NCT01848639

Brief Summary

This study is designed to etablish the effects of spironolactone in comparison to placebo on the composite endpoint of nonfatal Myocardial Infarction (MI) and acute coronary syndrome, hospitalization for heart failure, nonfatal stroke or cardiovascular-induced death. The primary endpoint will be the time to onset of the first incident.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
823

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started Jun 2013

Longer than P75 for phase_3

Geographic Reach
3 countries

70 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 3, 2013

Completed
4 days until next milestone

First Posted

Study publicly available on registry

May 7, 2013

Completed
25 days until next milestone

Study Start

First participant enrolled

June 1, 2013

Completed
9.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2022

Completed
Last Updated

October 10, 2023

Status Verified

October 1, 2023

Enrollment Period

9.4 years

First QC Date

May 3, 2013

Last Update Submit

October 5, 2023

Conditions

Keywords

chronic kidney diseaseend-stage renal diseasehemodialysis (ESRD)cardiovascular morbimortalityaldosterone antagonistspironolactone

Outcome Measures

Primary Outcomes (1)

  • The time to onset of the first incident :non-fatal MI or acute coronary syndrome or hospitalization for heart failure or nonfatal stroke or cardiovascular (CV) death

    25 months

Secondary Outcomes (14)

  • Determine the effects of spironolactone compared to placebo on the composite winratio endpoint

    24 months

  • Determine the effects of spironolactone compared to placebo on the composite winratio endpoint

    24 months

  • non-cardiovascular mortality rate

    24 months

  • cumulative accident rates forming the primary endpoint

    24 months

  • The time of survival without a major CV event (non fatal MI, acute coronary syndrome, hospitalization for heart failure, non-fatal stroke, cardiac arrest resuscitation)

    24 months

  • +9 more secondary outcomes

Other Outcomes (2)

  • Ancillary study:establishment of a biological collection (serum bank and DNA biobank) for future biomarker studies

    24 months

  • Ancillary study:morbimortality data

    3, 5 and 10 years of follow-up after the double-blind study

Study Arms (2)

Spironolactone

ACTIVE COMPARATOR

After a month in run-in period under 25 mg per 2 days of spironolactone administered per os in practice after dialysis session three times a week, patients will be randomized to spironolactone. The dose should be increased to 25 mg once daily and could be adjusted in using an algorithm used in the EPHESUS and EMPHASIS-HF trials.

Drug: Spironolactone

Placebo

PLACEBO COMPARATOR

After a month in run-in period under 25 mg per 2 days of spironolactone administered per os in practice after dialysis session three times a week, patients will be randomized to placebo. The dose should be increased to 25 mg once daily and could be adjusted in using an algorithm used in the EPHESUS and EMPHASIS-HF trials.

Drug: Placebo

Interventions

After a month in run-in period under 25 mg per 2 days of spironolactone administered per os in practice after dialysis session three times a week, patients will be randomized to spironolactone. The dose should be increased to 25 mg once daily and could be adjusted in using an algorithm used in the EPHESUS and EMPHASIS-HF trials.

Spironolactone

After a month in run-in period under 25 mg per 2 days of spironolactone administered per os in practice after dialysis session three times a week, patients will be randomized to placebo. The dose should be increased to 25 mg once daily and could be adjusted in using an algorithm used in the EPHESUS and EMPHASIS-HF trials.

Placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Written informed consent.
  • Adult men and women on HD for at least 45 days for ESRD regardless of the etiology including diabetes, with at least 3 HD sessions per week
  • Presenting at least one of the follow comorbidities, cardiovascular abnormalities or CV risk factors:
  • Left ventricular hypertrophy defined by left ventricular mass \> 130 g/m2 in men and 100 g/m2 in women (echocardiography)
  • OR Cornell (RaVL + SV3) \>28 mm in men, \> 20 mm in women(ECG)
  • OR left ventricular ejection fraction \< 40%
  • OR large QRS \> 0.14 sec
  • OR history of cardiovascular disease: coronary artery disease, symptomatic lower limb peripheral arterial disease, carotid or renal artery stenosis \> 50%, stroke, hospitalization for heart failure, permanent atrial fibrillation (AF), oral anticoagulant treatment for AF, valvular heart prosthesis,
  • OR CRP \> 5 mg/l for 3 months without infectious or neoplastic disease documented in progress

You may not qualify if:

  • history of hypersensitivity to spironolactone or galactose intolerance
  • the Lapp lactase deficiency or malabsorption of glucose or galactose
  • hyperkalemia \> 5.5 mmol/l during the two weeks prior to enrolment
  • history of unscheduled hemodialysis for hyperkalemia during the last six months
  • hospitalization for hyperkalemia during the last six months
  • patients with imperative indication of a combination of ACEI and sartan or renin inhibitor (each being authorized separately), NSAIDS, Cox-2 inhibitors
  • kidney transplant scheduled within the year
  • symptomatic interdialytic hypotension
  • acute systemic disease
  • uncompensated hypothyroidism
  • acute hyperthyroidism
  • cardiac transplant
  • severe uncontrolled arrhythmia
  • stroke within 3 months prior to enrolment
  • recent (1 month) or planned coronary revascularization by angioplasty
  • +7 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (70)

