Clinical Trial Result Information
Title of Study:
The 'Improved management of patients with congestive heart failure in Canada (IMPROVE-CHF CANADA)' Study.
Fast Facts:
| Protocol number: | CAN0010 |
| Sponsor: | Roche Diagnostics |
| Company division: | Diagnostic |
| Product name: | ELECSYS®proBNP |
| Phase of development: | NA |
| Therapeutic area, approved indication: | Congestive Heart Failure |
| Date of report: | 2/1/2008 |
Clinical study summary:
This randomized, double-blind study evaluated the use of plasma NT-proBNP measurements to improve the diagnostic accuracy of congestive heart failure and the predication of clinical outcomes in patients who present to emergency departments with acute dyspnea.
Study center(s) :
7 in Canada.
Objectives:
To accurately estimate the difference in sensitivity and specificity between NT-proBNP and conventional methods of CHF diagnosis; to establish the clinical utility of NT-proBNP as a tool to diagnose or exclude CHF for patients presenting with dyspnea to the urgent care facilities in a Canadian setting; to identify the costs and benefits and to provide the cost-effectiveness analysis associated with the use of NT-proBNP for assessing patients presenting with shortness of breath; to determine the prognostic value of NT-proBNP in patients who present to emergency rooms with dyspnea.
Methodology:
After enrollment, standard diagnostic tests were carried out, and a blood sample was taken for NT-proBNP measurement. At the end of the clinical evaluation, and with knowledge of the results of standard diagnostic tests except for NT-proBNP, the emergency room physician was asked to diagnose whether or not the patient has acute heart failure, and to estimate the likelihood that acute heart failure was the cause of dyspnea. Patients were randomized to one of 2 groups based on management strategies which involved either only conventional measures (the usual care group) or conventional measures plus knowledge of NT-proBNP results (the NT-proBNP group). The NT-proBNP results were made available to the physicians who managed the patients in the NT-proBNP group, immediately after randomization. As confirmation, two cardiologists provided with clinical data but not aware of the NT-proBNP results were asked to assign a diagnosis. Patients were classified by diagnosis at presentation into one of 3 categories: acute heart failure, not heart failure in a patient who had previous heart failure and/or left ventricular dysfunction, or no incident or prevalent heart failure.
Number of patients (planned/analyzed):
1200 planned; 500 enrolled; 483 analysed.
Diagnosis and main criteria for inclusion:
Adult patients presenting to the emergency departments of the participating sites with dyspnea of suspected cardiac etiology.
Criteria for evaluation (efficacy, safety):
Primary--duration of initial emergency room visit, and total direct medical costs of treatment. Secondary--initial length of stay in hospital, in-hospital and 60 day mortality, and re-hospitalization.
Statistical methods:
In the sample size calculation, the trial was designed to enrol at least 239 patients in each group, providing a power of 80% to detect a reduction in emergency department time from 9 to 7.2 hours (20% reduction) with the use of NT-proBNP-guided strategy.
Receiver-operating characteristic (ROC) curve analyses were performed for NT-proBNP with the adjudicated diagnosis as the reference standard. ROC curves for NT-proBNP and physician-estimated likelihood of heart failure were plotted. A logistic regression model which contained a combination of NT-proBNP and physician-estimated likelihood was analysed in predicting the final adjudicated diagnosis. A likelihood-ratio_2 test obtained from the logistic regression models was used to assess whether NT-proBNP added incremental value to clinical judgement in predicting heart failure. Comparisons of NT-proBNP values between the diagnostic categories were performed with the Kruskal-Wallis test.
All data were analysed according to the intention-to-treat principle.
Summary (efficacy, safety, other results):
A total of 246 patients were randomized to NT-proBNP-guided management, and 254 to usual care. Of these, 483 patients had 60-day outcome and economic data beyond the emergency department and the first hospitalization.
The final diagnoses adjudicated by 2 cardiologists blinded to the NT-proBNP results were acute heart failure in 230 patients (46%), not acute heart failure in patients with a history of heart failure and/or left ventricular dysfunction in 45 patients (9%) and not acute heart failure in patients without prior heart failure in 225 patients (45%). For all patients, the mean duration of stay in the emergency department was 7.2_5.4h (mean_SD). A total of 285 patients (57%) were subsequently admitted to hospital.
The findings of the study confirmed that the use of a NT-proBNP-guided strategy was superior to a sole conventional clinically guided strategy in the management of patients with suspected acute heart failure. As expected, NT-proBNP levels were higher in patients with an adjudicated diagnosis of heart failure compared with those without, and the addition of NT-proBNP testing to clinical judgement provided incremental value in helping to establish a diagnosis of heart failure, although NT-proBNP testing was not statistically superior to clinical judgement alone. Knowledge of NT-proBNP results reduced the time spent in the emergency department, the numbers of patients hospitalized, and the total direct medical costs over the 60-day follow-up.
Conclusions:
The results of the study showed that, in a universal access, publicly funded healthcare system, a strategy that uses NT-proBNP testing in conjunction with clinical assessment improves the overall management of patients presenting to the emergency department with suspected acute heart failure through the facilitation of diagnosis, and provides health cost savings accompanied by an improvement in selected clinical outcomes.
Click here for the protocol registry listing of this trial.
