B-type Natriuretic Peptide for the Management of Weaning

Phase 3

Completed

• Conditions: Respiratory Insufficiency
• Interventions: Procedure: BNP-guided weaning; Procedure: Standard physician-directed weaning

• Registration Number: NCT00473148
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

Several clinical findings and clinical trials have suggested that the prognosis of intensive care unit (ICU) patients may be improved by minimizing the positive fluid balance. In particular, a global vascular overload could lead to weaning failure. The purpose of this international, multicenter, controlled, randomized trial is to test if the incorporation of a B-type natriuretic peptide (BNP) assay in a mechanical ventilation weaning protocol helps optimize the weaning process and reduce the duration of the ventilatory weaning period.

Detailed Description

Mechanical ventilation may give rise to complications with an incidence that increases with the duration of respiratory support. The purpose of the weaning procedure is to reduce the duration of mechanical ventilation without incurring a substantial risk of failure. Several clinical findings and clinical trials have suggested that the prognosis of ICU patients may be improved by minimizing the positive fluid balance. In particular, a global vascular overload could lead to weaning failure. B-type natriuretic peptide (BNP) is a hormone secreted by the ventricular cardiomyocytes in response to increased wall stretch, and its plasma levels are correlated with left ventricular filling pressure. In a preliminary study on 102 patients undergoing weaning from mechanical ventilation, the baseline BNP levels before weaning were found to be an independent risk factor for weaning failure. In surviving patients, BNP levels were significantly correlated with the duration of weaning procedure. The purpose of this international, multicenter, controlled, randomized trial is to test if the incorporation of a BNP assay in a mechanical ventilation weaning protocol helps optimize the weaning process and reduce the duration of ventilatory weaning period. Patients on mechanical ventilation presenting weaning criteria will be randomly assigned to two groups (standard physician-directed weaning or weaning guided by BNP assay). In order to standardize the weaning process, patients will be ventilated with an automatic computer-driven weaning system in the two groups (EVITA Smart Care System, Drager Medical). A blood sample will be collected from all patients every morning for BNP assay by the rapid immunofluorescence test (Triage BNP Test, BIOSITE). In the control group, the clinician will not be informed about the assay results and weaning will be carried out according to usual practices. Patients in the intervention group will receive diuretics according to a clinical practice algorithm based on plasma BNP levels and a fluid intake restriction. The primary endpoint for the two groups will be duration of weaning from mechanical ventilation.

Study Timeline

• Study First Submitted: 2007-05-11
• Study First Submitted QC: 2007-05-11
• Study First Posted: 2007-05-14
• Study Start: 2007-06
• Status Verified: 2008-11
• Primary Completion: 2010-03
• Study Completion: 2010-03
• Last Update Submitted: 2010-04-29
• Last Update Posted: 2010-04-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 265

Inclusion Criteria

• Intubated patient receiving mechanical ventilation for at least 24 hours
• SpO2 ≥ 90% with FiO2 ≤ 50% and PEP ≤ 8 cm H2O
• Hemodynamic stability without vasopressor therapy (dopamine ≤ 10 γ/kg/min and dobutamine ≤ 10 γ/kg/min are however allowed) nor fluid bolus (rapid infusion of at least 500 ml of macromolecules or 1000 ml of saline) during the twelve previous hours
• Sedation stopped or reduced during the previous 48 hours (analgesia may be continued)
• Stable neurological status with Ramsay score ≤ 5
• Body temperature > 36.0 °C and < 39 °C
• Informed consent signed by patient or close relative

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Exclusion Criteria

I: Definite exclusion criteria:

• Pregnancy or lactation
• Age < 18 years
• Known allergy to furosemide or sulphonamides
• Tracheotomy on inclusion
• Hepatic encephalopathy
• Cerebral edema, acute hydrocephaly
• Myasthenia gravis or acute idiopathic polyradiculoneuritis (Guillain-Barré syndrome)
• Decision to withdraw life support
• Prolonged cardiac arrest with poor neurological prognosis

II: Temporary exclusion criteria:

• Extubation of the patient programmed for the same day
• Acute right ventricular insufficiency (pulmonary embolism, right myocardial infarction)
• Renal insufficiency defined by one of the following: renal replacement therapy, or plasma urea > 25 mmol/L, or plasma creatinine > 180 µmol/L, or creatinine clearance < 30 mL/min or increase by more than 25% of plasma creatinine during the previous 24 hours
• One of the following metabolic abnormalities: blood sodium > 150 mEq/L; blood potassium < 3.5 mEq/L; metabolic alkalosis with arterial pH > 7.50
• Injection of iodinated contrast agent during the preceding six hours

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	BNP-guided weaning	BNP-guided treatment (Furosemide)
2	Standard physician-directed weaning	-

Primary Outcome Measures

Name	Time	Method
Duration of weaning from invasive ventilation	during ventilation

Secondary Outcome Measures

Name	Time	Method
Total duration of weaning from invasive and noninvasive ventilation	during hospitalisation
Total duration of mechanical ventilation	during hospitalisation
Length of stay in the ICU, length of stay in hospital, number of complications in intensive care, number of prolonged weanings (> 15 days), number of cases of nosocomial pneumonia, number of successful extubations, extubation complication rates	during hospitalisation in ICU
Cost of stay in the ICU	in the ICU
Cost of stay in hospital	during the all stay
Mortality in ICU	in ICU
Mortality sixty days after randomization	sixty days after randomization

Trial Locations

Locations (1)

CHU Henri Mondor; 🇫🇷 Creteil, France