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Bioprofiling Response to Mineralocorticoid Receptor Antagonists for the Prevention of Heart Failure (Homage)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02556450
Recruitment Status : Completed
First Posted : September 22, 2015
Last Update Posted : February 21, 2019
Sponsor:
Collaborators:
Institut National de la Santé Et de la Recherche Médicale, France
London School of Hygiene and Tropical Medicine
Information provided by (Responsible Party):
ACS Biomarker

Brief Summary:

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

Detailed Description:
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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 528 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Other
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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure

Arm Intervention/treatment
Experimental: Spironolacton Group
Spironolacton Sandoz given 25mg daily oral use
Drug: Spironolacton
Administration of Spironolacton 25 mg per day
Other Name: Spironolacton Sandoz

No Intervention: Control group
Only background treatment



Primary Outcome Measures :
  1. Changes in serum concentrations of PIIINP [ Time Frame: 9 months ]
    mmol/l


Secondary Outcome Measures :
  1. changes in serum plasma levels of Biomarkers [ Time Frame: 9 months ]
    PICP (synthesis), ICTP (degradation) and GAL3

  2. Cardiac remodelling 1 [ Time Frame: 9 months ]
    NT-proBNP (ELISA, central Lab), from baseline to 9 months (Certified centers and central readings).

  3. Cardiac remodelling 2 [ Time Frame: 9 months ]
    Left Ventricular Mass (g/m)

  4. Cardiac remodelling 3 [ Time Frame: 9 months ]
    Left Atrial Volume (ml)

  5. Cardiorespiratory performance during exercise [ Time Frame: baseline, 9 months ]
    Shuttle walk test: Distance walked in meters

  6. Vascular function [ Time Frame: screening, baseline, month1, month3, month 6, month 9 ]
    non-invasive technologies: BP lab Audicor system

  7. 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.

  8. Adverse events [ Time Frame: screening, baseline, month1, month3, month 6, month 9 ]
    All adverse events

  9. Worsening renal function [ Time Frame: screening, baseline, month1, month3, month 6, month 9 ]
    decline in eGFR >20%

  10. Hyperkalemia [ Time Frame: screening, baseline, month1, month3, month 6, month 9 ]
    rise of serum potassium to >5.5 mmol/L



Information from the National Library of Medicine

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Ages Eligible for Study:   60 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent will be obtained prior to any study procedure;
  • Age >60 years
  • Clinical risk factors for developing heart failure, either:

    1. Coronary artery disease (h/o myocardial infarction, angioplasty or coronary artery bypass) Or
    2. At least two of the following:

      • Diabetes Mellitus requiring Hypoglycaemic Pharmacotherapy
      • Receiving pharmacological treatment for Hypertension
      • Microalbuminuria
      • Abnormal ECG (left ventricular hypertrophy, QRS >120msec, abnormal Q-waves)
  • Biological risk: NT-pro-BNP values between 125 and 1,000 ng/L or BNP values between 35 and 280 pg/ml (consistent with ESC guidelines indicating risk of HF but helping to rule out prevalent HF or atrial fibrillation which are associated with marked increases in NT-proBNP/BNP and should be investigated)

Exclusion Criteria:

  • Recent wound healing/inflammation:
  • Surgical procedure, coronary, cerebral or peripheral vascular events or infection in the prior 3 months
  • Cancer
  • Autoimmune disease
  • Hepatic Disease
  • Pre-existing diagnosis of clinical HF
  • Moderate/severe LV systolic ventricular dysfunction, i.e. LVEF <45%
  • Moderate or severe valve disease (investigators opinion)
  • eGFR< 30ml/min
  • Serum potassium >5.0 mmol/L
  • Treatment with an MRA or a loop diuretic (furosemide, bumetanide, ethacrynic acid or torasemide) in the previous three months
  • Potassium supplements or potassium-sparing diuretic at time of enrolment.
  • Atrial fibrillation within one month prior to inclusion (AF lasting <60 seconds on ambulatory ECG monitoring is permitted)

    •. History of hypersensitivity to spironolactone.

  • Requiring treatment with prohibited medication according to SmPC with exception of ACE inhibitors or angiotensin receptor blockers
  • Patients unable to give written informed consent.
  • Participation in another interventional trial in the preceding month
  • Ability to walk is, in the investigators opinion, clearly limited by joint disease or other locomotor problems rather than by cardiorespiratory fitness

Information from the National Library of Medicine

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


Locations
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France
Hopital Sud Francilien
Corbeil-Essonnes, France, 91106
CHU de Nancy
Nancy, France, 54500
Germany
Charite Universitatsmedizin Berlin, Kardiologie
Berlin, Germany, D-13353
Ireland
St, Michaels Hospital
Dublin, Ireland
Italy
Santa Margherita Hospital
Cortona, Italy, 52044
Netherlands
Maastricht University Medical Center
Maastricht, Netherlands, 6202AZ
United Kingdom
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
Sponsors and Collaborators
ACS Biomarker
Institut National de la Santé Et de la Recherche Médicale, France
London School of Hygiene and Tropical Medicine
Investigators
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Principal Investigator: John Cleland, PhD Imperial College London
  Study Documents (Full-Text)

Documents provided by ACS Biomarker:
Statistical Analysis Plan  [PDF] December 19, 2018

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: ACS Biomarker
ClinicalTrials.gov Identifier: NCT02556450    
Other Study ID Numbers: Homage
First Posted: September 22, 2015    Key Record Dates
Last Update Posted: February 21, 2019
Last Verified: February 2019
Additional relevant MeSH terms:
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Heart Failure
Heart Diseases
Cardiovascular Diseases