B-type Natriuretic Peptide (BNP)-Guided Diagnostic Strategy in Intensive Care Unit (ICU) Patients With Respiratory Failure

Does a Diagnostic Strategy Reduce Duration and Cost of Hospitalization in Patients With Acute Dyspnea? BASEL II Intensive Care Unit

Heart failure is a common reason for respiratory failure in ICU patients. The rapid and accurate differentiation of heart failure from other causes of respiratory failure remains a clinical challenge. BNP levels are significantly higher in patients with congestive heart failure as compared to patients with respiratory failure due to other causes. Therefore, rapid measurement of BNP might be very helpful in establishing or excluding the diagnosis of heart failure in patients with respiratory failure in the ICU.

The aim is to test the hypothesis that a BNP guided diagnostic strategy would improve the evaluation and management of patients presenting with primary (on admission) or secondary (while in the ICU) respiratory failure in the ICU and thereby reduce total treatment time and total cost of treatment.

Primary endpoints are time to discharge and total cost of treatment. Secondary endpoints are ICU length of stay, ICU cost, in-hospital mortality, 30-day mortality, cost-effectiveness, 6 and 12 month mortality, 6 and 12 month dyspnea score.

Study Overview

• Status: Completed
• Conditions: Respiratory Insufficiency
• Intervention / Treatment: Procedure: BNP guided diagnostics and initial therapy

Detailed Description

Background: Respiratory failure is not only the most important reason for admission of patients to a medical intensive care unit (ICU), but also a common reason for the deterioration of patients already treated in the ICU. It is a very serious condition associated with significant mortality. Heart failure is a common reason for respiratory failure in both circumstances. Unfortunately, the rapid and accurate differentiation of heart failure from other causes of respiratory failure in the ICU remains a clinical challenge. After evaluation of symptoms, physical examination, arterial blood gases, ECG, and chest x-ray, the clinician is often left with a considerable diagnostic uncertainty that results in misdiagnosis and delay in the initiation of appropriate therapy. In addition, misdiagnosis of heart failure causes morbidity, and increases total treatment time and treatment cost, because treatments for heart failure may be hazardous to patients with other conditions such as chronic obstructive pulmonary disease, and vice verse.

B-type natriuretic peptide (BNP) is a 32-amino acid polypeptide secreted from the cardiac ventricles in response to ventricular volume expansion and pressure overload. BNP levels are significantly higher in patients with congestive heart failure as compared to patients with respiratory failure due to other causes. Therefore, rapid measurement of BNP might be very helpful in establishing or excluding the diagnosis of heart failure in patients with respiratory failure in the ICU.

Aim: The aim is to test the hypothesis that a BNP guided diagnostic strategy would improve the evaluation and management of patients presenting with primary (on admission) or secondary (while in the ICU) respiratory failure in the ICU and thereby reduce total treatment time and total cost of treatment.

Endpoints: Primary endpoints: Time to discharge and total cost of treatment. Secondary endpoints: ICU length of stay, ICU cost, In-hospital mortality, 30-day mortality, cost-effectiveness, 6 and 12 month mortality, 6 and 12 month dyspnea score.

Patients and Methods: The trial is designed to enroll 286 patients presenting with primary (on admission) or secondary (while in the ICU) respiratory failure in the ICU. Patients will be randomly divided 1:1 into a clinical group using evaluation of patients according to local standards without the use of BNP (or other natriuretic peptides) and to a BNP group with early testing for BNP.

Expected results: The researchers hypothesize that a BNP guided diagnostic strategy will improve the evaluation and management of patients presenting with respiratory failure to the ICU and thereby reduce time to discharge and total cost of treatment.

Significance: If in fact, BNP testing could be shown to improve the evaluation and management of patients with respiratory failure in the ICU, this would represent a major advance in the clinical care of seriously ill patients, and as well, highlight the potential for considerable cost-saving. Accordingly, if this study would have a positive result and in fact demonstrate that a BNP guided diagnostic strategy reduces total treatment time and total cost of treatment, it would be the first randomized controlled trial demonstrating that a new diagnostic test improves the evaluation and management of ICU patients. Given the enormous expenses associated with intensive care, such a study seems overdue.

