Spironolactone for Heart Failure

Overseen By Veena Rao

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Yale University

Must not be taking: Potassium sparing diuretics

Disqualifiers: Uncontrolled hypertension, Severe bladder dysfunction, Pregnancy, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 14

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how spironolactone, a medication, can aid people with heart failure by assessing its effectiveness when aldosterone, a hormone affecting heart health, is involved. Participants will receive various combinations of spironolactone, a placebo, and aldosterone to evaluate their impact on heart health. It suits individuals with stable heart failure who have maintained steady medications without recent flare-ups. As a Phase 4 trial, this research aims to understand how the already FDA-approved and effective treatment benefits more patients.

Will I have to stop taking my current medications?

The trial requires that your heart failure medications remain stable, meaning you should not change them during the 8-week study period.

What is the safety track record for spironolactone?

Research has shown that spironolactone is usually well-tolerated by people with heart failure. One study found that taking a high dose of spironolactone along with regular treatment for a short time was generally safe, with most participants not experiencing major problems. However, another study discovered that in everyday use, people experienced more side effects than in controlled trials. This suggests that while spironolactone can be safe, some individuals might encounter more side effects outside a study setting. Additionally, spironolactone has been linked to certain safety concerns, so monitoring for side effects is important. Overall, spironolactone is approved for heart failure and is generally safe when used correctly, but like any medication, it can have side effects. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Spironolactone is unique because it offers a different approach to treating heart failure compared to standard options like ACE inhibitors, beta-blockers, and diuretics. Unlike most heart failure treatments that primarily reduce blood pressure or improve heart pumping, spironolactone works by blocking the effects of aldosterone, a hormone that can contribute to heart damage. This mechanism helps reduce fluid retention and prevent further heart stress, which could lead to better outcomes for patients. Researchers are excited about spironolactone because it has the potential to be more effective in protecting the heart from long-term damage and improving quality of life for those with heart failure.

What is the effectiveness track record for spironolactone in treating heart failure?

Research has shown that spironolactone effectively treats heart failure. In this trial, participants will receive different combinations of treatments, including spironolactone, to evaluate its effects. Studies have found that spironolactone benefits patients with heart failure, especially those whose hearts struggle to pump blood. One study discovered that spironolactone significantly reduced the risk of heart problems, such as heart attacks or strokes. For patients whose hearts pump normally but still experience heart failure, spironolactone helped them live longer, regardless of the cause of death. Overall, spironolactone shows promise in managing heart failure by improving heart function and lowering the risk of serious heart issues. ^{1 2 6 7 8}

Who Is on the Research Team?

Jeffrey Testani, MD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for adults with stable, chronic heart failure (NYHA class I or II), normal blood pressure and potassium levels, and kidney function above a certain threshold. They must not have had recent heart failure worsening, be on steady heart failure meds without changes expected during the study, and women of childbearing age should use effective contraception.

Inclusion Criteria

My blood pressure is above 90 mmHg without MRA medication, or above 80 mmHg with it.

I have not had worsening heart failure in the last 60 days.

Serum potassium ≤5.0 meq/L and ≥3.5 meq/L

Exclusion Criteria

My blood pressure is not higher than 160 mmHg.

History of severe hyperkalemia (K>6.0 meq/l)

I am taking more than 50mg of spironolactone or a similar medication.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo a crossover study with IV infusions and oral medications, including placebo and spironolactone, over multiple periods

8 weeks

Visits on Day 14, 29, 44, 59

Washout

Two-week washout period between crossover phases to allow for steady state blood levels or complete washout of spironolactone

2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Spironolactone

Trial Overview

The study aims to understand the biology behind current anti-aldosterone therapies by comparing Spironolactone (a standard treatment) against a placebo while monitoring aldosterone levels in participants with heart failure.

How Is the Trial Designed?

