Heart Failure AcutePhase 4DANAUS-AHFNCT04618601
Diuretic and Natriuretic Effect of High-dose Spironolactone in Patients With Acute Heart Failure
A Phase 4 study testing Spironolactone in people with Heart Failure Acute and Heart Failure; With Decompensation, run by Laikο General Hospital, Athens at 1 site in Greece.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure Acute, Heart Failure; With Decompensation
- What is being tested?
- Spironolactone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteGreece
- Study dates
- 20 Oct 2020to 1 Mar 2022
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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
- 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.
Who cannot join
- pregnancy or breast feeding
- current acute coronary syndrome
- significant valvular disease
- pulmonary embolism
- allergy or intolerance to spironolactone
- current mechanical circulatory support
Show all 13Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Being tested
- Spironolactone
- Keywords
- diuretic resistance, spironolactone, cardio-renal syndrome, diuretics, natriuresis, heart failure
- Medical subject headings
- Heart Failure, Cardio-Renal Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SpironolactoneDrug
Also called Aldactone
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.
| Study group | Role | What they receive |
|---|---|---|
| High-dose spironolactone | Active comparator | 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 Receives: Drug: Spironolactone |
| Standard of care | No intervention | 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Daily urine output
Urine output in liters per 24 hours will be tracked from enrollment to day 5.
Measured: 5 days
Secondary outcomes (6)
Total urine output
Urine output in total liters from enrollment to day 5 will be measured.
Measured: 5 days
Total weight change
Patient weight in kilos will be tracked from enrollment to day 5.
Measured: 5 days
Daily weight change
Patient weight in kilos will be tracked from enrollment to day 5.
Measured: 5 days
Natriuresis on days 1, 3 and 5
Urine sodium will be measured on days 1, 3 and 5
Measured: 5 days
Changes in natriuresis between days 1, 3 and 5
Urine sodium will be measured on days 1, 3 and 5
Measured: 5 days
Changes in NT-proBNP between days 1 and 5
NT-proBNP will be measured on days 1, 3 and 5
Measured: 5 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2020
- Study start20 Oct 2020
- Primary completion20 Dec 2021 (estimated)
- Study completion1 Mar 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Laikο General Hospital, Athens
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Chris Kapelios, Laikο General Hospital, Athens
- Investigators
- John Barbetseas, MD, Study chair, Laikon General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04618601
- Sponsor's protocol ID
- 15606
- Acronym
- DANAUS-AHF
- Status last verified
- Nov 2020
- First submitted
- 1 Nov 2020
- Last updated
- 10 Nov 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: The individual participant data of the study will be shared on reasonable request to the principle investigator
Publications
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.
PubMed 29971596
Study at a glance
From the registry record, last updated by the sponsor on 10 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Diuretic and Natriuretic Effect of High-dose Spironolactone in Patients With Acute Heart Failure
- ClinicalTrials.gov ID
- NCT04618601
- Acronym / sponsor ID
- DANAUS-AHF / 15606
- Keywords
- diuretic resistance, spironolactone, cardio-renal syndrome, diuretics, natriuresis, heart failure
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Laikο General Hospital, AthensUniversity, hospital or other
- Study start
- 20 Oct 2020 (actual)
- Primary completion
- 20 Dec 2021 (estimated)
- Study completion
- 1 Mar 2022 (estimated)
- First posted
- 6 Nov 2020 (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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| High-dose spironolactone | Active comparator | Drug: SpironolactoneParticipants 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 |
| Standard of care | No intervention | –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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (13 listed)
- pregnancy or breast feeding
- current acute coronary syndrome
- significant valvular disease
- pulmonary embolism
- allergy or intolerance to spironolactone
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 |
|---|---|---|
| SpironolactoneAlso: AldactonePatients 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. | Drug | High-dose spironolactone |
Primary outcome
Daily urine output
Time frame: 5 days
Urine output in liters per 24 hours will be tracked from enrollment to day 5.
6 secondary outcomes
Total urine output
Time frame: 5 days
Total weight change
Time frame: 5 days
Daily weight change
Time frame: 5 days
Natriuresis on days 1, 3 and 5
Time frame: 5 days
Changes in natriuresis between days 1, 3 and 5
Time frame: 5 days
Changes in NT-proBNP between days 1 and 5
Time frame: 5 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Nov 2020.
- Background: PubMed 29971596Kapelios 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.
- Individual participant dataSharing planned: No. The individual participant data of the study will be shared on reasonable request to the principle investigator
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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. This study is not recruiting at the moment.
John Barbetseas, MD study chair
Laikon General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Spironolactone in people with Heart Failure Acute and Heart Failure; With Decompensation, run by Laikο General Hospital, Athens at 1 site in Greece.
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 4 inclusion and 13 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: status not confirmed, as of the sponsor's last update on 10 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Greece. Whether a site is taking part right now should be confirmed with that site. See every site.
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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Daily urine output (time frame: 5 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 NCT04618601, which also lists 1 linked publication.
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 10 Nov 2020.