ALdosterone Antagonist Chronic HEModialysis Interventional Survival Trial (ALCHEMIST)

October 5, 2023 updated by: University Hospital, Brest

ALdosterone Antagonist Chronic HEModialysis Interventional Survival Trial (ALCHEMIST), Phase III b

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
823

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Bruxelles, Belgium, 1070
        • Hôpital Erasme- Bruxelles
  • France
      • Amiens, France, 80054
        • CHU Amiens
      • Avignon, France, 84000
        • Ch Avignon
      • Besançon, France, 25000
        • CHU Besançon
      • Boulogne Sur Mer, France, 62321
        • CH Boulogne sur Mer
      • Brest, France, 29609
        • CHRU Brest
      • Caen, France, 14033
        • CHU caen
      • Cahors, France, 46000
        • CH Cahors
      • Chambéry, France, 73000
        • CH Chambery
      • Cherbourg, France, 50100
        • CHPC Cherbourg
      • Colmar, France, 68000
        • AURAL Colmar
      • Colmar, France, 68024
        • Hôpitaux Civils de Colmar
      • Créteil, France, 94010
        • APHP Henri Mondor
      • Dijon, France, 21079
        • CHU Dijon Hôpital du Bocage
      • Grenoble, France, 38043
        • AGDUC Grenoble
      • Haguenau, France, 67500
        • AURAL Haguenau
      • Haguenau, France, 67500
        • CH Haguenau
      • La Roche Sur Yon, France, 85000
        • La Roche sur Yon
      • Lagny, France, 77400
        • Polyclinique de Lagny
      • Lille, France, 59000
        • Clinique Lille
      • Lille, France, 59037
        • Chu Lille
      • Limoges, France, 87000
        • ALURAD Limoges
      • Limoges, France, 87042
        • CHU Limoges
      • Lyon, France, 69003
        • CHU de Lyon
      • Lyon, France, 69004
        • AURAL La Croix Rousse
      • Lyon, France, 69007
        • Ch St Joseph-St Luc
      • Lyon, France, 69008
        • AURAL Lyon
      • Marseille, France, 13006
        • Clinique Bouchard
      • Marseille, France, 13009
        • Adpc Marseille
      • Marseille, France, 13385
        • APHM Marseille
      • Metz, France, 57000
        • Association de Metz
      • Metz, France, 58085
        • ALTIR Metz
      • Metz, France, 58085
        • CHR Metz-Thionville
      • Mulhouse, France, 68100
        • AURAL Mulhouse
      • Mulhouse, France, 68100
        • CH Mulhouse
      • Nancy, France, 54500
        • CHU Nancy
      • Nantes, France, 44093
        • CHU Nantes
      • Nice, France, 06002
        • CHU Nice
      • Nice, France, 06100
        • Clinique St Georges
      • Paris, France, 75013
        • AP-HP La Salpêtrière
      • Paris, France, 75014
        • AURA Paris 14ème
      • Paris, France, 75014
        • AURA Paris Plaisance
      • Paris, France, 75020
        • Hopital Tenon
      • Paris, France, 75743
        • AP-HP Necker
      • Paris, France
        • Institut Mutualiste Montsouris
      • Pierre-Bénite, France, 69495
        • CHU Lyon Sud
      • Reims, France, 51100
        • CHU de Reims
      • Reims, France, 51726
        • ARPDD Reims
      • Rennes, France, 35000
        • Chu Rennes
      • Reze, France, 44402
        • ECHO Confluent
      • Roscoff, France, 29260
        • Centre de Perharidy
      • Roubaix, France, 59056
        • CH Roubaix
      • Saint Denis, France, 97405
        • CHU de la Réunion Hôpital Félix Guyon
      • Saint Malo, France, 35400
        • Aub Saint Malo
      • Saint-Malo, France, 35403
        • CH Saint Malo
      • St Brieuc, France, 22000
        • CHG St Brieuc
      • Strasbourg, France, 67000
        • AURAL St Anne (AURAL Strasbourg)
      • Strasbourg, France, 67000
        • CHU Strasbourg
      • Strasbourg, France, 67000
        • Clinique Sainte Anne
      • Strasbourg, France, 67200
        • AURAL Strasbourg
      • Toulouse, France, 31059
        • CHU Toulouse
      • Tours, France, 37000
        • CHU Tours
      • Troyes, France, 10003
        • Ch Troyes
      • Valenciennes, France, 59322
        • Ch Valenciennes
      • Vandoeuvre les Nancy, France, 54504
        • ALTIR Nancy
      • Vantoux, France, 57070
        • Hôpitaux Privés de Metz- Hôpital Robert Schuman
      • Verdun, France, 55107
        • CH Verdun
      • Vichy, France, 03201
        • CH Vichy
    • Ardeche
      • Annonay, Ardeche, France, 07100
        • CH Ardeche Nord
  • Monaco
      • Monaco, Monaco
        • CH Princesse Grace

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
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
25 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Determine the effects of spironolactone compared to placebo on the composite winratio endpoint
Time Frame: 24 months

Following a hierarchical strategy of statistical tests including the primary endpoint.

Composite winratio endpoint of: all-cause mortality at 2 years according to the Finkelstein and Schoenfeld method.
24 months
Determine the effects of spironolactone compared to placebo on the composite winratio endpoint
Time Frame: 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.
24 months
non-cardiovascular mortality rate
Time Frame: 24 months
Additional secondary objectives will be considered in the context of hypothesis generation
24 months
cumulative accident rates forming the primary endpoint
Time Frame: 24 months
Additional secondary objectives will be considered in the context of hypothesis generation
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)
Time Frame: 24 months
Additional secondary objectives will be considered in the context of hypothesis generation
24 months
Incidence of procedures related to stenosis or vascular access thrombosis for hemodialysis (HD)
Time Frame: 24 months
Additional secondary objectives will be considered in the context of hypothesis generation
24 months
Incidence of coronary or peripheral revascularizations (including lower limb amputations)
Time Frame: 24 months
Additional secondary objectives will be considered in the context of hypothesis generation
24 months
The occurrence of atrial fibrillation
Time Frame: 24 months
Additional secondary objectives will be considered in the context of hypothesis generation
24 months
Incidence of hyperkalemia> 6 mmol/l
Time Frame: 24 months
Additional secondary objectives will be considered in the context of hypothesis generation
24 months
Blood pressure (systolic and diastolic pressure)
Time Frame: 24 months
Additional secondary objectives will be considered in the context of hypothesis generation
24 months
Blood pressure's variability inter visit (systolic and diastolic pressure)
Time Frame: 24 months
Additional secondary objectives will be considered in the context of hypothesis generation
24 months
Estimation of the effect of treatment on quality of life.
Time Frame: 24 months
KDQoL questionnaire ; minimum value = 0 ; maximum value = 100 ; higher score means a better outcome
24 months
Estimation of the effect of treatment on quality of life.
Time Frame: 24 months
Minnesota questionnaire ; minimum value = 0 ; maximum value = 100 ; higher score means a better outcome
24 months
Estimation of the effect of treatment on quality of life.
Time Frame: 24 months
SF36 questionnaire ; minimum value = 0 ; maximum value = 100 ; higher score means a better outcome
24 months

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Time Frame
Ancillary study:morbimortality data
Time Frame: 3, 5 and 10 years of follow-up after the double-blind study
3, 5 and 10 years of follow-up after the double-blind study
Ancillary study:establishment of a biological collection (serum bank and DNA biobank) for future biomarker studies
Time Frame: 24 months
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Hospital, Brest

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Institut National de la Santé Et de la Recherche Médicale, France
Central Hospital, Nancy, France

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 1, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 1, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 1, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 3, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 3, 2013

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 7, 2013

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 9, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 5, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ALCHEMIST
  • RB 12-079 (Other Identifier: CHRU Brest)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Statistical Analysis Plan

IPD Sharing Supporting Information Type

  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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Conditions

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