ALdosterone Antagonist Chronic HEModialysis Interventional Survival Trial (ALCHEMIST), Phase III b
Overview
- Phase
- Phase 3
- Intervention
- Spironolactone
- Conditions
- End Stage Renal Failure on Dialysis
- Sponsor
- University Hospital, Brest
- Enrollment
- 823
- Locations
- 70
- Primary Endpoint
- 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
- Status
- Completed
- Last Updated
- 2 years ago
Overview
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.
Investigators
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
Arms & 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: Spironolactone
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: Placebo
Outcomes
Primary Outcomes
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
- 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)
- Incidence of procedures related to stenosis or vascular access thrombosis for hemodialysis (HD)(24 months)
- Incidence of coronary or peripheral revascularizations (including lower limb amputations)(24 months)
- Blood pressure (systolic and diastolic pressure)(24 months)
- Blood pressure's variability inter visit (systolic and diastolic pressure)(24 months)
- The occurrence of atrial fibrillation(24 months)
- Incidence of hyperkalemia> 6 mmol/l(24 months)
- Estimation of the effect of treatment on quality of life.(24 months)