Clinical trial NCT03314493: Prevention of the Progression of Coronary Calcification With Use of Spironolactone in Peritoneal Dialysis Patients
Official title: Effect of Spironolactone on the Progression of Coronary Calcification in Peritoneal Dialysis Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Coronary Artery Calcification
Vascular Calcification
Keywords: Vascular calcification
Coronary calcification
Peritoneal Dialysis
Spironolactone
Lead sponsor: Professor Fernando Figueira Integral Medicine Institute
Sponsor class: OTHER
Collaborators: name: Federal University of São Paulo
First posted: 2017-10-19
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Vascular calcification is a frequent complication in dialysis patients and is strongly associated with mortality. Its pathogenesis is complex and involves a series of markers that act on the vascular microenvironment. There is evidence that aldosterone is one of the biomarkers and may have a role in osteoinductive pathways.The aim of this study was to evaluate the effect of spironolactone, an inhibitor of mineralocorticoid receptor, in the progression of coronary calcification in patients undergoing peritoneal dialysis.


Eligibility criteria: Inclusion Criteria:

* Coronary calcium score \> 30 Agatston unit
* Peritoneal dialysis for at least 6 months

Exclusion Criteria:

* Use of spironolactone in the last 3 months
* Mean serum potassium \> 6 mEq/L in the last 3 months
* Cardiac revascularization surgeries
* Arrhythmias
* Pregnancy

Primary outcomes:
measure: Relative progression of the coronary calcium score
timeFrame: 12 months
Secondary outcomes:
measure: Absolute progression of the coronary calcium score
timeFrame: 12 months
measure: Adverse effects of spironolactone use
timeFrame: 12 months
measure: 1 year change in laboratory parameters of mineral metabolism
timeFrame: 12 months
measure: Need for spironolactone dose reduction
timeFrame: 12 months
measure: Causes of discontinuation of the study
timeFrame: 12 months
measure: 1 year change in laboratory parameters related to inflammation.
timeFrame: 12 months
Other outcomes:
Locations:
city: Recife
country: Brazil
facility: Instituto de Medicina Integral Prof. Fernando Figueira
state: Pernambuco
Study officials:
affiliation: Instituto de Medicina Integral Prof. Fernando Figueira
name: Ana Paula S Gueiros, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Instituto de Medicina Integral Prof. Fernando Figueira
name: Alex SR Souza, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Universidade Federal de São Paulo
name: Aluizio B Carvalho, PhD
role: STUDY_DIRECTOR
affiliation: Instituto de Medicina Integral Prof. Fernando Figueira
name: José E Gueiros, MD
role: STUDY_CHAIR
affiliation: Instituto de Medicina Integral Prof. Fernando Figueira
name: Leuridan T Cavalcante, PhD
role: STUDY_CHAIR
affiliation: Universidade Federal de São Paulo
name: Dulce E Casarini, PhD
role: STUDY_CHAIR
affiliation: Instituto de Medicina Integral Prof. Fernando Figueira
name: Marina M Cadena
role: STUDY_CHAIR
affiliation: Instituto de Medicina Integral Prof. Fernando Figueira
name: Karina T Nobrega, MD
role: STUDY_CHAIR
affiliation: Instituto de Medicina Integral Prof. Fernando Figueira
name: Eveline B Calado, MD
role: STUDY_CHAIR
References:
citation: Fischer SS, Kempe DS, Leibrock CB, Rexhepaj R, Siraskar B, Boini KM, Ackermann TF, Foller M, Hocher B, Rosenblatt KP, Kuro-O M, Lang F. Hyperaldosteronism in Klotho-deficient mice. Am J Physiol Renal Physiol. 2010 Nov;299(5):F1171-7. doi: 10.1152/ajprenal.00233.2010. Epub 2010 Aug 18.
citation: Voelkl J, Alesutan I, Leibrock CB, Quintanilla-Martinez L, Kuhn V, Feger M, Mia S, Ahmed MS, Rosenblatt KP, Kuro-O M, Lang F. Spironolactone ameliorates PIT1-dependent vascular osteoinduction in klotho-hypomorphic mice. J Clin Invest. 2013 Feb;123(2):812-22. doi: 10.1172/JCI64093. Epub 2013 Jan 9.
citation: Tatsumoto N, Yamada S, Tokumoto M, Eriguchi M, Noguchi H, Torisu K, Tsuruya K, Kitazono T. Spironolactone ameliorates arterial medial calcification in uremic rats: the role of mineralocorticoid receptor signaling in vascular calcification. Am J Physiol Renal Physiol. 2015 Dec 1;309(11):F967-79. doi: 10.1152/ajprenal.00669.2014. Epub 2015 Sep 2.
citation: Nitta K, Akiba T, Nihei H. Aldosterone blockade and vascular calcification in hemodialysis patients. Am J Med. 2003 Aug 15;115(3):250. doi: 10.1016/s0002-9343(03)00293-6. No abstract available.
citation: Matsumoto Y, Mori Y, Kageyama S, Arihara K, Sugiyama T, Ohmura H, Yakushigawa T, Sugiyama H, Shimada Y, Nojima Y, Shio N. Spironolactone reduces cardiovascular and cerebrovascular morbidity and mortality in hemodialysis patients. J Am Coll Cardiol. 2014 Feb 18;63(6):528-36. doi: 10.1016/j.jacc.2013.09.056. Epub 2013 Oct 30.
citation: Hasegawa T, Nishiwaki H, Ota E, Levack WM, Noma H. Aldosterone antagonists for people with chronic kidney disease requiring dialysis. Cochrane Database Syst Rev. 2021 Feb 15;2(2):CD013109. doi: 10.1002/14651858.CD013109.pub2.