CClinicalTrials.gg
CompletedNCT01848639ALCHEMISTUpdated Oct 10, 2023

ALdosterone Antagonist Chronic HEModialysis Interventional Survival Trial

A Phase 3 interventional study of Spironolactone and Placebo in End Stage Renal Failure on Dialysis, sponsored by University Hospital, Brest. Completed at 70 sites in 3 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-10-10.

Sponsored by University Hospital, Brest · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
823
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

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.
02

Conditions studied

  • End Stage Renal Failure on Dialysis

Keywords

  • chronic kidney disease
  • end-stage renal disease
  • hemodialysis (ESRD)
  • cardiovascular morbimortality
  • aldosterone antagonist
  • spironolactone
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
823 participants (actual)

Study arms

  • Active comparator
    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.

    Drug: Spironolactone

  • Placebo comparator
    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.

    Drug: Placebo

Interventions

  • DrugSpironolactone

    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.

  • DrugPlacebo

    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.

05

What researchers measure

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

    Time frame: 25 months

Secondary outcomes

  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.

    Time frame: 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.

    Time frame: 24 months

  3. non-cardiovascular mortality rate

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

    Time frame: 24 months

  4. cumulative accident rates forming the primary endpoint

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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 24 months

  8. Blood pressure (systolic and diastolic pressure)

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

    Time frame: 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

    Time frame: 24 months

  10. The occurrence of atrial fibrillation

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

    Time frame: 24 months

  11. Incidence of hyperkalemia> 6 mmol/l

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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 24 months

Other outcomes

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

    Time frame: 24 months

  2. Ancillary study:morbimortality data

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

06

Study locations

70 sites
  • Hôpital Erasme- Bruxelles
    Bruxelles, 1070, Belgium
  • CH Ardeche Nord
    Annonay, Ardeche 07100, France
  • CHU Amiens
    Amiens, 80054, France
  • CH Avignon
    Avignon, 84000, France
  • CHU Besançon
    Besançon, 25000, France
  • CH Boulogne Sur Mer
    Boulogne Sur Mer, 62321, France
  • CHRU Brest
    Brest, 29609, France
  • CHU Caen
    Caen, 14033, France
  • CH Cahors
    Cahors, 46000, France
  • CH Chambéry
    Chambéry, 73000, France
  • CHPC Cherbourg
    Cherbourg, 50100, France
  • AURAL Colmar
    Colmar, 68000, France
  • Hopitaux Civils de Colmar
    Colmar, 68024, France
  • APHP Henri Mondor
    Créteil, 94010, France
  • CHU Dijon Hôpital du Bocage
    Dijon, 21079, France
  • AGDUC Grenoble
    Grenoble, 38043, France
  • AURAL Haguenau
    Haguenau, 67500, France
  • CH Haguenau
    Haguenau, 67500, France
  • La Roche Sur Yon
    La Roche Sur Yon, 85000, France
  • Polyclinique de Lagny
    Lagny, 77400, France
  • Clinique Lille
    Lille, 59000, France
  • CHU Lille
    Lille, 59037, France
  • ALURAD Limoges
    Limoges, 87000, France
  • CHU Limoges
    Limoges, 87042, France
  • CHU de Lyon
    Lyon, 69003, France
  • AURAL La Croix Rousse
    Lyon, 69004, France
  • CH St Joseph-St Luc
    Lyon, 69007, France
  • AURAL Lyon
    Lyon, 69008, France
  • Clinique Bouchard
    Marseille, 13006, France
  • Adpc Marseille
    Marseille, 13009, France
  • APHM Marseille
    Marseille, 13385, France
  • Association de Metz
    Metz, 57000, France
  • ALTIR Metz
    Metz, 58085, France
  • CHR Metz-Thionville
    Metz, 58085, France
  • AURAL Mulhouse
    Mulhouse, 68100, France
  • CH Mulhouse
    Mulhouse, 68100, France
  • CHU Nancy
    Nancy, 54500, France
  • CHU Nantes
    Nantes, 44093, France
  • CHU Nice
    Nice, 06002, France
  • Clinique St Georges
    Nice, 06100, France
  • AP-HP La Salpêtrière
    Paris, 75013, France
  • AURA Paris 14ème
    Paris, 75014, France
  • AURA Paris Plaisance
    Paris, 75014, France
  • Hôpital Tenon
    Paris, 75020, France
  • AP-HP Necker
    Paris, 75743, France
  • Institut Mutualiste Montsouris
    Paris, France
  • CHU Lyon Sud
    Pierre-Bénite, 69495, France
  • CHU de Reims
    Reims, 51100, France
  • ARPDD Reims
    Reims, 51726, France
  • CHU Rennes
    Rennes, 35000, France
  • ECHO Confluent
    Reze, 44402, France
  • Centre de Perharidy
    Roscoff, 29260, France
  • CH Roubaix
    Roubaix, 59056, France
  • CHU de la Réunion Hôpital Félix Guyon
    Saint Denis, 97405, France
  • Aub Saint Malo
    Saint Malo, 35400, France
  • Ch Saint Malo
    Saint-Malo, 35403, France
  • CHG St Brieuc
    St Brieuc, 22000, France
  • AURAL St Anne (AURAL Strasbourg)
    Strasbourg, 67000, France
  • CHU Strasbourg
    Strasbourg, 67000, France
  • Clinique Sainte Anne
    Strasbourg, 67000, France
  • AURAL Strasbourg
    Strasbourg, 67200, France
  • CHU Toulouse
    Toulouse, 31059, France
  • CHU Tours
    Tours, 37000, France
  • CH Troyes
    Troyes, 10003, France
  • CH Valenciennes
    Valenciennes, 59322, France
  • ALTIR Nancy
    Vandoeuvre les Nancy, 54504, France
  • Hôpitaux Privés de Metz- Hôpital Robert Schuman
    Vantoux, 57070, France
  • CH Verdun
    Verdun, 55107, France
  • CH Vichy
    Vichy, 03201, France
  • CH Princesse Grace
    Monaco, Monaco
07

References and documents

Publications

  • 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 ↗

Individual participant data

Plan to share: Yes — Statistical Analysis Plan

Supporting information: Sap

08

Registry details

Key details

Study ID
NCT01848639
Lead sponsor
University Hospital, Brest
Collaborators
Central Hospital, Nancy, France, Institut National de la Santé Et de la Recherche Médicale, France
Responsible party
Sponsor
First posted
May 7, 2013
Start date
Jun 2013
Primary completion
Nov 2022
Completion
Nov 2022
Last update
Oct 10, 2023

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Oct 2023. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Start the discussion