The Second Follow-up Serial Infusions of Nesiritide (FUSION II) trial for advanced XXXX : study rationale and design.

@entity1 @entity712 @entity1011
BACKGROUND: @entity1 with persistently symptomatic advanced @entity712 have limited treatment options after appropriate use of standard evidence-based therapies. Current recommendations from the American College of Cardiology/American Heart Association guidelines for treatment of stage C/D @entity712 beyond standard therapy include ventricular replacement, investigational agents, and palliative interventions. Given the elevated risk of this @entity1 population, additional treatment options seem warranted. Natriuretic peptides are protean compounds that provoke vasodilation, natriuresis, neurohormonal antagonism, and reverse remodeling, but they have an uncertain risk-benefit profile affecting serum @entity1011 and clinical events. In the pilot, open-label FUSION I trial, the adjunctive administration of nesiritide with standard therapy for @entity1 with advanced @entity712 , was demonstrated to have a neutral effect on outcomes with no evidence of increased risk. Within a prespecified subset of high-risk @entity1 , a potential signal of benefit on a combined end point of mortality and cardiovascular hospitalization was identified. STUDY DESIGN: FUSION II is a 900- @entity1 randomized, placebo-controlled, double-blind, phase IIb trial designed to further assess the safety, efficacy, and optimal dosing frequency of outpatient nesiritide for advanced @entity712 . The primary end point is a composite of all-cause mortality and cardiorenal hospitalization. CONCLUSIONS: If a confirmatory signal of benefit is identified in FUSION II, a definitive phase III mortality/quality of life trial will be warranted. Additional issues related to the influence of disease management, the logistics of outpatient parenteral therapy administration, and future iterations of natriuretic peptide therapy will need to be investigated.
