Clinical trial NCT00473148: B-type Natriuretic Peptide for the Management of Weaning
Official title: Weaning of Mechanical Ventilation Guided by the Natriuretic Peptide of Type B
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Respiratory Insufficiency
Keywords: Duration of weaning from invasive ventilation
Mechanical ventilation
Weaning
B-type natriuretic peptide
Fluid balance
Diuretics
Intubated patient receiving mechanical ventilation
for at least 24 hours
Respiratory insufficiency
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Dräger Médical S.A
name: Abbott RDx Cardiometabolic
First posted: 2007-05-14
Enrollment: 265
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

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

Primary outcomes:
measure: Duration of weaning from invasive ventilation
timeFrame: during ventilation
Secondary outcomes:
measure: Total duration of weaning from invasive and noninvasive ventilation
timeFrame: during hospitalisation
measure: Total duration of mechanical ventilation
timeFrame: during hospitalisation
measure: 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
timeFrame: during hospitalisation in ICU
measure: Cost of stay in the ICU
timeFrame: in the ICU
measure: Cost of stay in hospital
timeFrame: during the all stay
measure: Mortality in ICU
timeFrame: in ICU
measure: Mortality sixty days after randomization
timeFrame: sixty days after randomization
Other outcomes:
Locations:
city: Creteil
country: France
facility: CHU Henri Mondor
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Armand Mekonto Dessap, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dessap AM, Roche-Campo F, Launay JM, Charles-Nelson A, Katsahian S, Brun-Buisson C, Brochard L. Delirium and Circadian Rhythm of Melatonin During Weaning From Mechanical Ventilation: An Ancillary Study of a Weaning Trial. Chest. 2015 Nov;148(5):1231-1241. doi: 10.1378/chest.15-0525.
citation: Mekontso Dessap A, Katsahian S, Roche-Campo F, Varet H, Kouatchet A, Tomicic V, Beduneau G, Sonneville R, Jaber S, Darmon M, Castanares-Zapatero D, Brochard L, Brun-Buisson C. Ventilator-associated pneumonia during weaning from mechanical ventilation: role of fluid management. Chest. 2014 Jul;146(1):58-65. doi: 10.1378/chest.13-2564.
citation: Mekontso Dessap A, Roche-Campo F, Kouatchet A, Tomicic V, Beduneau G, Sonneville R, Cabello B, Jaber S, Azoulay E, Castanares-Zapatero D, Devaquet J, Lellouche F, Katsahian S, Brochard L. Natriuretic peptide-driven fluid management during ventilator weaning: a randomized controlled trial. Am J Respir Crit Care Med. 2012 Dec 15;186(12):1256-63. doi: 10.1164/rccm.201205-0939OC. Epub 2012 Sep 20.