Prevention of the Progression of Coronary Calcification With Use of Spironolactone in Peritoneal Dialysis Patients

Coronary Artery Calcification Clinical Trial

Official title:

Effect of Spironolactone on the Progression of Coronary Calcification in Peritoneal Dialysis Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03314493
• Other study ID #: U1111-1203-1767
• Status: Completed
• Phase: Phase 3
• First received: October 4, 2017
• Last updated: October 15, 2017
• Start date: November 7, 2014
• Est. completion date: November 10, 2016

Study information

• Verified date: October 2017
• Source: Professor Fernando Figueira Integral Medicine Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: November 10, 2016
• Est. primary completion date: November 10, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Calcinosis
• Coronary Artery Calcification
• Coronary Artery Disease
• Vascular Calcification

Intervention

Drug:
• Spironolactone 25Mg Tablet
Patients with coronary calcium score > 30 were treated with spironolactone for 12 months

Locations

Country	Name	City	State
Brazil	Instituto de Medicina Integral Prof. Fernando Figueira	Recife	Pernambuco

Sponsors (2)

Lead Sponsor	Collaborator
Professor Fernando Figueira Integral Medicine Institute	Federal University of São Paulo

Country where clinical trial is conducted

Brazil, 

References & Publications (5)

Fischer SS, Kempe DS, Leibrock CB, Rexhepaj R, Siraskar B, Boini KM, Ackermann TF, Föller 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. — View 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 F — View Citation

Nitta K, Akiba T, Nihei H. Aldosterone blockade and vascular calcification in hemodialysis patients. Am J Med. 2003 Aug 15;115(3):250. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Relative progression of the coronary calcium score	Percentage change in coronary calcium score from baseline to end of study. Coronary calcium score detected using multi-detector computed tomography and expressed in Agatston units.	12 months
Secondary	Absolute progression of the coronary calcium score	To evaluate the absolute progression of the coronary calcium score, defined as the difference between the final score and the baseline score. Coronary calcium score detected using multi-detector computed tomography and expressed in Agatston units.	12 months
Secondary	Adverse effects of spironolactone use	During follow-up, all patients were assessed monthly to evaluate the frequency of hyperpotassemia (serum potassium > 6mEq/L), hypotension (systolic blood pressure < 100 mmHg) and/or diastolic blood pressure < 60 mmHg) and gynecomastia defined as breast augmentation, painful or not.	12 months
Secondary	1 year change in laboratory parameters of mineral metabolism	Assess changes in serum levels of total calcium, phosphorus, alkaline phosphatase, 25(OH) vitamina D and intact parathyroid hormone, through periodic blood dosages of these parameters, during follow-up.	12 months
Secondary	Need for spironolactone dose reduction	In the presence of adverse effects, the dose of spironolactone was reduced from 25 to 12,5 mg per day.	12 months
Secondary	Causes of discontinuation of the study	Severe hyperpotassemia defined as serum potassium>7mEq/L; lack of improvement in the adverse effects of spironolactone with a dose reduction of 12,5 mg/day, ie, persistence of breasts enlargement, hypotension and hyperpotassemia (serum potassium < 6mEq/L); discontinuation of peritoneal dialysis due to renal transplantation or the need for hemodialysis transfer; withdrawal of consent at any time; and death were considered as causes for discontinuation of the study. For the evaluation of this outcome, the patients were submitted to medical visit and biochemical measures monthly.	12 months
Secondary	1 year change in laboratory parameters related to inflammation.	Assess changes on serum levels of c-reactive protein, albumin and fetuin-A, through periodic blood dosages of these parameters, during follow-up.	12 months