Aldosterone BloCkade for Health Improvement EValuation in End-stage Renal Disease

Phase 3

Completed

• Conditions: Endstage Renal Disease
• Interventions: Drug: Placebo Oral Tablet; Drug: Spironolactone 25Mg Tablet

• Registration Number: NCT03020303
• Lead Sponsor: Population Health Research Institute

Brief Summary

Individuals receiving dialysis are at risk of heart failure and heart related death. There is an urgent need for treatments that reduce the risk of these problems in patients that require dialysis.

Spironolactone is a pill used to prevent heart failure and related deaths in patients that do not require dialysis. It works by blocking a hormone (aldosterone) in your body that causes high blood pressure and can damage the heart. Although spironolactone is very effective in patients that do not require dialysis, we do not know if spironolactone is effective in dialysis patients. Our research will help determine if spironolactone reduces heart failure and heart related deaths in dialysis patients.

The purpose of this study is to determine if spironolactone reduces death or hospitalization for heart failure and is well tolerated in patients that require dialysis.

Detailed Description

Globally, over 2 million people receive dialysis for end-stage renal disease (ESRD) and 650,000 new patients start dialysis each year. Furthermore, the number of patients receiving dialysis is increasing as access to dialysis in the developing world improves and the prevalence of diabetes and vascular disease rises. Despite technical advances in dialysis, the outcomes for patients with ESRD are poor. Patients have frequent hospitalizations, poor health related quality of life and strikingly, high mortality rates.

The most common cause of death in patients receiving dialysis is cardiovascular disease, accounting for \>40% of all deaths. Observational studies suggest a causal pathway to cardiovascular death that includes progressive ventricular hypertrophy and dilatation as well as accelerated atherosclerosis. These changes result in myocardial ischemia and cardiac fibrosis that, in turn, lead to heart failure, arrhythmias and cardiac arrest. Strongly implicated in this pathophysiology is aldosterone. Mineralocorticoid receptor antagonists (MRAs) in non-ESRD patients, prevent cardiovascular deaths and small randomized controlled trials of MRAs in ESRD suggests they may reduce death and may be safe.

Spironolactone is the most commonly used MRA worldwide. We will conduct a multicentre randomized controlled trial (RCT) to determine if spironolactone reduces cardiac mortality and hospitalizations for heart failure in patients treated with dialysis. This trial is called the Aldosterone bloCkade for Health Improvement EValuation in End-stage renal disease (ACHIEVE).

Study Timeline

• Study First Submitted: 2017-01-11
• Study First Submitted QC: 2017-01-11
• Study First Posted: 2017-01-13
• Study Start: 2017-07-07
• Status Verified: 2025-03
• Primary Completion: 2025-03-14
• Study Completion: 2025-03-14
• Last Update Submitted: 2025-03-17
• Last Update Posted: 2025-03-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 2538

Inclusion Criteria

1. Age

   1. ≥45 years or
   2. ≥18 with a history of diabetes

2. On dialysis ≥ 90 days

3. On either

   1. Hemodialysis prescribed at least 2 treatments per week or
   2. Peritoneal dialysis prescribed with at least 1 exchange daily

4. Provides informed consent

Exclusion Criteria

1. Hyperkalemia

   1. Serum potassium >5.8 mmol/L in the 6 weeks prior to enrollment or
   2. Serum potassium >6.0 mmol/L during active run-in

2. Currently taking and unable to withdraw a mineralocorticoid receptor antagonist (i.e. spironolactone or eplerenone).

3. Known sensitivity or allergy to spironolactone

4. Current or planned pregnancy or breastfeeding

5. Scheduled living related donor renal transplant

6. Life expectancy < 6 months in the opinion of a treating nephrologist.

7. Enrolled in another interventional trial testing a mineralocorticoid receptor antagonist or drug that has a known or likely interaction with spironolactone.

8. Treating physician believes either spironolactone is either absolutely indicated or absolutely contra-indicated

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo Oral Tablet	Placebo Oral Tablet	A tablet with no active medication that will be an exact match of the active spironolactone in taste and appearance
Spironolactone 25 MG Tablet	Spironolactone 25Mg Tablet	25 mg of active spironolactone in tablet form

Primary Outcome Measures

Name	Time	Method
CV Death or Hospitalization for Heart Failure	up to 5 years

Secondary Outcome Measures

Name	Time	Method
Cause specific death	up to 5 years
Hospitalization for Heart Failure	up to 5 years
All-cause death	up to 5 years
All-cause Hospitalization	up to 5 years
Hospitalization for hyperkalemia	up to 5 years

Trial Locations

Locations (141)

Canberra Hospital; 🇦🇺 Garran, Australian Capital Territory, Australia

Concord Repatriation General Hospital; 🇦🇺 Concord, New South Wales, Australia

Northern Beaches Hospital; 🇦🇺 Frenchs Forest, New South Wales, Australia

Royal North Shore Hospital; 🇦🇺 Wahroonga, New South Wales, Australia

Sydney Adventist Hospital; 🇦🇺 Wahroonga, New South Wales, Australia

Sunshine Coast University Hospital; 🇦🇺 Birtinya, Queensland, Australia

Royal Brisbane Women&#39;s Hospital; 🇦🇺 Herston, Queensland, Australia

Princess Alexandra Hospital; 🇦🇺 Woolloongabba, Queensland, Australia

Monash Health; 🇦🇺 Clayton, Victoria, Australia

Western Health - Sunshine Hospital; 🇦🇺 Saint Albans, Victoria, Australia

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