Clinical trial NCT03020303: Aldosterone bloCkade for Health Improvement EValuation in End-stage Renal Disease
Official title: Aldosterone bloCkade for Health Improvement EValuation in End-stage Renal Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Endstage Renal Disease
Lead sponsor: Population Health Research Institute
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
First posted: 2017-01-13
Enrollment: 2538
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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).

Eligibility criteria: 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

Primary outcomes:
measure: CV Death or Hospitalization for Heart Failure
timeFrame: up to 5 years
Secondary outcomes:
measure: Cause specific death
timeFrame: up to 5 years
measure: Hospitalization for Heart Failure
timeFrame: up to 5 years
measure: All-cause death
timeFrame: up to 5 years
measure: All-cause Hospitalization
timeFrame: up to 5 years
measure: Hospitalization for hyperkalemia
timeFrame: up to 5 years
Other outcomes:
Locations:
city: Garran
country: Australia
facility: Canberra Hospital
state: Australian Capital Territory
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
state: New South Wales
city: Frenchs Forest
country: Australia
facility: Northern Beaches Hospital
state: New South Wales
city: Wahroonga
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Wahroonga
country: Australia
facility: Sydney Adventist Hospital
state: New South Wales
city: Birtinya
country: Australia
facility: Sunshine Coast University Hospital
state: Queensland
city: Herston
country: Australia
facility: Royal Brisbane Women&#39;s Hospital
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Clayton
country: Australia
facility: Monash Health
state: Victoria
city: Saint Albans
country: Australia
facility: Western Health - Sunshine Hospital
state: Victoria
city: Santa Efigênia
country: Brazil
facility: Santa Casa de Misericordia de Belo Horizonte
state: Belo Horizonte
city: Rubiao Junior
country: Brazil
facility: Medical School of Botucatu of the Paulista State University - UNESP
state: Botucatu
city: Boa Vista
country: Brazil
facility: Fundacao Pro-Rim
state: Joinville
city: Belo Horizonte
country: Brazil
facility: Felicio Rocho Foundation - Hospital Felicio Rocho
state: Minas Gerais
city: Belo Horizonte
country: Brazil
facility: Fundacao Hospitalar Sao Francisco de Assis
state: Minas Gerais
city: Uba
country: Brazil
facility: Servico Ubaense de Nefrologia Ltda
state: Minas Gerais
city: Campina Grande Do Sul
country: Brazil
facility: Sociedade Hospitalar Angelina Caron
state: Parana
city: Curitiba
country: Brazil
facility: Instituto Pro Renal Brazil
state: Parana
city: Bairro Santa Teresa
country: Brazil
facility: Irmandade da Santa Casa de Misericordia de Porto Alegre -ISCMPA
state: Porto Alegre
city: Porto Alegre
country: Brazil
facility: Hospital de Clinicas de Porto Alegre
state: Rio Grande do Sul
city: Brusque
country: Brazil
facility: Hospital Arquidiocesano Consul Carlos Reneaux
state: Santa Catarina
city: Santo André
country: Brazil
facility: Praxis Pesquisa Medica S/S
state: Sao Paulo
city: Votuporanga
country: Brazil
facility: Santa Casa de Misericordia de Votuporanga
state: Sao Paulo
city: Blumenau
country: Brazil
facility: PROCARDIO Clinica Cardiologica
state: South Carolina
city: Bela Vista
country: Brazil
facility: Hospital Alemao Oswaldo Cruz
city: Ponta Grossa
country: Brazil
facility: Santa Casa de Misericordia de Ponta Grossa
city: Calgary
country: Canada
facility: Foothills Hospital
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Kamloops
country: Canada
facility: Royal Inland Hospital
state: British Colombia
city: Kelowna
country: Canada
facility: Kelowna General Hospital
state: British Colombia
city: Vancouver
country: Canada
facility: St. Pauls Hospital
state: British Colombia
city: Penticton
country: Canada
facility: Penticton Regional Hospital
state: British Columbia
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Science Centre
state: Nova Scotia
city: Sydney
country: Canada
facility: Cape Breton Regional Hospital
state: Nova Scotia
city: Hamilton
country: Canada
facility: St. Joseph's Healthcare
state: Ontario
city: Kingston
country: Canada
facility: Queens University at Kingston General Hospital, Division of Nephrology
state: Ontario
city: London
country: Canada
facility: Victoria Hospital
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital Research Institute
state: Ontario
city: Sudbury
country: Canada
