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End Stage Renal Failure on DialysisPhase 3ALCHEMISTNCT01848639

ALdosterone Antagonist Chronic HEModialysis Interventional Survival Trial

A Phase 3 study testing Spironolactone in people with End Stage Renal Failure on Dialysis, run by University Hospital, Brest at 70 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
End Stage Renal Failure on Dialysis
What is being tested?
Spironolactone
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
823 participants
Where
70 sitesin 3 countries
Study dates
Jun 2013to Nov 2022
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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%
Show all 10Show fewer
  • OR large QRS > 0.14 sec
  • OR Left bundle branch block (ECG) measured during the twelve months preceding inclusion; diabetes;
  • 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

Who cannot join

  • 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
Show all 24Show fewer
  • kidney transplant scheduled within the year
  • symptomatic interdialytic hypotension
  • acute systemic disease
  • uncompensated hypothyroidism
  • acute hyperthyroidism
  • any prior or concomitant clinical condition compromising the inclusion, in the discretion of the investigator
  • cardiac transplant
  • severe uncontrolled arrhythmia
  • stroke within 3 months prior to enrolment
  • acute coronary syndrome in the previous month inclusion
  • recent (1 month) or planned coronary revascularization by angioplasty
  • recent (3 months) or planned cardiovascular surgery (excluding HD vascular access)
  • non menopausal women or without effective contraceptive methods
  • pregnancy, breastfeeding or planning a pregnancy within 2 years
  • non compliance
  • protected adult
  • SBP > 200 mmHg and/or DBP > 110 mmHg
  • Concomitant treatment can not be stopped by another potassium-sparing diuretic, a potassium supplements, AINS or Cox 2 inhibitors

Trial locations and contacts

70 sites in 3 countries.

70 sites in 3 countries

France68 sites

  • CHU Amiens

    Amiens, 80054

  • CH Ardeche Nord

    Annonay, Ardeche, 07100

  • CH Avignon

    Avignon, 84000

  • CHU Besançon

    Besançon, 25000

  • CH Boulogne Sur Mer

    Boulogne-sur-Mer, 62321

  • CHRU Brest

    Brest, 29609

  • CHU Caen

    Caen, 14033

  • CH Cahors

    Cahors, 46000

  • CH Chambéry

    Chambéry, 73000

  • CHPC Cherbourg

    Cherbourg, 50100

  • AURAL Colmar

    Colmar, 68000

  • Hopitaux Civils de Colmar

    Colmar, 68024

  • APHP Henri Mondor

    Créteil, 94010

  • CHU Dijon Hôpital du Bocage

    Dijon, 21079

  • AGDUC Grenoble

    Grenoble, 38043

  • AURAL Haguenau

    Haguenau, 67500

  • CH Haguenau

    Haguenau, 67500

  • La Roche Sur Yon

    La Roche-sur-Yon, 85000

  • Polyclinique de Lagny

    Lagny, 77400

  • Clinique Lille

    Lille, 59000

  • CHU Lille

    Lille, 59037

  • ALURAD Limoges

    Limoges, 87000

  • CHU Limoges

    Limoges, 87042

  • CHU de Lyon

    Lyon, 69003

  • AURAL La Croix Rousse

    Lyon, 69004

  • CH St Joseph-St Luc

    Lyon, 69007

  • AURAL Lyon

    Lyon, 69008

  • Clinique Bouchard

    Marseille, 13006

  • Adpc Marseille

    Marseille, 13009

  • APHM Marseille

    Marseille, 13385

  • Association de Metz

    Metz, 57000

  • ALTIR Metz

    Metz, 58085

  • CHR Metz-Thionville

    Metz, 58085

  • AURAL Mulhouse

    Mulhouse, 68100

  • CH Mulhouse

    Mulhouse, 68100

  • CHU Nancy

    Nancy, 54500

  • CHU Nantes

    Nantes, 44093

  • CHU Nice

    Nice, 06002

  • Clinique St Georges

    Nice, 06100

  • AP-HP La Salpêtrière

    Paris, 75013

  • AURA Paris 14ème

    Paris, 75014

  • AURA Paris Plaisance

    Paris, 75014

  • Hôpital Tenon

    Paris, 75020

  • AP-HP Necker

    Paris, 75743

  • Institut Mutualiste Montsouris

    Paris

  • CHU Lyon Sud

    Pierre-Bénite, 69495

  • CHU de Reims

    Reims, 51100

  • ARPDD Reims

    Reims, 51726

  • CHU Rennes

    Rennes, 35000

  • ECHO Confluent

    Rezé, 44402

  • Centre de Perharidy

    Roscoff, 29260

  • CH Roubaix

    Roubaix, 59056

  • CHG St Brieuc

    Saint-Brieuc, 22000

  • CHU de la Réunion Hôpital Félix Guyon

    Saint-Denis, 97405

  • Aub Saint Malo

    St-Malo, 35400

  • Ch Saint Malo

    St-Malo, 35403

  • AURAL St Anne (AURAL Strasbourg)

