NCT02230891

Biomarker Guided Therapies in Stage A/B Heart Failure

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 58 (actual)
• Sponsor: VA Office of Research and Development · Federal
• Sex: All
• Age: 40 Years – 85 Years
• Healthy volunteers: Not accepted

Summary

Despite advances in cardiovascular care, the occurrence of heart failure (HF) is steadily increasing. The increase in HF rates poses enormous challenges, as once an individual becomes symptomatic or requires hospitalization with HF, the prognosis remains poor. Therefore, prevention of HF is essential. HF prevention is a critical issue as HF risk factors that include common medical conditions such as hypertension and diabetes are also increasing. However, not everyone with these risk factors develops HF. Using novel blood tests, the investigators propose to identify and treat subjects at higher HF risk to see if the investigators can stabilize or improve ultrasound measures known to be associated with HF risk. This study will enroll only Veterans.

Detailed description

Recently the investigators have shown that HF risk prediction can be improved using cardiac troponin T measured with a novel high-sensitivity assay (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Furthermore, hs-cTnT seems to identify individuals at higher risk among those with established risk factors (such as hypertension) for HF. In preliminary results, the investigators have shown that individuals with systolic blood pressure of 120-129 mm Hg and elevated hs-cTnT have a higher rate of incident HF than those with systolic blood pressure of 140-159 mm Hg and undetectable hs-cTnT. Therefore, the investigators believe that by using hs-cTnT to estimate HF risk the investigators can identify individuals in whom aggressive modification of risk factors such as high blood pressure will be associated with a favorable risk-benefit ratio. The investigators' objective/specific aim therefore is to evaluate if treatment of selected subjects with Stage A or B HF (i.e., those with hs-cTnT \>5 ng/L and an estimated 10-year HF hospitalization risk of \>5%) who have reasonably well-controlled blood pressure with antihypertensive agents (carvedilol or spironolactone) will be associated with improvement of surrogate markers associated with incident HF (i.e., speckle-tracked cardiac and vascular strain). Carvedilol and spironolactone were chosen for the following reasons: a) they are not routinely used as first-line antihypertensive agents; b) beta-blockade was associated with decreases in hs-cTnT in the preliminary analysis of subjects with established HF; and c) the mechanism of actions of carvedilol and spironolactone provide a sound scientific rationale for use in prevention of HF. Using a prospective open-label blinded end point (PROBE) design, the investigators propose to randomize 210 subjects aged \>40 years with systolic blood pressure between 120-155 mm Hg, cardiac troponin T (measured with a novel high-sensitivity assay) level \>5 ng/L, and 10-year HF risk \>5% (estimated using a validated laboratory model including demographic factors, NT-proBNP, and hs-cTnT) to receive carvedilol (nonselective beta-blocker), spironolactone (aldosterone antagonist), or usual care for 18 months. The primary end point will be change in global longitudinal systolic myocardial strain estimated using 2D speckle tracking. Additionally, changes in vascular strain and biomarkers will be evaluated. This study will help us identify whether both or either of the medications can be further tested in large randomized clinical trials to prevent the incidence of HF.

Conditions

• Hypertension
• Diabetes
• Cardiovascular Disease

Interventions

Type	Name	Description
DRUG	Carvedilol	Carvedilol is a non selective beta blocker
DRUG	Spironolactone	Spironolactone is an aldosterone antagonist and can lower blood pressure/ is used in heart failure
OTHER	Usual care	standard care as per primary care provider

Timeline

• Start date: 2014-10-01
• Primary completion: 2020-12-15
• Completion: 2020-12-15
• First posted: 2014-09-03
• Last updated: 2022-10-21
• Results posted: 2022-09-29

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study