ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on X

Kidney Week

Abstract: FR-OR113

ALdosterone Antagonist Chronic HEModialysis Interventional Survival Trial (ALCHEMIST): Primary Results

Session Information

Category: Dialysis

  • 801 Dialysis: Hemodialysis and Frequent Dialysis

Authors

  • Rossignol, Patrick, Université Lorraine, CHRU Nancy Inserm, Nancy, France
  • Zannad, Faiez, Université Lorraine, CHRU Nancy Inserm, Nancy, France
  • Massy, Ziad, Assistance Publique - Hopitaux de Paris, Boulogne Billancourt, Île-de-France, France
  • Azizi, Michel, Assistance Publique - Hopitaux de Paris, Paris, Île-de-France, France
  • Coadic, Julien, CHU de Brest, Brest, France
  • Tenailleau, Angélique, CHU de Brest, Brest, France
  • Mottier, Dominique, CHU de Brest, Brest, France
  • Guillemin, Francis, Université Lorraine, CHRU Nancy Inserm, Nancy, France
  • Chorfa, Fatima, Université Lyon 1, Villeurbanne, France; Hospices Civils de Lyon, Pôle Santé Publique, Service de Biostatistique et Bioinformatique, Lyon, France; CNRS, UMR 5558, Laboratoire de Biométrie et Biologie Évolutive, Équipe Biostatistique-Santé, Villeurbanne, France
  • Maucort-Boulch, Delphine, Université Lyon 1, Villeurbanne, France; Hospices Civils de Lyon, Pôle Santé Publique, Service de Biostatistique et Bioinformatique, Lyon, France; CNRS, UMR 5558, Laboratoire de Biométrie et Biologie Évolutive, Équipe Biostatistique-Santé, Villeurbanne, France
  • Frimat, Luc, Université de Lorraine, CHRU Nancy, Nancy, France
Background

There is currently no strong evidence-based pharmacological therapy to improve the excessively poor cardiovascular (CV) prognosis in chronic hemodialysis patients (HD). We aimed to investigate the effects of the steroidal mineralocorticoid receptor antagonist, spironolactone on CV outcomes in a high-risk HD population.

Methods

We conducted an international, multicenter, double-blind, randomized, placebo-controlled event-driven trial in HD patients with at least one CV comorbidity, abnormality or risk factor. Spironolactone 25 mg every other day was first administered open-label during a 4-week run-in period. Patients were excluded prior to randomization if serum potassium was greater than or equal to 5.5 mmol/l on two occasions during this run-in period or on the day of randomization. Randomized patients received spironolactone or placebo, both titrated up to 25 mg/day according to a pre-specified algorithm based on serum potassium monitoring. The primary outcome was the time to first MACE-expanded adjudicated event (cardiovascular death or non-fatal myocardial infarction (MI), acute coronary syndrome (ACS), stroke or hospitalization for heart failure (HHF)). The win ratio including 1. all-cause death 2. Time to a CV event (HHF, non-fatal MI, ACS or stroke) was tested in a hierarchical statistical strategy as secondary endpoint. We assumed that a total of 750 randomized patients followed for 2 years would provide 80% power to detect a risk reduction of the primary endpoint by 30% with a alpha risk of 5%. Assuming a 10% run-in withdrawal rate, 825 patients would have to be included in the run-in phase. Safety endpoints included incidence of severe hyperkalemia >6 mmol/L, as monitored at pre-specified visits, and as reported by investigators as serious adverse event. Clinicaltrials.gov NCT01848639

Results

First visit in first patient occurred on June 2013 and last visit in last patient occurred on November 2022. 823 patients were recruited. ALCHEMIST primary results will be presented at the ASN 2023 annual meeting.

Conclusion

ALCHEMIST was the first international double-blind randomized CV outcome trial of spironolactone vs placebo in high-risk HD.

Funding

  • Government Support - Non-U.S.