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

March 21, 2019 updated by: James L. Januzzi, Massachusetts General Hospital

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

152

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02467
        • Massachusetts General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 following guideline direction
Active Comparator: NT-proBNP arm
NT-proBNP plus standard HF management
Other: NT-proBNP guided HF therapy
Standard of care drug therapy following guideline direction, plus adjustment of medication titrated to achieve NT-proBNP <1000 pg/mL

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Effect of Standard of Care therapy versus Standard of Care plus NT-proBNP targeted therapy on total cardiovascular events
Time Frame: One year
One year

Secondary Outcome Measures

Outcome Measure
Time Frame
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
One year
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
One year
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
One year
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
One year
Ability of cTnT and hsCRP, independently as well as together with NT-proBNP, to predict cardiovascular endpoints.
Time Frame: One year
One year
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
One year
Cost benefits of NT-proBNP guided HF therapy versus standard of care.
Time Frame: One year
One year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Massachusetts General Hospital

Collaborators

Roche Diagnostics

Investigators

  • Principal Investigator: James L. Januzzi, MD, FACC, Massachusetts General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2005

Primary Completion (Actual)

June 1, 2009

Study Completion (Actual)

June 1, 2009

Study Registration Dates

First Submitted

July 10, 2006

First Submitted That Met QC Criteria

July 10, 2006

First Posted (Estimate)

July 12, 2006

Study Record Updates

Last Update Posted (Actual)

March 25, 2019

Last Update Submitted That Met QC Criteria

March 21, 2019

Last Verified

March 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2004-P-001447/12

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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