• Study Type: Interventional
• Enrollment (Actual): 286
• Phase: Phase 4

Contacts and Locations

Study Locations

• Switzerland
  • Luzern, Switzerland, 6000
    • Hospital of Luzern
  • Solothurn, Switzerland, 4500
    • Hospital of Solothurn
  • Basel-Stadt
    • Basel, Basel-Stadt, Switzerland, 4031
      • University Hospital Basel, Medical ICU
    • Basel, Basel-Stadt, Switzerland, 4031
      • University Hospital Basel, Surgical ICU
  • Bern
    • Interlaken, Bern, Switzerland, 3800
      • Hospital of Interlaken
    • Thun, Bern, Switzerland, 3600
      • Hospital of Thun

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients presenting with primary or secondary respiratory failure in the ICU

Exclusion Criteria:

• Age <18 years
• Obvious traumatic cause
• Renal dysfunction (serum creatinine >250umol/l)
• Sepsis
• Cardiopulmonary reanimation within the last 12 hours
• Shock
• Respiratory insufficiency triggered during bronchoscopy

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time to discharge	discharge
Total cost of treatment	until discharge

Secondary Outcome Measures

Outcome Measure	Time Frame
30-day mortality	30 days
ICU length of stay	discharge from ICU
ICU cost	until discharge from ICu
In-hospital mortality	discharge
cost-effectiveness	discharge
6 and 12 month mortality	12 months
6 and 12 month dyspnea score	12 months
Incidence/recognition of congestive heart failure (CHF) as a major cause of respiratory failure	discharge from ICU+
Incidence of diagnosed CHF as cause of respiratory failure in patients with COPD on ICU	discharge
Number of echo study performing during hospital stay	hospital discharge

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Collaborators: Swiss National Science Foundation
• Investigators: Principal Investigator: Christian Mueller, Prof, University Hospital, Basel, Switzerland

Publications and helpful links

General Publications

• Mueller C, Scholer A, Laule-Kilian K, Martina B, Schindler C, Buser P, Pfisterer M, Perruchoud AP. Use of B-type natriuretic peptide in the evaluation and management of acute dyspnea. N Engl J Med. 2004 Feb 12;350(7):647-54. doi: 10.1056/NEJMoa031681.
• Noveanu M, Breidthardt T, Reichlin T, Gayat E, Potocki M, Pargger H, Heise A, Meissner J, Twerenbold R, Muravitskaya N, Mebazaa A, Mueller C. Effect of oral beta-blocker on short and long-term mortality in patients with acute respiratory failure: results from the BASEL-II-ICU study. Crit Care. 2010;14(6):R198. doi: 10.1186/cc9317. Epub 2010 Nov 3.
• Noveanu M, Pargger H, Breidthardt T, Reichlin T, Schindler C, Heise A, Schoenenberger R, Manndorff P, Siegemund M, Mebazaa A, Marsch S, Mueller C. Use of B-type natriuretic peptide in the management of hypoxaemic respiratory failure. Eur J Heart Fail. 2011 Feb;13(2):154-62. doi: 10.1093/eurjhf/hfq188. Epub 2010 Oct 29.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: December 1, 2003
• Primary Completion (Actual): March 1, 2007
• Study Completion (Actual): March 1, 2008

Study Registration Dates

• First Submitted: August 12, 2005
• First Submitted That Met QC Criteria: August 12, 2005
• First Posted (Estimate): August 15, 2005

Study Record Updates

• Last Update Posted (Estimate): October 19, 2011
• Last Update Submitted That Met QC Criteria: October 18, 2011
• Last Verified: October 1, 2011

More Information

Terms related to this study

• Keywords: Respiratory failure; BNP
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Respiratory Insufficiency
• Other Study ID Numbers: BASEL II - ICU; PP00B-102853/1; 04.061; 36/01