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

March 7, 2022 updated by: ACS Biomarker

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 "

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

528

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Corbeil-Essonnes, France, 91106
        • Hôpital Sud Francilien
      • Nancy, France, 54500
        • CHU de Nancy
  • Germany
      • Berlin, Germany, D-13353
        • Charite Universitatsmedizin Berlin, Kardiologie
  • Ireland
      • Dublin, Ireland
        • St, Michaels Hospital
  • Italy
      • Cortona, Italy, 52044
        • Santa Margherita Hospital
  • Netherlands
      • Maastricht, Netherlands, 6202AZ
        • Maastricht University Medical Center
  • United Kingdom
      • Glasgow, United Kingdom, G51 4TF
        • Queen Elizabeth University Hospital
      • Hull, United Kingdom, HU16 5JQ
        • Castle Hill Hospital
      • Manchester, United Kingdom, M13 9WL
        • Central Manchester University Hospitals NHS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

60 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: OTHER
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: SINGLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Spironolacton Group
Spironolacton Sandoz given 25mg daily oral use
Drug: Spironolacton
Administration of Spironolacton 25 mg per day
Other Names:
  • Spironolacton Sandoz
NO_INTERVENTION: Control group
Only background treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in serum concentrations of PIIINP
Time Frame: 9 months
mmol/l
9 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
changes in serum plasma levels of Biomarkers
Time Frame: 9 months
PICP (synthesis), ICTP (degradation) and GAL3
9 months
Cardiac remodelling 1
Time Frame: 9 months
NT-proBNP (ELISA, central Lab), from baseline to 9 months (Certified centers and central readings).
9 months
Cardiac remodelling 2
Time Frame: 9 months
Left Ventricular Mass (g/m)
9 months
Cardiac remodelling 3
Time Frame: 9 months
Left Atrial Volume (ml)
9 months
Cardiorespiratory performance during exercise
Time Frame: baseline, 9 months
Shuttle walk test: Distance walked in meters
baseline, 9 months
Vascular function
Time Frame: screening, baseline, month1, month3, month 6, month 9
non-invasive technologies: BP lab Audicor system
screening, baseline, month1, month3, month 6, month 9
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.
9 months
Adverse events
Time Frame: screening, baseline, month1, month3, month 6, month 9
All adverse events
screening, baseline, month1, month3, month 6, month 9
Worsening renal function
Time Frame: screening, baseline, month1, month3, month 6, month 9
decline in eGFR >20%
screening, baseline, month1, month3, month 6, month 9
Hyperkalemia
Time Frame: screening, baseline, month1, month3, month 6, month 9
rise of serum potassium to >5.5 mmol/L
screening, baseline, month1, month3, month 6, month 9

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

ACS Biomarker

Collaborators

London School of Hygiene and Tropical Medicine
Institut National de la Santé Et de la Recherche Médicale, France

Investigators

  • Principal Investigator: John Cleland, PhD, Imperial College London

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2016

Primary Completion (ACTUAL)

September 30, 2018

Study Completion (ACTUAL)

January 31, 2019

Study Registration Dates

First Submitted

September 8, 2015

First Submitted That Met QC Criteria

September 21, 2015

First Posted (ESTIMATE)

September 22, 2015

Study Record Updates

Last Update Posted (ACTUAL)

March 8, 2022

Last Update Submitted That Met QC Criteria

March 7, 2022

Last Verified

March 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Homage

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Heart Failure

Clinical Trials on Spironolacton

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Hungary

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe