Prevention of the Progression of Coronary Calcification With Use of Spironolactone in Peritoneal Dialysis Patients
Primary Purpose
Coronary Artery Calcification, Vascular Calcification
Status
Completed
Phase
Phase 3
Locations
Brazil
Study Type
Interventional
Intervention
Spironolactone 25Mg Tablet
Sponsored by
About this trial
This is an interventional prevention trial for Coronary Artery Calcification focused on measuring Vascular calcification, Coronary calcification, Peritoneal Dialysis, Spironolactone
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
Sites / Locations
- Instituto de Medicina Integral Prof. Fernando Figueira
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
Spironolactone group
Control group
Arm Description
Spironolactone oral tablet 25mg/day, for 12 months
No spironolactone use
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
Full Information
NCT ID
NCT03314493
First Posted
October 4, 2017
Last Updated
October 15, 2017
Sponsor
Professor Fernando Figueira Integral Medicine Institute
Collaborators
Federal University of São Paulo
1. Study Identification
Unique Protocol Identification Number
NCT03314493
Brief Title
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
2. Study Status
Record Verification Date
October 2017
Overall Recruitment Status
Completed
Study Start Date
November 7, 2014 (Actual)
Primary Completion Date
November 10, 2016 (Actual)
Study Completion Date
November 10, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Professor Fernando Figueira Integral Medicine Institute
Collaborators
Federal University of São Paulo
4. Oversight
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronary Artery Calcification, Vascular Calcification
Keywords
Vascular calcification, Coronary calcification, Peritoneal Dialysis, Spironolactone
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
33 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Spironolactone group
Arm Type
Experimental
Arm Description
Spironolactone oral tablet 25mg/day, for 12 months
Arm Title
Control group
Arm Type
No Intervention
Arm Description
No spironolactone use
Intervention Type
Drug
Intervention Name(s)
Spironolactone 25Mg Tablet
Intervention Description
Patients with coronary calcium score > 30 were treated with spironolactone for 12 months
Primary Outcome Measure Information:
Title
Relative progression of the coronary calcium score
Description
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.
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Absolute progression of the coronary calcium score
Description
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.
Time Frame
12 months
Title
Adverse effects of spironolactone use
Description
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.
Time Frame
12 months
Title
1 year change in laboratory parameters of mineral metabolism
Description
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.
Time Frame
12 months
Title
Need for spironolactone dose reduction
Description
In the presence of adverse effects, the dose of spironolactone was reduced from 25 to 12,5 mg per day.
Time Frame
12 months
Title
Causes of discontinuation of the study
Description
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.
Time Frame
12 months
Title
1 year change in laboratory parameters related to inflammation.
Description
Assess changes on serum levels of c-reactive protein, albumin and fetuin-A, through periodic blood dosages of these parameters, during follow-up.
Time Frame
12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ana Paula S Gueiros, MD
Organizational Affiliation
Instituto de Medicina Integral Prof. Fernando Figueira
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Alex SR Souza, PhD
Organizational Affiliation
Instituto de Medicina Integral Prof. Fernando Figueira
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Aluizio B Carvalho, PhD
Organizational Affiliation
Universidade Federal de São Paulo
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
José E Gueiros, MD
Organizational Affiliation
Instituto de Medicina Integral Prof. Fernando Figueira
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Leuridan T Cavalcante, PhD
Organizational Affiliation
Instituto de Medicina Integral Prof. Fernando Figueira
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Dulce E Casarini, PhD
Organizational Affiliation
Universidade Federal de São Paulo
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Marina M Cadena
Organizational Affiliation
Instituto de Medicina Integral Prof. Fernando Figueira
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Karina T Nobrega, MD
Organizational Affiliation
Instituto de Medicina Integral Prof. Fernando Figueira
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Eveline B Calado, MD
Organizational Affiliation
Instituto de Medicina Integral Prof. Fernando Figueira
Official's Role
Study Chair
Facility Information:
Facility Name
Instituto de Medicina Integral Prof. Fernando Figueira
City
Recife
State/Province
Pernambuco
ZIP/Postal Code
50070-550
Country
Brazil
12. IPD Sharing Statement
Citations:
PubMed Identifier
20719979
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.
Results Reference
background
PubMed Identifier
23298834
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.
Results Reference
background
PubMed Identifier
26336165
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.
Results Reference
background
PubMed Identifier
12935835
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.
Results Reference
result
PubMed Identifier
24184249
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.
Results Reference
result
PubMed Identifier
33586138
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.
Results Reference
derived
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Prevention of the Progression of Coronary Calcification With Use of Spironolactone in Peritoneal Dialysis Patients
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