facility: Health Sciences North Research Institute
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: St. Josephs, Toronto
state: Ontario
city: Toronto
country: Canada
facility: Humber River Health
state: Ontario
city: Montreal
country: Canada
facility: CIUSSS Hopital Maisonneuve- Rosemont
state: Quebec
city: Montreal
country: Canada
facility: Hopital du Sacre-Coeur de Montreal
state: Quebec
city: Montreal
country: Canada
facility: The Sir Mortimer B. Davis Jewish General Hospital
state: Quebec
city: Montréal
country: Canada
facility: Centre Hospitalier de l&#39;Universite de Montreal (CHUM)
state: Quebec
city: Québec
country: Canada
facility: CHU de Quebec L'Hotel-Dieu de Quebec
state: Quebec
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University Peoples Hospital
state: Beijing
city: Yinchuan
country: China
facility: General Hospital of Ningxia Medical University
state: Ningxia
city: Baotou
country: China
facility: The First Affiliated Hospital of Baotou Medical College
city: Beijing
country: China
facility: Beijing Miyun District Hospital
city: Beijing
country: China
facility: Beijing Tongren Hospital, Capital Medical University
city: Beijing
country: China
facility: Emergency General Hospital
city: Changchun
country: China
facility: Faw General Hospital of Jilin Province
city: Enshi
country: China
facility: The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture
city: Huai'an
country: China
facility: Huai'an First Peoples Hospital
city: Kunming
country: China
facility: The First Hospital of Kunming
city: Lanzhou
country: China
facility: Gansu Baoshihua Hospital
city: Luoyang
country: China
facility: Yichuan County Traditional Chinese Medicine Hospital
city: Shanghai
country: China
facility: Shanghai Tongji Hospital
city: Shanxi
country: China
facility: Shanxi Provincial Peoples Hospital
city: Suqian
country: China
facility: Shuyang County Hospital of Traditional Chinese Medicine
city: Suqian
country: China
facility: Sihong County Fenjinting Hospital
city: Tianjin
country: China
facility: Tianjin Fifth Central Hospital
city: Tianjin
country: China
facility: Tianjin Third Central Hospital
city: Tongliao
country: China
facility: Tongiao City Hospital
city: Xinxiang
country: China
facility: Xinxiang First Peoples Hospital
city: Xuzhou
country: China
facility: General Hospital of Xuzhou Mining Group
city: Yuxi
country: China
facility: Peoples Hospital of Yuxi City
city: Zhongwei
country: China
facility: Peoples Hospital of Zhongwei
city: Quito
country: Ecuador
facility: Clinefnorte CIA Ltda
state: Pichincha
city: Quito
country: Ecuador
facility: Nefromedic SA
state: Pichincha
city: Park Town
country: India
facility: Madras Medical College Chennai
state: Chennai
city: Bangalore
country: India
facility: Narayana Hrudayalaya Limited
state: Karnataka
city: Bengaluru
country: India
facility: Fortis Hospitals
state: Karnataka
city: Mangaluru
country: India
facility: K S Hegde Medical Academy
state: Karnataka
city: Shimoga
country: India
facility: Nanjappa Hospitals Shimoga
state: Karnataka
city: Cochin
country: India
facility: AsterMedCity
state: Kerala
city: Kottayam
country: India
facility: Caritas Hospital
state: Kerala
city: Dombivli
country: India
facility: AIMS Hospital Mumbai
state: Maharashtra
city: Mumbai
country: India
facility: National Health and Education Society
state: Maharashtra
city: Mumbai
country: India
facility: Ashirwad Hospital Mumbai
state: Maharashtra
city: Nashik
country: India
facility: Dhadiwal Hospital
state: Maharashtra
city: Pune
country: India
facility: ACE Hospital Une
state: Maharashtra
city: Pune
country: India
facility: Aditya Birla Hospital
state: Maharashtra
city: Chennai
country: India
facility: Vijaya Hospital
state: Tamil Nadu
city: Chennai
country: India
facility: Apollo Hospitals
state: Tamil Nadu
city: Hyderabad
country: India
facility: Nizams Institute of Medical Sciences
state: Telangana
city: Hyderabad
country: India
facility: Osmania General Hospital
state: Telegana
city: Madurai
country: India
facility: Government Rajaji Hospital, Madurai
city: Mangalore
country: India
facility: Father Muller Medical College
city: Nagpur
country: India
facility: Seven Star Hospital
city: Johor Bahru
country: Malaysia
facility: Hospital Sultanah Aminah, Johor Bahru
state: Johor
city: Muar
country: Malaysia
facility: Hospital Pakar Sultanah Fatimah
state: Johor
city: Taiping
country: Malaysia
facility: Hospital Taiping
state: Perak
city: George Town
country: Malaysia
facility: Hospital Pulau Pinang
state: Pulau Pinang
city: Kajang