Group I: Placebo/Sprironolactone Active Control 2 Interventions

This study will employ a randomized placebo-controlled, double-blind, double-dummy, crossover design testing combinations 1\) IV Vehicle infusion plus oral placebo pill 2) IV Vehicle infusion plus oral 25mg spironolactone 3) IV Aldosterone infusion plus oral placebo pill 4) IV Aldosterone infusion plus oral 25 mg spironolactone on Day 14, 29, 44, 59.

Group II: placebo/aldosterone Active Control 2 Interventions

This study will employ a randomized placebo-controlled, double-blind, double-dummy, crossover design testing combinations 1\) IV Vehicle infusion plus oral placebo pill 2) IV Vehicle infusion plus oral 25mg spironolactone 3) IV Aldosterone infusion plus oral placebo pill 4) IV Aldosterone infusion plus oral 25 mg spironolactone on Day 14, 29, 44, 59.

Group III: aldosterone/spironolactone Active Control 2 Interventions

This study will employ a randomized placebo-controlled, double-blind, double-dummy, crossover design testing combinations 1\) IV Vehicle infusion plus oral placebo pill 2) IV Vehicle infusion plus oral 25mg spironolactone 3) IV Aldosterone infusion plus oral placebo pill 4) IV Aldosterone infusion plus oral 25 mg spironolactone on Day 14, 29, 44, 59.

Group IV: Placebo/placebo Placebo Group 1 Intervention

This study will employ a randomized placebo-controlled, double-blind, double-dummy, crossover design testing combinations 1\) IV Vehicle infusion plus oral placebo pill 2) IV Vehicle infusion plus oral 25mg spironolactone 3) IV Aldosterone infusion plus oral placebo pill 4) IV Aldosterone infusion plus oral 25 mg spironolactone on Day 14, 29, 44, 59.

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Boehringer Ingelheim

Industry Sponsor

Trials

2,566

Recruited

16,150,000+

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7083406/

Spironolactone use is associated with improved outcomes ...

Spironolactone has been shown to improve outcomes in patients with heart failure (HF) with reduced ejection fraction (EF). We investigated whether the ...

2.

ahajournals.org

ahajournals.org/doi/10.1161/JAHA.120.018827

Spironolactone Use and Improved Outcomes in Patients ...

In conclusion, the results of our study demonstrated that spironolactone use led to a decreased risk of composite cardiovascular events, all‐ ...

3.

cfrjournal.com

cfrjournal.com/articles/cardiovascular-benefits-spironolactone-heart-failure-mildly-reduced-or-preserved-ejection?language_content_entity=en

Spironolactone's Cardiovascular Benefits in Heart Failure

Hierarchical analysis of the primary composite outcome revealed a significant higher probability of win (28.3%) compared to loss (23.1%) in the ...

4.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa1313731

Spironolactone for Heart Failure with Preserved Ejection ...

With a mean follow-up of 3.3 years, the primary outcome occurred in 320 of 1722 patients in the spironolactone group (18.6%) and 351 of 1723 ...

5.

thecardiologyadvisor.com

thecardiologyadvisor.com/news/spironolactone-https-www-empr-com-generic-drug-spironolactone/

Real-World Data Suggests Spironolactone Decreases ...

A study has found that spironolactone decreases all-cause mortality in patients with heart failure with preserved ejection fraction.

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/28700781/

Efficacy and Safety of Spironolactone in Acute Heart Failure

Adding treatment with high-dose spironolactone to usual care for patients with AHF for 96 hours was well tolerated but did not improve the primary or secondary ...

7.

sciencedirect.com

sciencedirect.com/science/article/pii/S0735109702026943

Clinical study: heart failure Complications of inappropriate ...

Our study reveals that complications with spironolactone use in patients with HF are greater in clinical practice than reported in a rigorous trial.

8.

jacc.org

jacc.org/doi/10.1016/j.jchf.2019.08.019

Influence of Age on Efficacy and Safety of Spironolactone ...

However, spironolactone was associated with an increased risk of the safety endpoint (hazard ratio: 2.54; 95% confidence interval: 1.91 to 3.37; ...