Start Date
October 20, 2020 (Actual)
Primary Completion Date
December 20, 2021 (Anticipated)
Study Completion Date
March 1, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Laikο General Hospital, Athens

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a prospective, single-center, open-label and randomized trial for evaluation of the effect of a 5-day administration of high doses of spironolactone (≥100mg daily) on diuresis, natriuresis, weight loss and levels of NT-proBNP in hospitalized patients with acute decompensated heart failure (ADHF). Mineralocorticoid receptor antagonists (MRAs) are recommended as standard of care (SOC) in management of heart failure (HF) patients. However, recommended doses of MRAs (up to 50mg daily) have any impact on signs and symptoms of volume overload. Therefore, the proposed study will aim to show the impact of high doses of spironolactone to improve diuresis, natriuresis, weight loss and levels of NT-proBNP in hospitalized patients with ADHF.
Detailed Description
Congestion represents a hallmark feature of ADHF, which is present in more than 90% of patients hospitalized for this diagnosis. Intravenous loop diuretics are the mainstay of treatment. Nonetheless, nearly half of the patients who are hospitalized for AdHF continue to have residual symptoms and sign of congestion at time of discharge. Various pharmacological and non-pharmacological interventions have been proposed over the past years as potential means for relieving congestion in hospitalized ADHF patients. However, their efficacy has not been shown. Given that hyperaldosteronism is a key feature in HF, the hypothesis that administration of high doses of spironolactone can potentiate the natriuretic effects of loop diuretics and relieve congestion in the setting of ADHF has been raised. According to the most recent guidelines spironolactone can be considered in combination with loop diuretic in patients with resistant edema or insufficient symptomatic response. However, spironolactone at a dose of 100 mg daily has failed to increase diuresis in patients with ADHF. The present study will assess the effect of high per os doses of spironolactone (≥100mg) on top of SOC treatment compared with SOC treatment alone on diuresis, natriuresis, weight loss and levels of NT-proBNP in hospitalized patients with ADHF.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure Acute, Heart Failure; With Decompensation
Keywords
diuretic resistance, spironolactone, cardio-renal syndrome, diuretics, natriuresis, heart failure

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
High-dose spironolactone
Arm Type
Active Comparator
Arm Description
Participants in this arm will receive high doses of per os spironolactone, defined as doses ≥100 mg daily, on top of standard of care treatment for acute heart failure
Arm Title
Standard of care
Arm Type
No Intervention
Arm Description
Participants in this arm will standard of care treatment for acute heart failure, which may include per os spironolactone at a maximum dose of 50 mg daily
Intervention Type
Drug
Intervention Name(s)
Spironolactone
Other Intervention Name(s)
Aldactone
Intervention Description
Patients randomized to the high-dose spironolactone group will receive oral spironolactone (≥100 mg) on top of standard of care treatment for acute heart failure immediately after randomization and in the afternoon of each subsequent day unless the serum potassium level is >5 mmol/L. The exact dose will be determined based on a pre-specified algorithm provided.
Primary Outcome Measure Information:
Title
Daily urine output
Description
Urine output in liters per 24 hours will be tracked from enrollment to day 5.
Time Frame
5 days
Secondary Outcome Measure Information:
Title
Total urine output
Description
Urine output in total liters from enrollment to day 5 will be measured.
Time Frame
5 days
Title
Total weight change
Description
Patient weight in kilos will be tracked from enrollment to day 5.
Time Frame
5 days
Title
Daily weight change
Description
Patient weight in kilos will be tracked from enrollment to day 5.
Time Frame
5 days
Title
Natriuresis on days 1, 3 and 5
Description
Urine sodium will be measured on days 1, 3 and 5
Time Frame
5 days
Title
Changes in natriuresis between days 1, 3 and 5
Description
Urine sodium will be measured on days 1, 3 and 5
Time Frame
5 days
Title
Changes in NT-proBNP between days 1 and 5
Description
NT-proBNP will be measured on days 1, 3 and 5
Time Frame
5 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diagnosis of acute heart failure within the past 8 hours Two of the following: 1. edema, 2. ascites, 3. jugular vein distention, 4. pulmonary congestion NT-proBNP >1,000 pg/ml or >3,000 pg/ml (in the presence of atrial fibrillation) Per os mean daily loop diuretic dose equivalent to 80 mg of furosemide for at least 1 month prior to presentation and at least one of the following: 1. serum urea/serum creatinine > 50 at presentation, 2. serum creatinine increased >0.3 mg/dl compared with previous value (within the last year), 3. serum creatinine > 1.8 mg/dl. Exclusion Criteria: pregnancy or breast feeding current acute coronary syndrome significant valvular disease pulmonary embolism allergy or intolerance to spironolactone current mechanical circulatory support primary hypertrophic cardiomyopathy, infiltrative cardiomyopathy mean arterial pressure <65mmHg or systolic arterial pressure <90 mmHg at presentation anticipated use of inotropes or vasodilators (other than renal doses of dopamine, i.e. <2.5 μg/kg/min) anticipated need of ultrafiltration exposure to nephrotoxic agents within 3 days of presentation serum potassium> 5 mmol/L per os receipt of spironolactone or eplerenone in a dose > 50 mg daily prior to presentation.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John Barbetseas, MD
Organizational Affiliation
Laikon General Hospital
Official's Role
Study Chair
Facility Information:
Facility Name
Laiko General Hospital
City
Athens
State/Province
Attiki
ZIP/Postal Code
11527
Country
Greece

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
The individual participant data of the study will be shared on reasonable request to the principle investigator
Citations:
PubMed Identifier
29971596
Citation
Kapelios CJ, Bonou M, Vogiatzi P, Tzanis G, Mantzouratou P, Lund LH, Barbetseas J. Association Between High-Dose Spironolactone and Decongestion in Patients with Acute Heart Failure: An Observational Retrospective Study. Am J Cardiovasc Drugs. 2018 Oct;18(5):415-422. doi: 10.1007/s40256-018-0290-3.
Results Reference
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Diuretic and Natriuretic Effect of High-dose Spironolactone in Patients With Acute Heart Failure

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