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ALdosterone Antagonist Chronic HEModialysis Interventional Survival Trial (ALCHEMIST)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by University Hospital, Brest
Sponsor:
Collaborators:
Central Hospital, Nancy, France
Institut National de la Santé Et de la Recherche Médicale, France
Information provided by (Responsible Party):
University Hospital, Brest
ClinicalTrials.gov Identifier:
NCT01848639
First received: May 3, 2013
Last updated: July 30, 2014
Last verified: July 2014
  Purpose

This study is designed to determine the effects of spironolactone in comparison to placebo on the composite endpoint of nonfatal Myocardial Infarction (MI), hospitalization for heart failure, nonfatal stroke or cardiovascular-induced death. The primary endpoint will be the time to onset of the first incident.


Condition Intervention Phase
End Stage Renal Failure on Dialysis
Drug: Spironolactone
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: ALdosterone Antagonist Chronic HEModialysis Interventional Survival Trial (ALCHEMIST), Phase III b

Resource links provided by NLM:


Further study details as provided by University Hospital, Brest:

Primary Outcome Measures:
  • The time to onset of the first incident :non-fatal MI or hospitalization for heart failure or nonfatal stroke or cardiovascular (CV) death [ Time Frame: 25 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • The cumulate rate of nonfatal MI, hospitalization for heart failure, nonfatal stroke or CV death [ Time Frame: 25 months ] [ Designated as safety issue: Yes ]
  • The time to onset of death from i) any cause and ii) from a CV event and iii) from a non CV cause [ Time Frame: 25 months ] [ Designated as safety issue: Yes ]
  • The time of survival without a major CV event (nonfatal MI, hospitalization for heart failure, non-fatal stroke, cardiac arrest resuscitation) [ Time Frame: 25 months ] [ Designated as safety issue: Yes ]
  • Incidence of procedures related to stenosis or vascular access thrombosis for hemodialysis (HD) [ Time Frame: 25 months ] [ Designated as safety issue: Yes ]
  • Incidence of coronary or peripheral revascularizations (including lower limb amputations) [ Time Frame: 25 months ] [ Designated as safety issue: Yes ]
  • Blood pressure and its inter visit variability [ Time Frame: 25 months ] [ Designated as safety issue: Yes ]
  • The occurrence of atrial fibrillation [ Time Frame: 25 months ] [ Designated as safety issue: Yes ]
  • Incidence of hyperkalemia> 6 mmol/l [ Time Frame: 25 months ] [ Designated as safety issue: Yes ]
  • Estimation of the effect of treatment on quality of life. [ Time Frame: 25 months ] [ Designated as safety issue: Yes ]

Other Outcome Measures:
  • Ancillary study:establishment of a biological collection (serum bank and DNA biobank) for future biomarker studies [ Time Frame: 25 months ] [ Designated as safety issue: No ]
  • Ancillary study:morbimortality data [ Time Frame: 3, 5 and 10 years of follow-up after the double-blind study ] [ Designated as safety issue: No ]

Estimated Enrollment: 825
Study Start Date: June 2013
Estimated Study Completion Date: June 2018
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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 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.

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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent
  • Health insurance beneficiary
  • Men and women, on hemodialysis for at least 6 months for end-stage renal disease regardless of the aetiology including diabetes, with at least 3 hemodialysis sessions per week AND presenting at least one of following comorbidities or CV risk factors:
  • left ventricular mass > 130 g/m2 in men and 100 g/m2 in women measured during the twelve months preceding inclusion
  • left ventricular ejection fraction < 40% measured during the twelve months preceding inclusion
  • diabetes
  • history of Cardiovascular disease: coronary artery disease, symptomatic lower limb peripheral arterial disease, carotid or renal artery stenosis > 50%, stroke, hospitalization for heart failure.

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
  • co-morbidity with life-threatening prognosis established at 2 years
  • cardiac transplant
  • severe uncontrolled arrhythmia
  • stroke or acute coronary syndrome within 3 months prior to enrolment
  • recent (3 months) or planned coronary revascularization or 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 or significant clinico-biological abnormalities not directly related to ESRD
  • Concomitant treatment can not be stopped by another potassium-sparing diuretic, a potassium supplements, AINS or Cox 2 inhibitors
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01848639

Contacts
Contact: Patrick ROSSIGNOL, Pr +33383157320 p.rossignol@chu-nancy.fr

  Show 49 Study Locations
Sponsors and Collaborators
University Hospital, Brest
Central Hospital, Nancy, France
Institut National de la Santé Et de la Recherche Médicale, France
  More Information

No publications provided

Responsible Party: University Hospital, Brest
ClinicalTrials.gov Identifier: NCT01848639     History of Changes
Other Study ID Numbers: ALCHEMIST, RB 12-079
Study First Received: May 3, 2013
Last Updated: July 30, 2014
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé

Keywords provided by University Hospital, Brest:
chronic kidney disease
end-stage renal disease
hemodialysis (ESRD)
cardiovascular morbimortality
aldosterone antagonist
spironolactone

Additional relevant MeSH terms:
Kidney Failure, Chronic
Renal Insufficiency
Kidney Diseases
Renal Insufficiency, Chronic
Urologic Diseases
Mineralocorticoid Receptor Antagonists
Spironolactone
Cardiovascular Agents
Diuretics
Diuretics, Potassium Sparing
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Natriuretic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014