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)

City Hospital; 🇬🇧 Nottingham, United Kingdom

Salford Royal Hospital; 🇬🇧 Salford, United Kingdom

Tianjin Fifth Central Hospital; 🇨🇳 Tianjin, China

Santa Casa de Misericordia de Ponta Grossa; 🇧🇷 Ponta Grossa, Brazil

Hospital Sultanah Aminah, Johor Bahru; 🇲🇾 Johor Bahru, Johor, Malaysia

Hospital Pakar Sultanah Fatimah; 🇲🇾 Muar, Johor, Malaysia

Hospital Taiping; 🇲🇾 Taiping, Perak, Malaysia

Hospital Pulau Pinang; 🇲🇾 George Town, Pulau Pinang, Malaysia

Hospital Kajang; 🇲🇾 Kajang, Selangor, Malaysia

Hospital Tengku Ampuan Rahimah Klang; 🇲🇾 Klang, Selangor, Malaysia

Hospital Kuala Lumpur; 🇲🇾 Kuala Lumpur, Malaysia

University Malaya Medical Centre (UMMC); 🇲🇾 Kuala Lumpur, Malaysia

Hospital Sultanah Nur Zahirah Kuala Terengganu; 🇲🇾 Kuala Terengganu, Malaysia

Hospital Tengku Ampuan Afzan, Kuantan; 🇲🇾 Kuantan, Malaysia

Hospital Tuanku Jaafar, Seremban; 🇲🇾 Seremban, Malaysia

Hospital Ampang; 🇲🇾 Setapak, Malaysia

Royal Stoke University Hospital; 🇬🇧 Stoke-on-Trent, United Kingdom

Beijing Miyun District Hospital; 🇨🇳 Beijing, China

Faw General Hospital of Jilin Province; 🇨🇳 Changchun, China

The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture; 🇨🇳 Enshi, China

Huai'an First Peoples Hospital; 🇨🇳 Huai'an, China

The First Hospital of Kunming; 🇨🇳 Kunming, China

Gansu Baoshihua Hospital; 🇨🇳 Lanzhou, China

Yichuan County Traditional Chinese Medicine Hospital; 🇨🇳 Luoyang, China

The First Affiliated Hospital of Baotou Medical College; 🇨🇳 Baotou, China

Government Rajaji Hospital, Madurai; 🇮🇳 Madurai, India

Father Muller Medical College; 🇮🇳 Mangalore, India

Seven Star Hospital; 🇮🇳 Nagpur, India

Beijing Tongren Hospital, Capital Medical University; 🇨🇳 Beijing, China

Shuyang County Hospital of Traditional Chinese Medicine; 🇨🇳 Suqian, China

Sihong County Fenjinting Hospital; 🇨🇳 Suqian, China

Emergency General Hospital; 🇨🇳 Beijing, China

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

Santa Casa de Misericordia de Belo Horizonte; 🇧🇷 Santa Efigênia, Belo Horizonte, Brazil

Medical School of Botucatu of the Paulista State University - UNESP; 🇧🇷 Rubiao Junior, Botucatu, Brazil

Fundacao Pro-Rim; 🇧🇷 Boa Vista, Joinville, Brazil

Felicio Rocho Foundation - Hospital Felicio Rocho; 🇧🇷 Belo Horizonte, Minas Gerais, Brazil

Fundacao Hospitalar Sao Francisco de Assis; 🇧🇷 Belo Horizonte, Minas Gerais, Brazil

Servico Ubaense de Nefrologia Ltda; 🇧🇷 Uba, Minas Gerais, Brazil

Sociedade Hospitalar Angelina Caron; 🇧🇷 Campina Grande Do Sul, Parana, Brazil

Instituto Pro Renal Brazil; 🇧🇷 Curitiba, Parana, Brazil

Irmandade da Santa Casa de Misericordia de Porto Alegre -ISCMPA; 🇧🇷 Bairro Santa Teresa, Porto Alegre, Brazil

