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

Conditions

Endstage Renal Disease

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).

Walsh M, Collister D, Gallagher M, Mark PB, de Zoysa JR, Tyrwhitt J, Tennankore K, Reis G, Xavier D, Liu WJ, Zuo L, Wang AY, Félix C, Sola L, Arici M, Villanueva R, Jha V, Précoma D, Rabbat CG, Alavudeen SS, Faruqui AR, López-Flecher M, Pyne L, Wald R, Yuan F, Balasubramanian K, Lee SF, Kuptsova A, Christou C, Devereaux PJ, ACHIEVE Investigators.

2025-08-0111 citations

10.1016/s0140-6736(25)01198-5

The Aldosterone Blockade for Health Improvement Evaluation in End-Stage Renal Disease (ACHIEVE) Trial: Rationale and Clinical Research Protocol

Michael Walsh, David Collister, Martin Gallagher, Patrick B. Mark, Janak de Zoysa et al. (25 authors)

Canadian Journal of Kidney Health and Disease2025-06-031 citations

10.1177/20543581251348187

Three week compared to seven week run-in period length and the assessment of pre-randomization adherence: A study within a trial.

Collister D, Mbuagbaw L, Guyatt G, Devereaux PJ, Tennankore KK, Reis G, Sola L, Xavier D, Jha V, Gallagher M, Dans AL, Liu W, de Zoysa J, Félix C, Mark PB, Li Z, Tyrwhitt J, Wilkinson J, Sheridan P, Yuan F, Walsh M, ACHIEVE investigators.

2021-06-051 citations

10.1016/j.cct.2021.106466

The safety of mineralocorticoid antagonists in maintenance hemodialysis patients: two steps forward.

Rossignol P, Frimat L, Zannad F.

2019-04-0121 citations

10.1016/j.kint.2018.12.006

Interventions

DRUGSpironolactone 25Mg Tablet

Randomized participants will receive a study supply of spironolactone 25 mg tablets. They will be instructed to take 1 tablet daily.

DRUGPlacebo Oral Tablet

Randomized participants will receive a study supply of placebo tablets with no active medical ingredients. They will be instructed to take 1 tablet daily.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

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

Design outcomes

Primary

Measure	Time frame
CV Death or Hospitalization for Heart Failure	up to 5 years

Secondary

Measure	Time frame
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

Countries

Australia, Brazil, Canada, China, Ecuador, India, Malaysia, New Zealand, Philippines, Turkey (Türkiye), United Kingdom, Uruguay

Contacts

PRINCIPAL_INVESTIGATORMichael Walsh, MD, PhD

McMaster University

STUDY_CHAIRPJ Devereaux, MD, PhD