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

Sponsor
Population Health Research Institute (Other)
Overall Status
Recruiting
CT.gov ID
NCT03020303
Collaborator
Canadian Institutes of Health Research (CIHR) (Other)
2,750
Enrollment
86
Locations
2
Arms
73.8
Anticipated Duration (Months)
32
Patients Per Site
0.4
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Spironolactone 25Mg Tablet
  • Drug: Placebo Oral Tablet
 Phase 3

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 Design

Study Type:
Interventional
Anticipated Enrollment :
2750 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Prevention
Official Title:
Aldosterone bloCkade for Health Improvement EValuation in End-stage Renal Disease
Actual Study Start Date :
Jul 7, 2017
Anticipated Primary Completion Date :
Apr 1, 2023
Anticipated Study Completion Date :
Sep 1, 2023

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: Placebo Oral Tablet

A tablet with no active medication that will be an exact match of the active spironolactone in taste and appearance

Drug: 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.
Active Comparator: Spironolactone 25 MG Tablet

25 mg of active spironolactone in tablet form

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.

Outcome Measures

Primary Outcome Measures

  1. CV Death or Hospitalization for Heart Failure [up to 5 years]

Secondary Outcome Measures

  1. Cause specific death [up to 5 years]

  2. Hospitalization for Heart Failure [up to 5 years]

  3. All-cause death [up to 5 years]

  4. All-cause Hospitalization [up to 5 years]

  5. Hospitalization for hyperkalemia [up to 5 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  1. Age

  2. ≥45 years or

  3. ≥18 with a history of diabetes

  4. On dialysis ≥ 90 days

  5. On either

  6. Hemodialysis prescribed at least 2 treatments per week or

  7. Peritoneal dialysis prescribed with at least 1 exchange daily

  8. Provides informed consent

Exclusion Criteria:

