Use of NT-proBNP Testing to Guide Heart Failure Therapy in the Outpatient Setting. (PROTECT)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Hoffmann-La Roche
Information provided by (Responsible Party):
James L. Januzzi, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00351390
First received: July 10, 2006
Last updated: April 26, 2012
Last verified: April 2012
  Purpose

Levels of amino-terminal pro-brain natriuretic peptide (NT-proBNP) a hormone released from the heart in patients with heart failure (HF) are strongly prognostic of adverse events, such as hospitalization or death from HF. Therapies that are beneficial for HF (such as beta blockers or angiotensin converting enzyme inhibitors) tend to lower levels of NT-proBNP in parallel with improvements in outcomes of patients so treated. Importantly, Nt-proBNP levels may identify a patient at high risk for adverse outcome from their HF, even in periods of apparent stability.

It remains unclear, however, whether treating patients based on their NT-proBNP concentrations would be associated with better outcomes compared to standard HF therapy without measurement of NT-proBNP values.

The goal of the PROTECT study is to evaluate whether treatment of patients with advanced and recently destabilized HF would benefit from NT-proBNP guided HF treatment, compared to standard HF therapy without such 'hormone guided' treatment.


Condition Intervention Phase
Congestive Heart Failure
Other: Drug therapy for HF
Other: NT-proBNP guided HF therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Use of Pro-Brain Natriuretic Peptide Targeted Therapy to Tailor Medical Management of Patients With Congestive Heart Failure Followed in an Outpatient Setting: the ProBNP Outpatient Tailored CHF Therapy (PROTECT) Study

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Effect of Standard of Care therapy versus Standard of Care plus NT-proBNP targeted therapy on total cardiovascular events [ Time Frame: One year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Effect of Standard of Care therapy versus Standard of Care plus NT-proBNP targeted therapy on the reduction of outpatient decompensated HF. [ Time Frame: One year ] [ Designated as safety issue: Yes ]
  • Effect of Standard of Care therapy versus Standard of Care plus NT-proBNP targeted therapy on change in NT-proBNP levels, both the change in absolute value as well as in relative value, from baseline to end of study. [ Time Frame: One year ] [ Designated as safety issue: Yes ]
  • Effect of Standard of Care therapy versus Standard of Care plus NT-proBNP targeted therapy alone on echocardiographic parameters including LV systolic and diastolic function, RV systolic and diastolic function, RV systolic pressures, degree of valvular [ Time Frame: One year ] [ Designated as safety issue: Yes ]
  • Effect of Standard of Care therapy versus Standard of Care plus NT-proBNP targeted therapy on the reduction of all cause mortality. [ Time Frame: One year ] [ Designated as safety issue: Yes ]
  • Ability of cTnT and hsCRP, independently as well as together with NT-proBNP, to predict cardiovascular endpoints. [ Time Frame: One year ] [ Designated as safety issue: No ]
  • Effect of Standard of Care therapy versus Standard of Care plus NT-proBNP targeted therapy alone on patient quality of life. [ Time Frame: One year ] [ Designated as safety issue: Yes ]
  • Cost benefits of NT-proBNP guided HF therapy versus standard of care. [ Time Frame: One year ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 300
Study Start Date: September 2005
Estimated Study Completion Date: December 2017
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: SOC
Standard of care HF therapy without NT-proBNP guidance
Other: Drug therapy for HF
Titration of HF meds in an aggressive out patient manner
Active Comparator: NT-proBNP arm
NT-proBNP plus standard HF management
Other: NT-proBNP guided HF therapy
drug therapy titrated to achieve NT-proBNP <1000 pg/mL

Detailed Description:

300 patients with class II-IV heart failure (HF) due to systolic dysfunction (left ventricular ejection fraction <40%) and recent (within 6 months) destabilized HF will be randomized 1:1 to either 'standard of care' therapy for their HF versus 'standard of care plus NT-proBNP guided' care.

At randomization, patients at MGH will undergo a 2-dimensional echocardiogram for cardiac structure and function.

Patients randomized to the 'standard of care' arm of the study will receive aggressive therapy for their HF, including evidence-based addition/titration of therapeutic agents in the trial, such as carvedilol or metoprolol XL, angiotensin converting enzyme inhibitors or angiotensin receptor blockers, spironolactone inhibitors (for those in class III or IV), digoxin (when applicable), loop diuretics, as well as nitrates with or without hydralazine. Biventricular pacing with/without ICD capability will be performed at the discretion of the investigator. Any changes in therapy will be accompanied by a 2 week follow up for re-assessment and further titration of medications, based on clinical judgment.

At each interim visit, patients in the 'standard of care' arm will have a Minnesota Living with Heart Failure questionnaire taken. For all visits, including those triggered by med changes, laboratories will be checked including serum chemistries; a sample of blood for blinded NT-proBNP, troponin T, and high sensitivity CRP will be obtained for measurement after the trial is complete.

Patients randomized to the 'standard of care plus NT-proBNP guided' arm will receive the same aggressive medical care as above, but will also have an unblinded measurement of NT-proBNP provided to the study investigator within an hour of first patient contact. Therapeutic decision-making will be first based on clinical acumen/judgment, but if the NT-proBNP is elevated, per protocol, the investigator will adjust therapies accordingly, including escalation of existing therapies with known effects on NT-proBNP levels, as well as possible addition of similar therapies not yet in use (such as spironolactone).

Patients will be followed for events including destabilized HF (in or outpatient), cardiovascular events (including ischemic complications, ICD discharge, or development of non-fatal arrhythmia such as atrial fibrillation), or death.

At the end of one year, event rates will be assessed and the outcomes in the two arms will be compared. As well, echocardiography will be performed on subjects at one year and differences from baseline in both groups will be assessed.

  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age > 21 years of age
  • Left ventricular ejection fraction ≤ 40%
  • NYHA class II-IV heart failure
  • Hospital admission, Emergency Department visit, or outpatient diuretic escalation of therapy for destabilized HF at least once in the 6 months prior to enrollment

Exclusion Criteria:

  • Severe renal insufficiency defined as serum creatinine > 2.5 mg/dl
  • Inoperable aortic valvular heart disease
  • Life expectancy <1 year due to causes other than HF such as advanced cancer
  • Cardiac transplantation or revascularization indicated or expected within 6 months
  • Severe obstructive or restrictive pulmonary disease, defined as a forced expiratory volume in 1S <1 L when diagnosed as standard of care.
  • Subject unable or unwilling to provide written informed consent
  • Coronary revascularization (PCI or CABG) within the previous 3 months
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00351390

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02467
Sponsors and Collaborators
Massachusetts General Hospital
Hoffmann-La Roche
Investigators
Principal Investigator: James L. Januzzi, MD, FACC Massachusetts General Hospital
  More Information

No publications provided by Massachusetts General Hospital

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: James L. Januzzi, Dr., Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00351390     History of Changes
Other Study ID Numbers: 2004-P-001447/12
Study First Received: July 10, 2006
Last Updated: April 26, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:
congestive heart failure treatment
congestive heart failure, prognosis
NT-proBNP testing

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases
Natriuretic Peptide, Brain
Natriuretic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 14, 2014