ALdosterone Antagonist Chronic HEModialysis Interventional Survival Trial
- Conditions
- End Stage Renal Failure on Dialysis
- Interventions
- Drug: Placebo
- Registration Number
- NCT01848639
- Lead Sponsor
- University Hospital, Brest
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 823
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Spironolactone 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. Placebo 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.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method Determine the effects of spironolactone compared to placebo on the composite winratio endpoint 24 months 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.non-cardiovascular mortality rate 24 months Additional secondary objectives will be considered in the context of hypothesis generation
cumulative accident rates forming the primary endpoint 24 months Additional secondary objectives will be considered in the context of hypothesis generation
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 Additional secondary objectives will be considered in the context of hypothesis generation
Incidence of procedures related to stenosis or vascular access thrombosis for hemodialysis (HD) 24 months Additional secondary objectives will be considered in the context of hypothesis generation
Incidence of coronary or peripheral revascularizations (including lower limb amputations) 24 months Additional secondary objectives will be considered in the context of hypothesis generation
Blood pressure (systolic and diastolic pressure) 24 months Additional secondary objectives will be considered in the context of hypothesis generation
Blood pressure's variability inter visit (systolic and diastolic pressure) 24 months Additional secondary objectives will be considered in the context of hypothesis generation
The occurrence of atrial fibrillation 24 months Additional secondary objectives will be considered in the context of hypothesis generation
Incidence of hyperkalemia> 6 mmol/l 24 months Additional secondary objectives will be considered in the context of hypothesis generation
Estimation of the effect of treatment on quality of life. 24 months SF36 questionnaire ; minimum value = 0 ; maximum value = 100 ; higher score means a better outcome
Trial Locations
- Locations (70)
Clinique Bouchard
🇫🇷Marseille, France
CHU Caen
🇫🇷Caen, France
CH Avignon
🇫🇷Avignon, France
AURA Paris Plaisance
🇫🇷Paris, France
ALTIR Metz
🇫🇷Metz, France
CH Cahors
🇫🇷Cahors, France
Hôpital Erasme- Bruxelles
🇧🇪Bruxelles, Belgium
CH Ardeche Nord
🇫🇷Annonay, Ardeche, France
CHU Besançon
🇫🇷Besançon, France
CHRU Brest
🇫🇷Brest, France
APHP Henri Mondor
🇫🇷Créteil, France
AURAL Colmar
🇫🇷Colmar, France
AURAL Mulhouse
🇫🇷Mulhouse, France
CHR Metz-Thionville
🇫🇷Metz, France
CHU Nice
🇫🇷Nice, France
CHU Tours
🇫🇷Tours, France
Ch Saint Malo
🇫🇷Saint-Malo, France
Aub Saint Malo
🇫🇷Saint Malo, France
CHG St Brieuc
🇫🇷St Brieuc, France
CHU de la Réunion Hôpital Félix Guyon
🇫🇷Saint Denis, France
CHU de Lyon
🇫🇷Lyon, France
La Roche Sur Yon
🇫🇷La Roche Sur Yon, France
AURAL Lyon
🇫🇷Lyon, France
Hopitaux Civils de Colmar
🇫🇷Colmar, France
CHPC Cherbourg
🇫🇷Cherbourg, France
Polyclinique de Lagny
🇫🇷Lagny, France
AGDUC Grenoble
🇫🇷Grenoble, France
AURAL Haguenau
🇫🇷Haguenau, France
Adpc Marseille
🇫🇷Marseille, France
APHM Marseille
🇫🇷Marseille, France
CH Mulhouse
🇫🇷Mulhouse, France
AURA Paris 14ème
🇫🇷Paris, France
AP-HP Necker
🇫🇷Paris, France
Clinique St Georges
🇫🇷Nice, France
Institut Mutualiste Montsouris
🇫🇷Paris, France
CHU Lyon Sud
🇫🇷Pierre-Bénite, France
CHU de Reims
🇫🇷Reims, France
ARPDD Reims
🇫🇷Reims, France
Centre de Perharidy
🇫🇷Roscoff, France
CH Roubaix
🇫🇷Roubaix, France
CHU Strasbourg
🇫🇷Strasbourg, France
CHU Toulouse
🇫🇷Toulouse, France
CH Valenciennes
🇫🇷Valenciennes, France
Hôpitaux Privés de Metz- Hôpital Robert Schuman
🇫🇷Vantoux, France
CHU Amiens
🇫🇷Amiens, France
CH Boulogne Sur Mer
🇫🇷Boulogne Sur Mer, France
CH Chambéry
🇫🇷Chambéry, France
CHU Dijon Hôpital du Bocage
🇫🇷Dijon, France
CH Haguenau
🇫🇷Haguenau, France
Clinique Lille
🇫🇷Lille, France
CHU Lille
🇫🇷Lille, France
CHU Limoges
🇫🇷Limoges, France
AURAL La Croix Rousse
🇫🇷Lyon, France
ALURAD Limoges
🇫🇷Limoges, France
Association de Metz
🇫🇷Metz, France
CH St Joseph-St Luc
🇫🇷Lyon, France
AP-HP La Salpêtrière
🇫🇷Paris, France
CHU Nancy
🇫🇷Nancy, France
CHU Nantes
🇫🇷Nantes, France
Hôpital Tenon
🇫🇷Paris, France
ECHO Confluent
🇫🇷Reze, France
CHU Rennes
🇫🇷Rennes, France
CH Troyes
🇫🇷Troyes, France
AURAL St Anne (AURAL Strasbourg)
🇫🇷Strasbourg, France
Clinique Sainte Anne
🇫🇷Strasbourg, France
ALTIR Nancy
🇫🇷Vandoeuvre les Nancy, France
AURAL Strasbourg
🇫🇷Strasbourg, France
CH Verdun
🇫🇷Verdun, France
CH Princesse Grace
🇲🇨Monaco, Monaco
CH Vichy
🇫🇷Vichy, France