Hôpital Erasme- Bruxelles

Brussels, 1070, Belgium

Location

CH Ardeche Nord

Annonay, Ardeche, 07100, France

Location

CHU Amiens

Amiens, 80054, France

Location

CH Avignon

Avignon, 84000, France

Location

CHU Besançon

Besançon, 25000, France

Location

CH Boulogne Sur Mer

Boulogne-sur-Mer, 62321, France

Location

CHRU Brest

Brest, 29609, France

Location

CHU Caen

Caen, 14033, France

Location

CH Cahors

Cahors, 46000, France

Location

CH Chambéry

Chambéry, 73000, France

Location

CHPC Cherbourg

Cherbourg, 50100, France

Location

AURAL Colmar

Colmar, 68000, France

Location

Hopitaux Civils de Colmar

Colmar, 68024, France

Location

APHP Henri Mondor

Créteil, 94010, France

Location

CHU Dijon Hôpital du Bocage

Dijon, 21079, France

Location

AGDUC Grenoble

Grenoble, 38043, France

Location

AURAL Haguenau

Haguenau, 67500, France

Location

CH Haguenau

Haguenau, 67500, France

Location

La Roche Sur Yon

La Roche-sur-Yon, 85000, France

Location

Polyclinique de Lagny

Lagny, 77400, France

Location

Clinique Lille

Lille, 59000, France

Location

CHU Lille

Lille, 59037, France

Location

ALURAD Limoges

Limoges, 87000, France

Location

CHU Limoges

Limoges, 87042, France

Location

CHU de Lyon

Lyon, 69003, France

Location

AURAL La Croix Rousse

Lyon, 69004, France

Location

CH St Joseph-St Luc

Lyon, 69007, France

Location

AURAL Lyon

Lyon, 69008, France

Location

Clinique Bouchard

Marseille, 13006, France

Location

Adpc Marseille

Marseille, 13009, France

Location

APHM Marseille

Marseille, 13385, France

Location

Association de Metz

Metz, 57000, France

Location

ALTIR Metz

Metz, 58085, France

Location

CHR Metz-Thionville

Metz, 58085, France

Location

AURAL Mulhouse

Mulhouse, 68100, France

Location

CH Mulhouse

Mulhouse, 68100, France

Location

CHU Nancy

Nancy, 54500, France

Location

CHU Nantes

Nantes, 44093, France

Location

CHU Nice

Nice, 06002, France

Location

Clinique St Georges

Nice, 06100, France

Location

AP-HP La Salpêtrière

Paris, 75013, France

Location

AURA Paris 14ème

Paris, 75014, France

Location

AURA Paris Plaisance

Paris, 75014, France

Location

Hôpital Tenon

Paris, 75020, France

Location

AP-HP Necker

Paris, 75743, France

Location

Institut Mutualiste Montsouris

Paris, France

Location

CHU Lyon Sud

Pierre-Bénite, 69495, France

Location

CHU de Reims

Reims, 51100, France

Location

ARPDD Reims

Reims, 51726, France

Location

CHU Rennes

Rennes, 35000, France

Location

ECHO Confluent

Rezé, 44402, France

Location

Centre de Perharidy

Roscoff, 29260, France

Location

CH Roubaix

Roubaix, 59056, France

Location

CHG St Brieuc

Saint-Brieuc, 22000, France

Location

CHU de la Réunion Hôpital Félix Guyon

Saint-Denis, 97405, France

Location

Aub Saint Malo

St-Malo, 35400, France

Location

Ch Saint Malo

St-Malo, 35403, France

Location

AURAL St Anne (AURAL Strasbourg)

Strasbourg, 67000, France

Location

CHU Strasbourg

Strasbourg, 67000, France

Location

Clinique Sainte Anne

Strasbourg, 67000, France

Location

AURAL Strasbourg

Strasbourg, 67200, France

Location

CHU Toulouse

Toulouse, 31059, France

Location

CHU Tours

Tours, 37000, France

Location

CH Troyes

Troyes, 10003, France

Location

CH Valenciennes

Valenciennes, 59322, France

Location

ALTIR Nancy

Vandœuvre-lès-Nancy, 54504, France

Location

Hôpitaux Privés de Metz- Hôpital Robert Schuman

Vantoux, 57070, France

Location

CH Verdun

Verdun, 55107, France

Location

CH Vichy

Vichy, 03201, France

Location

CH Princesse Grace

Monaco, Monaco

Location

Related Publications (2)

  • Rossignol P, Zannad F, Massy Z, Azizi M, Chorfa F, Coadic J, Ferreira JP, Saraiva F, Mottier D, Guillemin F, Ngueyon Sime W, Bouali S, Rossignol B, Nortier J, Simon I, Robino C, Davin M, Bataille PM, Chantrel F, Castin N, Esnault V, Kazes I, Hannedouche T, Kamar N, Achard JM, Fenerol C, Achard-Hottelart C, Dimitrov Y, Girerd N, Maucort-Boulch D, Frimat L; ALCHEMIST study group. Spironolactone in patients on chronic haemodialysis at high risk of adverse cardiovascular outcomes (ALCHEMIST): a multicentre, double-blind, randomised, placebo-controlled trial and updated meta-analysis. Lancet. 2025 Aug 16;406(10504):705-718. doi: 10.1016/S0140-6736(25)01194-8.

  • 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.

MeSH Terms

Conditions

Renal Insufficiency, ChronicKidney Failure, Chronic

Interventions

Spironolactone

Condition Hierarchy (Ancestors)

Renal InsufficiencyKidney DiseasesUrologic DiseasesFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

LactonesOrganic ChemicalsPregnenesPregnanesSteroidsFused-Ring CompoundsPolycyclic Compounds

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 3, 2013

First Posted

May 7, 2013

Study Start

June 1, 2013

Primary Completion

November 1, 2022

Study Completion

November 1, 2022

Last Updated

October 10, 2023

Record last verified: 2023-10

Data Sharing

IPD Sharing
Will share

Statistical Analysis Plan

Shared Documents
SAP
More information

Locations