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

Endstage Renal Disease Clinical Trial

— ACHIEVE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03020303
• Other study ID #: ACHIEVE
• Status: Recruiting
• Phase: Phase 3
• Start date: July 7, 2017
• Est. completion date: January 2025

Study information

• Verified date: February 2023
• Source: Population Health Research Institute
• Contact: Jessica Tyrwhitt, B.A.
• Phone: 9055274322
• Email: jessica.tyrwhitt[@]phri.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2750
• Est. completion date: January 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Endstage Renal Disease
• Kidney Diseases
• Kidney Failure, Chronic

Intervention

Drug:
• Spironolactone 25Mg Tablet
Randomized participants will receive a study supply of spironolactone 25 mg tablets. They will be instructed to take 1 tablet daily.
• Placebo 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.

Locations

Country	Name	City	State
Australia	Sunshine Coast University Hospital	Birtinya	Queensland
Australia	Monash Health	Clayton	Victoria
Australia	Concord Repatriation General Hospital	Concord	New South Wales
Australia	Northern Beaches Hospital	Frenchs Forest	New South Wales
Australia	Canberra Hospital	Garran	Australian Capital Territory
Australia	Royal Brisbane Women's Hospital	Herston	Queensland
Australia	Western Health - Sunshine Hospital	Saint Albans	Victoria
Australia	Royal North Shore Hospital	Wahroonga	New South Wales
Australia	Sydney Adventist Hospital	Wahroonga	New South Wales
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Brazil	Irmandade da Santa Casa de Misericordia de Porto Alegre -ISCMPA	Bairro Santa Teresa	Porto Alegre
Brazil	Felicio Rocho Foundation - Hospital Felicio Rocho	Belo Horizonte	Minas Gerais
Brazil	Fundacao Hospitalar Sao Francisco de Assis	Belo Horizonte	Minas Gerais
Brazil	PROCARDIO Clinica Cardiologica	Blumenau	SC
Brazil	Fundacao Pro-Rim	Boa Vista	Joinville
Brazil	Hospital Arquidiocesano Consul Carlos Reneaux	Brusque	Santa Catarina
Brazil	Sociedade Hospitalar Angelina Caron	Campina Grande Do Sul	Parana
Brazil	Sociedade Campineira de Educacao e Instrucao (SCEI)	Campinas	Sao Paulo
Brazil	Instituto Pro Renal Brazil	Curitiba	Parana
Brazil	Clinica Senhor do Bonfim	Feira De Santana	Bahia
Brazil	Eurolatino Natal Pesquisas Medicas Ltda	Petropolis	Natal
Brazil	Hospital de Clinicas de Porto Alegre	Porto Alegre	Rio Grande Do Sul
Brazil	Medical School of Botucatu of the Paulista State University - UNESP	Rubiao Junior	Botucatu
Brazil	Clinica Senhor do Bonfim	Salvador	Bahia
Brazil	Santa Casa de Misericordia de Belo Horizonte	Santa Efigênia	Belo Horizonte
Brazil	Praxis Pesquisa Medica S/S	Santo André	Sao Paulo
Brazil	Servico Ubaense de Nefrologia Ltda	Uba	Minas Gerais
Brazil	Santa Casa de Misericordia de Votuporanga	Votuporanga	Sao Paulo
Canada	Foothills Hospital	Calgary	Alberta
Canada	University of Alberta	Edmonton	Alberta
Canada	Queen Elizabeth II Health Science Centre	Halifax	Nova Scotia
Canada	St. Joseph's Healthcare	Hamilton	Ontario
Canada	Dr.J. Conley	Kamloops	British Colombia
Canada	Dr. Marie Michaud	Kelowna	British Colombia
Canada	Queen's University at Kingston, Division of Nephrology	Kingston	Ontario
Canada	Victoria Hospital	London	Ontario
Canada	Dr. Annie-Claire Nadeau-Fredette	Montreal	Quebec
Canada	Hopital du Sacre-Coeur de Montreal	Montreal	Quebec
Canada	Centre Hospitalier de l'Universite de Montreal (CHUM)	Montréal	Quebec
Canada	Ottawa Hospital Research Institute	Ottawa	Ontario
Canada	CHU de Quebec L'Hotel-Dieu de Quebec	Québec
Canada	Health Sciences North Research Institute	Sudbury	Ontario
Canada	Dr. Joanna Sasal	Toronto	Ontario
Canada	St. Michael's Hospital	Toronto	Ontario
Canada	St. Paul's Hospital	Vancouver	British Colombia
Ecuador	Clinefnorte CIA Ltda	Quito	Pichincha
Ecuador	Nefrology	Quito	Pichincha
Ecuador	Nefromedi SA	Quito	Pichincha
India	CBCI Society for Medical Education	Bangalore	Karnataka
India	Narayana Hrudayalaya Limited	Bangalore	Karnataka
India	Fortis Hospitals	Bengaluru	Karnataka
India	Apollo Hospitals	Chennai	Tamil Nadu
India	Vijaya Hospital	Chennai	Tamil Nadu
India	AsterMedCity	Cochin	Kerala
India	AIMS Hospital Mumbai	Dombivli	Maharashtra
India	Nizam's Institute of Medical Sciences	Hyderabad	Telangana
India	Osmania General Hospital	Hyderabad	Telegana
India	Caritas Hospital	Kottayam	Kerala
India	K S Hegde Medical Academy	Mangaluru	Karnataka
India	Ashirwad Hospital Mumbai	Mumbai	Maharashtra
India	National Health and Education Society	Mumbai	Maharashtra
India	Dhadiwal Hospital	Nashik	Maharashtra
India	Madras Medical College Chennai	Park Town	Chennai
India	Mahatma Gandhi Medical College and Reserach Institute	Puducherry	Tamil Nadu
India	ACE Hospital Une	Pune	Maharashtra
India	Aditya Birla Hospital	Pune	Maharashtra
India	Nanjappa Hospitals Shimoga	Shimoga	Karnataka
India	Yashoda Hospital	Susundra	Telangana
Malaysia	Universiti Teknologi Mara (UiTM)	Batu Caves	Selangor
Malaysia	Universiti Kebangsaan Malaysia	Cheras	Kuala Lumpur
Malaysia	Hospital Pulau Pinang	George Town	Pulau Pinang
Malaysia	Hospital Raja Permaisuri Bainun, IPOH	Ipoh	Perak
Malaysia	Hospital Sultanah Aminah, Johor Bahru	Johor Bahru	Johor
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 Pakar Sultanah Fatimah	Muar	Johor
Malaysia	Hospital Tuanku Jaafar, Seremban	Seremban
Malaysia	Hospital Ampang	Setapak
Malaysia	Hospital Taiping	Taiping	Perak
New Zealand	Auckland City Hospital	Auckland
New Zealand	Dunedin Hospital	Dunedin
New Zealand	Waikato Hospital	Hamilton	Waikato
New Zealand	Hawkes Bay Hospital	Hastings
New Zealand	Taranaki Base Hospital	New Plymouth
New Zealand	Palmerston North Hospital	Palmerston North
New Zealand	North Shore Hospital	Takapuna	Auckland
New Zealand	Whangarei Hospital	Whangarei
Philippines	Philippines General Hospital	Ermita	Manila
Philippines	Medical City General Hospital	Pasig City	Manila
Philippines	National Kidney and Transplant Institute	Quezon City	Manila
United Kingdom	Aberdeen Royal Infirmary	Aberdeen
United Kingdom	Belfast City Hospital	Belfast
United Kingdom	Southmead Hospital	Bristol
United Kingdom	Kent & Canterbury Hospital	Canterbury	Kent
United Kingdom	University Hospital of Whales Health Park	Cardiff
United Kingdom	Royal Derby Hospital	Derby
United Kingdom	Ninewells Hospital	Dundee
United Kingdom	Ulster Hospital	Dundonald	Belfast
United Kingdom	Queen Elizabeth University Hospital	Glasgow
United Kingdom	Churchill Hospital	Headington	Oxford
United Kingdom	Kings College Hospital	London
United Kingdom	The Royal London Hospital	London
United Kingdom	Daisy Hill Hospital	Newry	Down
United Kingdom	City Hospital	Nottingham
United Kingdom	Salford Royal Hospital	Salford
Uruguay	Canimel Center	Melo	Cerro Largo
Uruguay	Cedina Center	Montevideo
Uruguay	Centro de Asistencia del Sindicato Medico del Uruguay-Institucion de Asistencia medica Privada (CASMU-IAMPP)	Montevideo
Uruguay	Hospital de Clinicas "Dr. Manuel Quintela"	Montevideo
Uruguay	SEDIC Center	Montevideo

