Bioprofiling Response to Mineralocorticoid Receptor Antagonists for the Prevention of Heart Failure (Homage)
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|ClinicalTrials.gov Identifier: NCT02556450|
Recruitment Status : Completed
First Posted : September 22, 2015
Last Update Posted : February 21, 2019
Despite advances in care, prognosis remains poor once overt Heart Failure (HF) has developed. Prevention is most efficient when directed toward patients at risk and when mechanistically targeted to patients most likely to respond. An increase in myocardial and possibly vascular collagen content (fibrosis) may be a major determinant of the transition to HF. In patients with hypertension and diabetes, two important risk-factors for HF, changes in blood markers of fibrosis occur before clinically overt HF develops. These markers are also related to prognosis.
In the general population, Galectin-3 (Gal-3), a potential marker of fibrosis, is associated with cardiovascular (CV) risk factors, and predicts development of HF. In animal models, Gal-3 is a key mediator of aldosterone-induced CV and renal fibrosis and dysfunction.
The investigators hypothesize that the mineralocorticoid receptor antagonist (MRA), spironolactone, may prevent HF by acting on extracellular matrix remodelling, especially in patients with active fibrogenesis, identified by high Gal-3 levels. The benefit/risk ratio of spironolactone might be superior in patients with a higher compared to lower plasma concentrations of Gal-3.
Main objective is to investigate whether spironolactone can favourably alter extra-cellular matrix remodelling, assessed by changes in the fibrosis biomarker Procollagen Type III N-Terminal Peptide (PIIINP), in patients at increased risk of developing heart failure and whether this effect is greater in patients with increased plasma concentrations of Gal-3.
|Condition or disease||Intervention/treatment||Phase|
|Heart Failure||Drug: Spironolacton||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||528 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Single (Outcomes Assessor)|
|Official Title:||Bioprofiling Response to Mineralocorticoid Receptor Antagonists for the Prevention of Heart Failure. A Proof of Concept Clinical Trial Within the EU FP 7 (European Union FP7) "HOMAGE" Programme " Heart OMics in AGing "|
|Study Start Date :||January 2016|
|Actual Primary Completion Date :||September 30, 2018|
|Actual Study Completion Date :||January 31, 2019|
Experimental: Spironolacton Group
Spironolacton Sandoz given 25mg daily oral use
Administration of Spironolacton 25 mg per day
Other Name: Spironolacton Sandoz
No Intervention: Control group
Only background treatment
- Changes in serum concentrations of PIIINP [ Time Frame: 9 months ]mmol/l
- changes in serum plasma levels of Biomarkers [ Time Frame: 9 months ]PICP (synthesis), ICTP (degradation) and GAL3
- Cardiac remodelling 1 [ Time Frame: 9 months ]NT-proBNP (ELISA, central Lab), from baseline to 9 months (Certified centers and central readings).
- Cardiac remodelling 2 [ Time Frame: 9 months ]Left Ventricular Mass (g/m)
- Cardiac remodelling 3 [ Time Frame: 9 months ]Left Atrial Volume (ml)
- Cardiorespiratory performance during exercise [ Time Frame: baseline, 9 months ]Shuttle walk test: Distance walked in meters
- Vascular function [ Time Frame: screening, baseline, month1, month3, month 6, month 9 ]non-invasive technologies: BP lab Audicor system
- heart failure or AF [ Time Frame: 9 months ]Rate of the clinical composite of development of heart failure or atrial fibrillation, non-fatal myocardial infarction or stroke or CV death from baseline to 9 months. The HOMAGE blinded clinical event committee will adjudicate all serious adverse events.
- Adverse events [ Time Frame: screening, baseline, month1, month3, month 6, month 9 ]All adverse events
- Worsening renal function [ Time Frame: screening, baseline, month1, month3, month 6, month 9 ]decline in eGFR >20%
- Hyperkalemia [ Time Frame: screening, baseline, month1, month3, month 6, month 9 ]rise of serum potassium to >5.5 mmol/L
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02556450
|Hopital Sud Francilien|
|Corbeil-Essonnes, France, 91106|
|CHU de Nancy|
|Nancy, France, 54500|
|Charite Universitatsmedizin Berlin, Kardiologie|
|Berlin, Germany, D-13353|
|St, Michaels Hospital|
|Santa Margherita Hospital|
|Cortona, Italy, 52044|
|Maastricht University Medical Center|
|Maastricht, Netherlands, 6202AZ|
|Queen Elizabeth University Hospital|
|Glasgow, United Kingdom, G51 4TF|
|Castle Hill Hospital|
|Hull, United Kingdom, HU16 5JQ|
|Central Manchester University Hospitals NHS|
|Manchester, United Kingdom, M13 9WL|
|Principal Investigator:||John Cleland, PhD||Imperial College London|