ALdosterone Antagonist Chronic HEModialysis Interventional Survival Trial (ALCHEMIST)
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| ClinicalTrials.gov Identifier: NCT01848639 |
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Recruitment Status :
Active, not recruiting
First Posted : May 7, 2013
Last Update Posted : November 23, 2022
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Sponsor:
University Hospital, Brest
Collaborators:
Central Hospital, Nancy, France
Institut National de la Santé Et de la Recherche Médicale, France
Information provided by (Responsible Party):
University Hospital, Brest
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| End Stage Renal Failure on Dialysis | Drug: Spironolactone Drug: Placebo | Phase 3 |
- 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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 825 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Triple (Participant, Care Provider, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | ALdosterone Antagonist Chronic HEModialysis Interventional Survival Trial (ALCHEMIST), Phase III b |
| Actual Study Start Date : | June 2013 |
| Estimated Primary Completion Date : | November 2022 |
| Estimated Study Completion Date : | November 2022 |
Resource links provided by the National Library of Medicine
MedlinePlus related topics:
Dialysis
Drug Information available for:
Spironolactone
| Arm | Intervention/treatment |
|---|---|
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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.
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Drug: 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. |
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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
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 :
- 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 Outcome Measures :
- composite winratio endpoint of: all-cause mortality [ Time Frame: 25 months ]
- composite winratio endpoint of: time until a cardiovascular event [ Time Frame: 25 months ]cardiovascular event : hospitalization for heart failure, or non-fatal myocardial infarction, or acute coronary syndrome or non-fatal stroke
- 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) [ Time Frame: 25 months ]
- Incidence of procedures related to stenosis or vascular access thrombosis for hemodialysis (HD) [ Time Frame: 25 months ]
- Incidence of coronary or peripheral revascularizations (including lower limb amputations) [ Time Frame: 25 months ]
- Blood pressure and its inter visit variability [ Time Frame: 25 months ]
- The occurrence of atrial fibrillation [ Time Frame: 25 months ]
- Incidence of hyperkalemia> 6 mmol/l [ Time Frame: 25 months ]
- Estimation of the effect of treatment on quality of life. [ Time Frame: 25 months ]
Other Outcome Measures:
- Ancillary study:establishment of a biological collection (serum bank and DNA biobank) for future biomarker studies [ Time Frame: 25 months ]
- Ancillary study:morbimortality data [ Time Frame: 3, 5 and 10 years of follow-up after the double-blind study ]
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01848639
Locations
Show 70 study locations
Sponsors and Collaborators
University Hospital, Brest
Central Hospital, Nancy, France
Institut National de la Santé Et de la Recherche Médicale, France
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | University Hospital, Brest |
| ClinicalTrials.gov Identifier: | NCT01848639 |
| Other Study ID Numbers: |
ALCHEMIST RB 12-079 ( Other Identifier: CHRU Brest ) |
| First Posted: | May 7, 2013 Key Record Dates |
| Last Update Posted: | November 23, 2022 |
| Last Verified: | November 2022 |
Keywords provided by University Hospital, Brest:
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chronic kidney disease end-stage renal disease hemodialysis (ESRD) |
cardiovascular morbimortality aldosterone antagonist spironolactone |
Additional relevant MeSH terms:
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Kidney Failure, Chronic Renal Insufficiency Kidney Diseases Urologic Diseases Renal Insufficiency, Chronic Spironolactone Mineralocorticoid Receptor Antagonists |
Hormone Antagonists Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Diuretics, Potassium Sparing Diuretics Natriuretic Agents |