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ALdosterone Antagonist Chronic HEModialysis Interventional Survival Trial (ALCHEMIST)

This study is currently recruiting participants.
See Contacts and Locations
Verified May 2017 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: May 4, 2017
Last verified: May 2017
  Purpose
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 Intervention Phase
End Stage Renal Failure on Dialysis Drug: Spironolactone Drug: Placebo Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Care Provider, 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 acute coronary syndrome or hospitalization for heart failure or nonfatal stroke or cardiovascular (CV) death [ Time Frame: 25 months ]

Secondary Outcome Measures:
  • The cumulate rate of non fatal MI or acute coronary syndrome, hospitalization for heart failure, nonfatal stroke or CV death [ Time Frame: 25 months ]
  • 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 ]
  • 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 ]

Estimated Enrollment: 825
Study Start Date: June 2013
Estimated Study Completion Date: June 2024
Estimated Primary Completion Date: June 2023 (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   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent
  • Health insurance beneficiary
  • Men and women, on hemodialysis for at least 45 days 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 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
  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 79 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

Responsible Party: University Hospital, Brest
ClinicalTrials.gov Identifier: NCT01848639     History of Changes
Other Study ID Numbers: ALCHEMIST
RB 12-079 ( Other Identifier: CHRU Brest )
Study First Received: May 3, 2013
Last Updated: May 4, 2017

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

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

ClinicalTrials.gov processed this record on July 27, 2017