  1. Hyperkalemia

  2. Serum potassium >5.8 mmol/L in the 6 weeks prior to enrollment or

  3. Serum potassium >6.0 mmol/L during active run-in

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

  5. Known sensitivity or allergy to spironolactone

  6. Current or planned pregnancy or breastfeeding

  7. Scheduled living related donor renal transplant

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

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

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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Canberra Hospital Garran Australian Capital Territory Australia 2605
2 Concord Repatriation General Hospital Concord New South Wales Australia 2139
3 Royal North Shore Hospital Wahroonga New South Wales Australia 2076
4 Sydney Adventist Hospital Wahroonga New South Wales Australia 2076
5 Sunshine Coast University Hospital Birtinya Queensland Australia 4575
6 Royal Brisbane Women's Hospital Herston Queensland Australia 4029
7 Princess Alexandra Hospital Woolloongabba Queensland Australia 4102
8 Monash Health Clayton Australia 3168
9 Santa Casa de Misericordia de Belo Horizonte Santa Efigênia Belo Horizonte Brazil 30150221
10 Medical School of Botucatu of the Paulista State University - UNESP Rubiao Junior Botucatu Brazil 18618-687
11 Fundacao Pro-Rim Boa Vista Joinville Brazil 89227680
12 Felicio Rocho Foundation - Hospital Felicio Rocho Belo Horizonte Minas Gerais Brazil 30110934
13 Fundacao Hospitalar Sao Francisco de Assis Belo Horizonte Minas Gerais Brazil 31110580
14 Servico Ubaense de Nefrologia Ltda Uba Minas Gerais Brazil 36500008
15 Eurolatino Natal Pesquisas Medicas Ltda Petropolis Natal Brazil 59020500
16 Sociedade Hospitalar Angelina Caron Campina Grande Do Sul Parana Brazil 83430000
17 Irmandade da Santa Casa de Misericordia de Porto Alegre -ISCMPA Bairro Santa Teresa Porto Alegre Brazil 90020090
18 Praxis Pesquisa Medica S/S Santo André Sao Paulo Brazil 09090 790
19 PROCARDIO Clinica Cardiologica Blumenau SC Brazil 89010500
20 Foothills Hospital Calgary Alberta Canada T2N 2T9
21 University of Alberta Edmonton Alberta Canada T6G 2G3
22 Dr.J. Conley Kamloops British Colombia Canada V2C 2T1
23 Dr. Marie Michaud Kelowna British Colombia Canada V1Y 1T2
24 St. Paul's Hospital Vancouver British Colombia Canada V6Z 1Y6
25 Queen Elizabeth II Health Science Centre Halifax Nova Scotia Canada B3H 1V7
26 St. Joseph's Healthcare Hamilton Ontario Canada L8N 4A6
27 Queen's University at Kingston, Division of Nephrology Kingston Ontario Canada
28 Victoria Hospital London Ontario Canada N6A 5W9
29 Ottawa Hospital Research Institute Ottawa Ontario Canada K1Y 4E9
30 Health Sciences North Research Institute Sudbury Ontario Canada P3E 5J1
31 St. Michael's Hospital Toronto Ontario Canada M5B 1W8
32 Dr. Joanna Sasal Toronto Ontario Canada M6R 1B5
33 Dr. Annie-Claire Nadeau-Fredette Montreal Quebec Canada H1T 2M4
34 Hopital du Sacre-Coeur de Montreal Montreal Quebec Canada H4J 1C5
35 Centre Hospitalier de l'Universite de Montreal (CHUM) Montréal Quebec Canada H2W 1T8
36 CHU de Quebec L'Hotel-Dieu de Quebec Québec Canada G1R 2J6
37 Nefrology Quito Pichincha Ecuador 170131
38 Clinefnorte CIA Ltda Quito Pichincha Ecuador 170303
39 Nefromedi SA Quito Pichincha Ecuador 170601
40 Madras Medical College Chennai Park Town Chennai India 600003
41 CBCI Society for Medical Education Bangalore Karnataka India 560034
42 Narayana Hrudayalaya Limited Bangalore Karnataka India 560099
43 Fortis Hospitals Bengaluru Karnataka India 560076
44 K S Hegde Medical Academy Mangaluru Karnataka India 575018
45 Nanjappa Hospitals Shimoga Shimoga Karnataka India 577201
46 Caritas Hospital Kottayam Kerala India 686630
47 AIMS Hospital Mumbai Dombivli Maharashtra India 421203
48 National Health and Education Society Mumbai Maharashtra India 400016
49 Ashirwad Hospital Mumbai Mumbai Maharashtra India 421004
50 ACE Hospital Une Pune Maharashtra India 411004
51 Aditya Birla Hospital Pune Maharashtra India 411033
52 Apollo Hospitals Chennai Tamil Nadu India 600081
53 Mahatma Gandhi Medical College and Reserach Institute Puducherry Tamil Nadu India 607402
54 Nizam's Institute of Medical Sciences Hyderabad Telangana India 500082
55 Yashoda Hospital Susundra Telangana India 500003
56 Osmania General Hospital Hyderabad Telegana India 500012
57 Hospital Sultanah Aminah, Johor Bahru Johor Bahru Johor Malaysia 80100
58 Hospital Pakar Sultanah Fatimah Muar Johor Malaysia
59 Universiti Kebangsaan Malaysia Cheras Kuala Lumpur Malaysia 56000
60 Hospital Raja Permaisuri Bainun, IPOH Ipoh Perak Malaysia 30990
61 Hospital Taiping Taiping Perak Malaysia 34000
62 Hospital Pulau Pinang George Town Pulau Pinang Malaysia 10990
63 Universiti Teknologi Mara (UiTM) Batu Caves Selangor Malaysia
64 Hospital Kajang Kajang Selangor Malaysia 43000
65 Hospital Kuala Lumpur Kuala Lumpur Malaysia 42896
66 University Malaya Medical Centre (UMMC) Kuala Lumpur Malaysia 59100
67 Hospital Sultanah Nur Zahirah Kuala Terengganu Kuala Terengganu Malaysia 33158
68 Hospital Tengku Ampuan Afzan, Kuantan Kuantan Malaysia 29142
69 Hospital Tuanku Jaafar, Seremban Seremban Malaysia 25167
70 Hospital Ampang Setapak Malaysia 53200
71 North Shore Hospital Takapuna Auckland New Zealand 0620
72 Auckland City Hospital Auckland New Zealand
73 Dunedin Hospital Dunedin New Zealand 9016
74 Hawkes Bay Hospital Hastings New Zealand 4120
75 Taranaki Base Hospital New Plymouth New Zealand 4310
76 Palmerston North Hospital Palmerston North New Zealand 4442
77 Whangarei Hospital Whangarei New Zealand 0148
78 Philippines General Hospital Ermita Manila Philippines 1000
79 Medical City General Hospital Pasig City Manila Philippines 1605
80 National Kidney and Transplant Institute Quezon City Manila Philippines 1101
81 Institute of Cardiovascular and Medical Sciences Glasgow UK United Kingdom G128TA
82 Canimel Center Melo Cerro Largo Uruguay
83 Hospital de Clinicas "Dr. Manuel Quintela" Montevideo Uruguay 11600
84 SEDIC Center Montevideo Uruguay 11800
85 Cedina Center Montevideo Uruguay
86 Centro de Asistencia del Sindicato Medico del Uruguay-Institucion de Asistencia medica Privada (CASMU-IAMPP) Montevideo Uruguay

Sponsors and Collaborators

  • Population Health Research Institute
  • Canadian Institutes of Health Research (CIHR)

Investigators

  • Principal Investigator: Michael Walsh, MD, PhD, McMaster University
  • Study Chair: PJ Devereaux, MD, PhD, McMaster University

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
Population Health Research Institute
ClinicalTrials.gov Identifier:
NCT03020303
Other Study ID Numbers:
  • ACHIEVE
First Posted:
Jan 13, 2017
Last Update Posted:
Oct 29, 2020
Last Verified:
Oct 1, 2020
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Product Manufactured in and Exported from the U.S.:
No
Additional relevant MeSH terms:
Kidney Diseases
Kidney Failure, Chronic
Spironolactone

Study Results

No Results Posted as of Oct 29, 2020