Hospital de Clinicas de Porto Alegre; 🇧🇷 Porto Alegre, Rio Grande do Sul, Brazil

Hospital Arquidiocesano Consul Carlos Reneaux; 🇧🇷 Brusque, Santa Catarina, Brazil

Praxis Pesquisa Medica S/S; 🇧🇷 Santo André, Sao Paulo, Brazil

Santa Casa de Misericordia de Votuporanga; 🇧🇷 Votuporanga, Sao Paulo, Brazil

PROCARDIO Clinica Cardiologica; 🇧🇷 Blumenau, South Carolina, Brazil

Hospital Alemao Oswaldo Cruz; 🇧🇷 Bela Vista, Brazil

Foothills Hospital; 🇨🇦 Calgary, Alberta, Canada

University of Alberta; 🇨🇦 Edmonton, Alberta, Canada

Royal Inland Hospital; 🇨🇦 Kamloops, British Colombia, Canada

Kelowna General Hospital; 🇨🇦 Kelowna, British Colombia, Canada

St. Pauls Hospital; 🇨🇦 Vancouver, British Colombia, Canada

Penticton Regional Hospital; 🇨🇦 Penticton, British Columbia, Canada

Queen Elizabeth II Health Science Centre; 🇨🇦 Halifax, Nova Scotia, Canada

Cape Breton Regional Hospital; 🇨🇦 Sydney, Nova Scotia, Canada

St. Joseph's Healthcare; 🇨🇦 Hamilton, Ontario, Canada

Queens University at Kingston General Hospital, Division of Nephrology; 🇨🇦 Kingston, Ontario, Canada

Victoria Hospital; 🇨🇦 London, Ontario, Canada

Ottawa Hospital Research Institute; 🇨🇦 Ottawa, Ontario, Canada

Health Sciences North Research Institute; 🇨🇦 Sudbury, Ontario, Canada

St. Michael's Hospital; 🇨🇦 Toronto, Ontario, Canada

St. Josephs, Toronto; 🇨🇦 Toronto, Ontario, Canada

Humber River Health; 🇨🇦 Toronto, Ontario, Canada

CIUSSS Hopital Maisonneuve- Rosemont; 🇨🇦 Montreal, Quebec, Canada

Hopital du Sacre-Coeur de Montreal; 🇨🇦 Montreal, Quebec, Canada

The Sir Mortimer B. Davis Jewish General Hospital; 🇨🇦 Montreal, Quebec, Canada

Centre Hospitalier de l&#39;Universite de Montreal (CHUM); 🇨🇦 Montréal, Quebec, Canada

