Singapore, Dec 23, 2009: Investigators at the Massachusetts General Hospital have announced that enrollment into the Pro-BNP Outpatient Tailored Congestive Heart Failure Therapy (PROTECT) study has been stopped early based on a positive interim analysis.

 

PROTECT, a prospective randomized trial comparing a strategy of aggressive heart failure therapy guided by levels of a cardiac hormone—amino-terminal pro-B type natriuretic peptide (NT-proBNP)—versus standard heart failure treatment without NT-proBNP guidance has been enrolling subjects in the Heart Center at the Massachusetts General Hospital since 2006.

 

Tests for NT-proBNP, a cardiac hormone that is released into the blood when the heart wall is stretched, are developed and marketed by Roche. NT-proBNP was approved by the US Food and Drug Administration (FDA) as an objective marker for the diagnosis and prognosis of heart failure as well as the risk assessment in patients with acute coronary syndrome.

 

The positive interim analysis suggests a strategy of NT-proBNP guided heart failure care was independently associated with a significant reduction in total cardiovascular events, the primary endpoint of the study, which included relevant cardiac outcomes, such as worsening heart failure, heart failure hospitalization, and cardiovascular death.

 

Commenting on the trial’s early suspension, lead investigator, Dr James Januzzi, Associate Professor of Medicine at Harvard Medical School and Director of the Cardiac Intensive Care Unit at the Massachusetts General Hospital said, “There are few reasons to stop a trial early, the most compelling of which is unequivocal success.  In the case of PROTECT, the data from interim analysis of the study appear to indicate a significant difference between the treatment arms in favor of the NT-proBNP group.”

 

“The decision to stop the trial indicates strong potential for the guided therapy approach. While previous studies have returned mixed results with respect to the approach of "guided therapy" with natriuretic peptide testing, the reduction in total cardiovascular events in the NT-proBNP arm suggests the important role of this cardiac hormone in the management of heart failure,” Januzzi said.

 

In the PROTECT study, patients with chronic systolic heart failure (left ventricular ejection fraction <40%) were randomized to one of two treatment approaches: a standard-of-care arm, where patients received aggressive guideline-compliant heart failure care, and an NT-proBNP arm, where patients were treated with similar aggressive clinical care, but investigators also aimed to decrease NT-proBNP concentrations to a level below 1,000 pg/mL, a value below which previous studies have shown the cardiovascular event risk in heart failure to be considerably lower.

 

Besides the primary endpoint of total cardiovascular events over a one year period, other endpoints in PROTECT will include effects of NT-proBNP guidance on quality of life, effect of NT-proBNP guided care on cardiac structure and function, and overall costs of care.

 

The trial is now closed. Final patient visits will be carried out and final data will be collected to allow a full analysis.  Final results of the study will be presented and published in 2010, once the analysis is complete.

 

“We are excited to see the full results of the trial, and ascertain next steps for proceeding forwards with the concept of biomarker guided heart failure care,” concluded Dr Januzzi.