    Strasbourg, 67000

  • CHU Strasbourg

    Strasbourg, 67000

  • Clinique Sainte Anne

    Strasbourg, 67000

  • AURAL Strasbourg

    Strasbourg, 67200

  • CHU Toulouse

    Toulouse, 31059

  • CHU Tours

    Tours, 37000

  • CH Troyes

    Troyes, 10003

  • CH Valenciennes

    Valenciennes, 59322

  • ALTIR Nancy

    Vandœuvre-lès-Nancy, 54504

  • Hôpitaux Privés de Metz- Hôpital Robert Schuman

    Vantoux, 57070

  • CH Verdun

    Verdun, 55107

  • CH Vichy

    Vichy, 03201

Other trials in France

Belgium1 site

  • Hôpital Erasme- Bruxelles

    Brussels, 1070

Other trials in Belgium

Monaco1 site

  • CH Princesse Grace

    Monaco

Other trials in Monaco

About this study

Official title: ALdosterone Antagonist Chronic HEModialysis Interventional Survival Trial (ALCHEMIST), Phase III b

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.

Read the detailed description
  • During a run-in period : Spironolactone will be initially administered per os at a 25 mg dose per two days in practice after the session, three times per week
  • Patients will be randomized (spironolactone vs. placebo) and titrated over one month to a maximum single dose of 25 mg/d
  • However if kalemia is greater than or equal to 5.5 mmol / l twice on this run-in period or on the day of randomization, patient won't be randomized.
  • A pre-specified algorithm for the management of the risk of incident hyperkalemia will be followed, including dose adjustment, temporary cessation of study treatment, in addition to usual dietary measures and the use of chelating resins and low-potassium dialysis baths
  • Patients will be followed for a mean of 2 years.
Being tested
Spironolactone, Placebo
Keywords
chronic kidney disease, end-stage renal disease, hemodialysis (ESRD), cardiovascular morbimortality, aldosterone antagonist, spironolactone
Medical subject headings
Renal Insufficiency, Chronic, Kidney Failure, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SpironolactoneDrug

    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.

  • PlaceboDrug

    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.

Study groups in NCT01848639
Study groupRoleWhat they receive
SpironolactoneActive comparatorAfter 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.
Receives: Drug: Spironolactone
PlaceboPlacebo comparatorAfter 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.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 25 months

Secondary outcomes (14)

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

    Following a hierarchical strategy of statistical tests including the primary endpoint.

    Composite winratio endpoint of: all-cause mortality at 2 years according to the Finkelstein and Schoenfeld method.

    Measured: 24 months

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

    Following a hierarchical strategy of statistical tests including the primary endpoint.

    Composite winratio endpoint of: time until a cardiovascular event (hospitalization for heart failure, or non-fatal myocardial infarction, or acute coronary syndrome or non-fatal stroke) at 2 years according to the Finkelstein and Schoenfeld method.

    Measured: 24 months

  3. non-cardiovascular mortality rate

    Additional secondary objectives will be considered in the context of hypothesis generation

    Measured: 24 months

  4. cumulative accident rates forming the primary endpoint

    Additional secondary objectives will be considered in the context of hypothesis generation

    Measured: 24 months

  5. 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)

    Additional secondary objectives will be considered in the context of hypothesis generation

    Measured: 24 months

  6. Incidence of procedures related to stenosis or vascular access thrombosis for hemodialysis (HD)

    Additional secondary objectives will be considered in the context of hypothesis generation

    Measured: 24 months

  7. Incidence of coronary or peripheral revascularizations (including lower limb amputations)

    Additional secondary objectives will be considered in the context of hypothesis generation

    Measured: 24 months

  8. Blood pressure (systolic and diastolic pressure)

    Additional secondary objectives will be considered in the context of hypothesis generation

    Measured: 24 months

  9. Blood pressure's variability inter visit (systolic and diastolic pressure)

    Additional secondary objectives will be considered in the context of hypothesis generation

    Measured: 24 months

  10. The occurrence of atrial fibrillation

    Additional secondary objectives will be considered in the context of hypothesis generation

    Measured: 24 months

  11. Incidence of hyperkalemia> 6 mmol/l

    Additional secondary objectives will be considered in the context of hypothesis generation

    Measured: 24 months

  12. Estimation of the effect of treatment on quality of life.

    KDQoL questionnaire ; minimum value = 0 ; maximum value = 100 ; higher score means a better outcome

    Measured: 24 months

  13. Estimation of the effect of treatment on quality of life.

    Minnesota questionnaire ; minimum value = 0 ; maximum value = 100 ; higher score means a better outcome

    Measured: 24 months

  14. Estimation of the effect of treatment on quality of life.

    SF36 questionnaire ; minimum value = 0 ; maximum value = 100 ; higher score means a better outcome

    Measured: 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 May 2013 (estimated)
  2. Study startJun 2013
  3. Primary completionNov 2022
  4. Study completionNov 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
823 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01848639
Sponsor's protocol ID
ALCHEMIST
Other IDs
RB 12-079
Acronym
ALCHEMIST
Status last verified
Oct 2023
First submitted
3 May 2013
Last updated
10 Oct 2023
Results posted
No
Data monitoring committee
Yes
Individual data sharing
Yes: Statistical Analysis Plan

Publications

  • 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.

    PubMed 40818851

  • 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.

    PubMed 33586138

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Spironolactone in people with End Stage Renal Failure on Dialysis, run by University Hospital, Brest at 70 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 70 sites in France, Belgium, Monaco. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: 25 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01848639, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Oct 2023.

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