CHU de Quebec L'Hotel-Dieu de Quebec; 🇨🇦 Québec, Quebec, Canada

Peking University First Hospital; 🇨🇳 Beijing, Beijing, China

Peking University Peoples Hospital; 🇨🇳 Beijing, Beijing, China

General Hospital of Ningxia Medical University; 🇨🇳 Yinchuan, Ningxia, China

Shanghai Tongji Hospital; 🇨🇳 Shanghai, China

Shanxi Provincial Peoples Hospital; 🇨🇳 Shanxi, China

Tianjin Third Central Hospital; 🇨🇳 Tianjin, China

Tongiao City Hospital; 🇨🇳 Tongliao, China

Xinxiang First Peoples Hospital; 🇨🇳 Xinxiang, China

General Hospital of Xuzhou Mining Group; 🇨🇳 Xuzhou, China

Peoples Hospital of Yuxi City; 🇨🇳 Yuxi, China

Peoples Hospital of Zhongwei; 🇨🇳 Zhongwei, China

Clinefnorte CIA Ltda; 🇪🇨 Quito, Pichincha, Ecuador

Nefromedic SA; 🇪🇨 Quito, Pichincha, Ecuador

Madras Medical College Chennai; 🇮🇳 Park Town, Chennai, India

Narayana Hrudayalaya Limited; 🇮🇳 Bangalore, Karnataka, India

Fortis Hospitals; 🇮🇳 Bengaluru, Karnataka, India

K S Hegde Medical Academy; 🇮🇳 Mangaluru, Karnataka, India

Nanjappa Hospitals Shimoga; 🇮🇳 Shimoga, Karnataka, India

AsterMedCity; 🇮🇳 Cochin, Kerala, India

Caritas Hospital; 🇮🇳 Kottayam, Kerala, India

AIMS Hospital Mumbai; 🇮🇳 Dombivli, Maharashtra, India

National Health and Education Society; 🇮🇳 Mumbai, Maharashtra, India

Ashirwad Hospital Mumbai; 🇮🇳 Mumbai, Maharashtra, India

Dhadiwal Hospital; 🇮🇳 Nashik, Maharashtra, India

ACE Hospital Une; 🇮🇳 Pune, Maharashtra, India

Aditya Birla Hospital; 🇮🇳 Pune, Maharashtra, India

Vijaya Hospital; 🇮🇳 Chennai, Tamil Nadu, India

Apollo Hospitals; 🇮🇳 Chennai, Tamil Nadu, India

Nizams Institute of Medical Sciences; 🇮🇳 Hyderabad, Telangana, India

Osmania General Hospital; 🇮🇳 Hyderabad, Telegana, India

North Shore Hospital; 🇳🇿 Takapuna, Auckland, New Zealand

Waikato Hospital; 🇳🇿 Hamilton, Waikato, New Zealand

Dunedin Hospital; 🇳🇿 Dunedin, New Zealand

Hawkes Bay Hospital; 🇳🇿 Hastings, New Zealand

Palmerston North Hospital; 🇳🇿 Palmerston North, New Zealand

Whangarei Hospital; 🇳🇿 Whangarei, New Zealand

Philippines General Hospital; 🇵🇭 Ermita, Manila, Philippines

National Kidney and Transplant Institute; 🇵🇭 Quezon City, Manila, Philippines

Hacettepe University Hospitals Hemodialysis Center; 🇹🇷 Ankara, Turkey

Osmangazi University; 🇹🇷 Eskişehir, Turkey

Memorial Service Hospital; 🇹🇷 Istanbul, Turkey

Ulster Hospital; 🇬🇧 Dundonald, Belfast, United Kingdom

Daisy Hill Hospital; 🇬🇧 Newry, Down, United Kingdom

East Kent Canterbury Hospital; 🇬🇧 Canterbury, Kent, United Kingdom

Churchill Hospital; 🇬🇧 Headington, Oxford, United Kingdom

Aberdeen Royal Infirmary; 🇬🇧 Aberdeen, United Kingdom

Belfast City Hospital; 🇬🇧 Belfast, United Kingdom

Birmingham Hospitals; 🇬🇧 Birmingham, United Kingdom

Southmead Hospital; 🇬🇧 Bristol, United Kingdom

University Hospital of Whales Health Park; 🇬🇧 Cardiff, United Kingdom

Epsom St. Helier; 🇬🇧 Carshalton, United Kingdom

Royal Derby Hospital; 🇬🇧 Derby, United Kingdom

Ninewells Hospital; 🇬🇧 Dundee, United Kingdom

Queen Elizabeth University Hospital; 🇬🇧 Glasgow, United Kingdom

Leicester General Hospital; 🇬🇧 Leicester, United Kingdom

Liverpool University Hospitals; 🇬🇧 Liverpool, United Kingdom

The Royal London Hospital; 🇬🇧 London, United Kingdom

Kings College Hospital; 🇬🇧 London, United Kingdom

South Tees James Cook Hospital; 🇬🇧 Middlesbrough, United Kingdom

Canimel Center; 🇺🇾 Melo, Cerro Largo, Uruguay

SEDIC Center; 🇺🇾 Montevideo, Uruguay

Cedina Center; 🇺🇾 Montevideo, Uruguay

Centro de Asistencia del Sindicato Medico del Uruguay-Institucion de Asistencia medica Privada (CASMU-IAMPP); 🇺🇾 Montevideo, Uruguay