Multi-center, randomized clinical trial to study the impact of in-hospital guidance for acutely decompensated heart failure treatment by predefined NT-proBNP targets (>30% reduction in NT-proBNP during admission) on the reduction of readmission rates and mortality

Guiding therapy of heart failure (HF) by an objective measure like NT-proBNP
has received intense attention. The gain that is made by this form of guidance
is modest when applied to chronic heart failure (CHF) patients. Recent post
discharge data from our own group does show that NT-proBNP guidance can detect
important short-term changes. Studies have also shown that NT-proBNP discharge
value and a >30% NT-proBNP reduction during admission are statistically
significant predictors of readmissions and mortality. These data suggest a role
for such NT-proBNP guidance, rather in an acute than in a chronic setting.
Acute admission for HF occurs frequent: in 2004, there were almost 25,000
hospital admissions in the Netherlands. Particularly worrisome is the high
percentage of readmissions which reaches 30 to 60% within 6 months, importantly
increasing the economic burden of this disease. In short, in-hospital care for
acutely decompensated heart failure may be improved by NT-proBNP guidance to
reduce the number of readmissions.

The primary objective of the present study is to demonstrate that NT-proBNP
guidance during in-hospital treatment for acutely decompensated heart failure
(to strive for >30% reduction) reduces readmissions and mortality and increases
the number of days alive out of hospital in the first 180 days compared to
therapy guided by standard clinical judgment. Morbidity and mortality is
measured in terms of days alive outside the hospital within the follow-up
period of 180 days. Endpoint events will be evaluated on an intention-to treat
basis.

Secondary objectives of the present study are:
1. To demonstrate within and between group effects of NT-proBNP titrated
therapy on secondary outcome measures such as final NT-proBNP levels.
2. To demonstrate NT-proBNP titrated heart failure therapy is cost-effective in
terms of hospitalization days in the first 180 days compared to conventional
clinically guided HF-therapy.
3. To demonstrate which of the proposed interventions to achieve >30% reduction
in NT-proBNP are relevant to reduce readmission and mortality in the first 180
days.
4. To demonstrate that NT-proBNP guidance during in-hospital treatment for
acutely decompensated heart failure (to strive for >30% reduction) reduces
readmissions and mortality in the first 90 days compared to therapy guided by
standard clinical judgment.
5. To assess whether primary and secondary outcome measures are exceedingly
prevalent in patients with elevated NT-proBNP levels that are not responsive to
pharmacological intervention.
6. To assess whether there is a significant difference in quality of life
between the groups treated with NT-proBNP titrated therapy or conventional
clinically-guided therapy.

Multi-center, randomized clinical intervention trial

Of patients who enter the study baseline NT-proBNP will be measured within 24
hours. Consenting patients are randomly assigned to one of the following
treatment strategies:
A. NT-proBNP guided treatment
B. Conventional clinically guided treatment

All patients will receive treatment for at least 3 days until they are
clinically stable. The randomization will take place during hospital admission
from day three or whenever the patient is clinically stable. Patients will be
included in a randomized controlled trial of NT-proBNP-titrated therapy (group
A) versus standard clinically guided therapy (group B).

In the NT-proBNP-titrated group A, NT-proBNP-levels will be reported to the
treating physician. The first NT-proBNP is measured within 24 hours after
admission. After the initial treatment and randomization, when the patient is
clinically stable, the NT-proBNP is measured again. Based on this NT-proBNP
measurement the discharge and follow-up of the patient is planned if the
patient meets both requirements: clinically stability and a NT-proBNP reduction
of >30%.

The NT-proBNP levels of patients in the clinically guided group B will be
measured but not revealed to patients, physicians or nurses. The first
NT-proBNP is measured within 24 hours after admission. After the initial
treatment and randomization, when the patient is clinically stable, the
NT-proBNP is measured (blind). If the patient is indeed clinically stable; the
physician should plan and organize the discharge and follow-up of the patient.

- The possible extend of admission with a maximum of three days.
- A follow up of 6 months with 4 visits of approximately 30 minutes with a
standard physical examination.