Sponsors (2)

Lead Sponsor	Collaborator
Population Health Research Institute	Canadian Institutes of Health Research (CIHR)

Countries where clinical trial is conducted

Australia,  Brazil,  Canada,  Ecuador,  India,  Malaysia,  New Zealand,  Philippines,  United Kingdom,  Uruguay, 

References & Publications (2)

Quach K, Lvtvyn L, Baigent C, Bueti J, Garg AX, Hawley C, Haynes R, Manns B, Perkovic V, Rabbat CG, Wald R, Walsh M. The Safety and Efficacy of Mineralocorticoid Receptor Antagonists in Patients Who Require Dialysis: A Systematic Review and Meta-analysis. Am J Kidney Dis. 2016 Oct;68(4):591-598. doi: 10.1053/j.ajkd.2016.04.011. Epub 2016 Jun 3. — View Citation

Walsh M, Manns B, Garg AX, Bueti J, Rabbat C, Smyth A, Tyrwhitt J, Bosch J, Gao P, Devereaux PJ, Wald R. The Safety of Eplerenone in Hemodialysis Patients: A Noninferiority Randomized Controlled Trial. Clin J Am Soc Nephrol. 2015 Sep 4;10(9):1602-8. doi: 10.2215/CJN.12371214. Epub 2015 Jul 2. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	CV Death or Hospitalization for Heart Failure		up to 5 years
Secondary	Cause specific death		up to 5 years
Secondary	Hospitalization for Heart Failure		up to 5 years
Secondary	All-cause death		up to 5 years
Secondary	All-cause Hospitalization		up to 5 years
Secondary	Hospitalization for hyperkalemia		up to 5 years