country: Malaysia
facility: Hospital Kajang
state: Selangor
city: Klang
country: Malaysia
facility: Hospital Tengku Ampuan Rahimah Klang
state: Selangor
city: Kuala Lumpur
country: Malaysia
facility: Hospital Kuala Lumpur
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Centre (UMMC)
city: Kuala Terengganu
country: Malaysia
facility: Hospital Sultanah Nur Zahirah Kuala Terengganu
city: Kuantan
country: Malaysia
facility: Hospital Tengku Ampuan Afzan, Kuantan
city: Seremban
country: Malaysia
facility: Hospital Tuanku Jaafar, Seremban
city: Setapak
country: Malaysia
facility: Hospital Ampang
city: Takapuna
country: New Zealand
facility: North Shore Hospital
state: Auckland
city: Hamilton
country: New Zealand
facility: Waikato Hospital
state: Waikato
city: Dunedin
country: New Zealand
facility: Dunedin Hospital
city: Hastings
country: New Zealand
facility: Hawkes Bay Hospital
city: Palmerston North
country: New Zealand
facility: Palmerston North Hospital
city: Whangarei
country: New Zealand
facility: Whangarei Hospital
city: Ermita
country: Philippines
facility: Philippines General Hospital
state: Manila
city: Quezon City
country: Philippines
facility: National Kidney and Transplant Institute
state: Manila
city: Ankara
country: Turkey
facility: Hacettepe University Hospitals Hemodialysis Center
city: Eskişehir
country: Turkey
facility: Osmangazi University
city: Istanbul
country: Turkey
facility: Memorial Service Hospital
city: Dundonald
country: United Kingdom
facility: Ulster Hospital
state: Belfast
city: Newry
country: United Kingdom
facility: Daisy Hill Hospital
state: Down
city: Canterbury
country: United Kingdom
facility: East Kent Canterbury Hospital
state: Kent
city: Headington
country: United Kingdom
facility: Churchill Hospital
state: Oxford
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary
city: Belfast
country: United Kingdom
facility: Belfast City Hospital
city: Birmingham
country: United Kingdom
facility: Birmingham Hospitals
city: Bristol
country: United Kingdom
facility: Southmead Hospital
city: Cardiff
country: United Kingdom
facility: University Hospital of Whales Health Park
city: Carshalton
country: United Kingdom
facility: Epsom St. Helier
city: Derby
country: United Kingdom
facility: Royal Derby Hospital
city: Dundee
country: United Kingdom
facility: Ninewells Hospital
city: Glasgow
country: United Kingdom
facility: Queen Elizabeth University Hospital
city: Leicester
country: United Kingdom
facility: Leicester General Hospital
city: Liverpool
country: United Kingdom
facility: Liverpool University Hospitals
city: London
country: United Kingdom
facility: The Royal London Hospital
city: London
country: United Kingdom
facility: Kings College Hospital
city: Middlesbrough
country: United Kingdom
facility: South Tees James Cook Hospital
city: Nottingham
country: United Kingdom
facility: City Hospital
city: Salford
country: United Kingdom
facility: Salford Royal Hospital
city: Stoke-on-Trent
country: United Kingdom
facility: Royal Stoke University Hospital
city: Melo
country: Uruguay
facility: Canimel Center
state: Cerro Largo
city: Montevideo
country: Uruguay
facility: SEDIC Center
city: Montevideo
country: Uruguay
facility: Cedina Center
city: Montevideo
country: Uruguay
facility: Centro de Asistencia del Sindicato Medico del Uruguay-Institucion de Asistencia medica Privada (CASMU-IAMPP)
Study officials:
affiliation: McMaster University
name: Michael Walsh, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: McMaster University
name: PJ Devereaux, MD, PhD
role: STUDY_CHAIR
References:
citation: 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.
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.
citation: Soomro QH, Charytan DM. Mineralocorticoid Receptor Antagonists and Cardiovascular Health with Kidney Failure. Clin J Am Soc Nephrol. 2021 Jun;16(6):843-845. doi: 10.2215/CJN.04460421. No abstract available.
citation: 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, Felix C, Mark PB, Li Z, Tyrwhitt J, Wilkinson J, Sheridan P, Yuan F, Walsh M; ACHIEVE investigators. Three week compared to seven week run-in period length and the assessment of pre-randomization adherence: A study within a trial. Contemp Clin Trials. 2021 Aug;107:106466. doi: 10.1016/j.cct.2021.106466. Epub 2021 Jun 5.
citation: Hasegawa T, Nishiwaki H, Ota E, Levack WM, Noma H. Aldosterone antagonists for people with chronic kidney disease requiring dialysis. Cochrane Database Syst Rev. 2021 Feb 15;2(2):CD013109. doi: 10.1002/14651858.CD013109.pub2.