ALdosterone Antagonist Chronic HEModialysis Interventional Survival Trial

NCT ID: NCT01848639

Last Updated: 2023-10-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 823 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-06-30
• Study Completion Date: 2022-11-30

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.

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.

Conditions

End Stage Renal Failure on Dialysis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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 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.

Group Type: ACTIVE_COMPARATOR

Spironolactone

Intervention Type: DRUG

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.

Placebo

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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.

Interventions

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 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.

Intervention Type: DRUG

Placebo

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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 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

Exclusion Criteria

• 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
• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Central Hospital, Nancy, France

OTHER

Sponsor Role: collaborator

Institut National de la Santé Et de la Recherche Médicale, France

OTHER_GOV

Sponsor Role: collaborator

University Hospital, Brest

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Hôpital Erasme- Bruxelles

Brussels, , Belgium

CH Ardeche Nord

Annonay, Ardeche, France

CHU Amiens

Amiens, , France

CH Avignon

Avignon, , France

CHU Besançon

Besançon, , France

CH Boulogne Sur Mer

Boulogne-sur-Mer, , France

CHRU Brest

Brest, , France

CHU Caen

Caen, , France

CH Cahors

Cahors, , France

CH Chambéry

Chambéry, , France

CHPC Cherbourg

Cherbourg, , France

AURAL Colmar

Colmar, , France

Hopitaux Civils de Colmar

Colmar, , France

APHP Henri Mondor

Créteil, , France

CHU Dijon Hôpital du Bocage

Dijon, , France

AGDUC Grenoble

Grenoble, , France

AURAL Haguenau

Haguenau, , France

CH Haguenau

Haguenau, , France

La Roche Sur Yon

La Roche-sur-Yon, , France

Polyclinique de Lagny

Lagny, , France

Clinique Lille

Lille, , France

CHU Lille

Lille, , France

ALURAD Limoges

Limoges, , France

CHU Limoges

Limoges, , France

CHU de Lyon

Lyon, , France

AURAL La Croix Rousse

Lyon, , France

CH St Joseph-St Luc

Lyon, , France

AURAL Lyon

Lyon, , France

Clinique Bouchard

Marseille, , France

Adpc Marseille

Marseille, , France

APHM Marseille

Marseille, , France

Association de Metz

Metz, , France

ALTIR Metz

Metz, , France

CHR Metz-Thionville

Metz, , France

AURAL Mulhouse

Mulhouse, , France

CH Mulhouse

Mulhouse, , France

CHU Nancy

Nancy, , France

CHU Nantes

Nantes, , France

CHU Nice

Nice, , France

Clinique St Georges

Nice, , France

AP-HP La Salpêtrière

Paris, , France

AURA Paris 14ème

Paris, , France

AURA Paris Plaisance

Paris, , France

Hôpital Tenon

Paris, , France

AP-HP Necker

Paris, , France

Institut Mutualiste Montsouris

Paris, , France

CHU Lyon Sud

Pierre-Bénite, , France

CHU de Reims

Reims, , France

ARPDD Reims

Reims, , France

CHU Rennes

Rennes, , France

ECHO Confluent

Rezé, , France

Centre de Perharidy

Roscoff, , France

CH Roubaix

Roubaix, , France

CHG St Brieuc

Saint-Brieuc, , France

CHU de la Réunion Hôpital Félix Guyon

Saint-Denis, , France

Aub Saint Malo

St-Malo, , France

Ch Saint Malo

St-Malo, , France

AURAL St Anne (AURAL Strasbourg)

Strasbourg, , France

CHU Strasbourg

Strasbourg, , France

Clinique Sainte Anne

Strasbourg, , France

AURAL Strasbourg

Strasbourg, , France

CHU Toulouse

Toulouse, , France

CHU Tours

Tours, , France

CH Troyes

Troyes, , France

CH Valenciennes

Valenciennes, , France

ALTIR Nancy

Vandœuvre-lès-Nancy, , France

Hôpitaux Privés de Metz- Hôpital Robert Schuman

Vantoux, , France

CH Verdun

Verdun, , France

CH Vichy

Vichy, , France

CH Princesse Grace

Monaco, , Monaco

Countries

Belgium; France; Monaco

References

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, Maucourt-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.

Reference Type: DERIVED

PMID: 40818851 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33586138 (View on PubMed)

Other Identifiers

RB 12-079

Identifier Type: OTHER

Identifier Source: secondary_id

ALCHEMIST

Identifier Type: -

Identifier Source: org_study_id