This proposal represents an application by the Mayo Clinic to be a REGIONAL CLINICAL CENTER (RCC) and a site for a CLINICAL RESEARCH SKILLS DEVELOPMENT CORE (SDC) in the Heart Failure Clinical Research Network (HFCRN). Mayo was a RCC and SDC site in the first funding period of the HFCRN. The Mayo RCC investigators designed and as serve as the principal investigator (PI) on two HFCRN trials (RELAX and ROSE) and three ancillary studies. We lead enrollment across the nine HFCRN sites. Our proposed protocol is POSE (Post-hospitalization Optimization Strategies Evaluation);a randomized, double- blind, placebo-controlled trial of subcutaneous (SQ) administration of BNP added to standard therapy at hospital dismissal and continued for 30 days in patients admitted for acute heart failure syndrome (AHFS). Hypothesis: As compared to placebo, therapy with SQ BNP will be associated with greater clinical stability at 60 days post discharge as assessed by a composite HF stability score. The long-term goal of POSE is to provide the rationale for a future adequately powered phase III study to test the impact of this strategy on HF readmissions. POSE is a small proof-of-concept study which tests a innovative therapeutic strategy at a novel AHFS therapeutic window extending the time course of therapeutic interventions in AHFS into the vulnerable post-discharge period to promote further clinical stabilization. POSE targets the appropriate AHFS subgroup based on the pathophysiology of AHFS and the biological actions of the proposed therapeutic and uses a novel, highly quantitative composite endpoint reflecting clinical stability. Finally, we document the successes of the MAYO HFCRN CLINICAL RESEARCH SKILLS DEVELOPMENT CORE (SDC) in the first cycle of funding and outline our continued strategy to train academic HF physician scientists in our Mayo SDC application.

Public Health Relevance

This proposal represents an application by the existing MAYO REGIONAL CLINICAL CENTER and MAYO CLINICAL RESEARCH SKILLS DEVELOPMENT CORE to participate in the Heart Failure Clinical Research Network. Mayo's participation will advance the goal of the Network which is to improve the treatment of HF by testing, through randomized clinical trials, interventions aiding in the management of HF and its morbidity.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Cooperative Clinical Research--Cooperative Agreements (U10)
Project #
5U10HL110262-03
Application #
8588992
Study Section
Special Emphasis Panel (ZHL1-CSR-K (O2))
Program Officer
Shah, Monica R
Project Start
2012-01-01
Project End
2018-12-31
Budget Start
2014-01-01
Budget End
2014-12-31
Support Year
3
Fiscal Year
2014
Total Cost
$468,369
Indirect Cost
$171,369
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
006471700
City
Rochester
State
MN
Country
United States
Zip Code
55905
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Zakeri, Rosita; Borlaug, Barry A; McNulty, Steven E et al. (2014) Impact of atrial fibrillation on exercise capacity in heart failure with preserved ejection fraction: a RELAX trial ancillary study. Circ Heart Fail 7:123-30
Margulies, Kenneth B; Anstrom, Kevin J; Hernandez, Adrian F et al. (2014) GLP-1 agonist therapy for advanced heart failure with reduced ejection fraction: design and rationale for the functional impact of GLP-1 for heart failure treatment study. Circ Heart Fail 7:673-9
Lindman, Brian R; Dávila-Román, Victor G; Mann, Douglas L et al. (2014) Cardiovascular phenotype in HFpEF patients with or without diabetes: a RELAX trial ancillary study. J Am Coll Cardiol 64:541-9
Mohammed, Selma F; Hussain, Imad; AbouEzzeddine, Omar F et al. (2014) Right ventricular function in heart failure with preserved ejection fraction: a community-based study. Circulation 130:2310-20
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Bishu, Kalkidan; Redfield, Margaret M (2013) Acute heart failure with preserved ejection fraction: unique patient characteristics and targets for therapy. Curr Heart Fail Rep 10:190-7
Chen, Horng H; AbouEzzeddine, Omar F; Anstrom, Kevin J et al. (2013) Targeting the kidney in acute heart failure: can old drugs provide new benefit? Renal Optimization Strategies Evaluation in Acute Heart Failure (ROSE AHF) trial. Circ Heart Fail 6:1087-94