Preventive nebulization of mucolytic agents and bronchodilating drugs in invasively ventilated intensive care unit patients (NEBULAE): study protocol for a randomized controlled trial.

Sophia M van der Hoeven, Jan M Binnekade, Corianne A J M de Borgie, Frank H Bosch, Henrik Endeman, Janneke Horn, Nicole P Juffermans, Nardo J M van der Meer, Maruschka P Merkus, Hazra S Moeniralam, Bart van Silfhout, Mathilde Slabbekoorn, Willemke Stilma, Jan Willem Wijnhoven, Marcus J Schultz, Frederique Paulus

Journal: Trials 2016;16():389

PMID: 26329352

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Abstract

BACKGROUND

Preventive nebulization of mucolytic agents and bronchodilating drugs is a strategy aimed at the prevention of sputum plugging, and therefore atelectasis and pneumonia, in intubated and ventilated intensive care unit (ICU) patients. The present trial aims to compare a strategy using the preventive nebulization of acetylcysteine and salbutamol with nebulization on indication in intubated and ventilated ICU patients.

METHODS/DESIGN

The preventive nebulization of mucolytic agents and bronchodilating drugs in invasively ventilated intensive care unit patients (NEBULAE) trial is a national multicenter open-label, two-armed, randomized controlled non-inferiority trial in the Netherlands. Nine hundred and fifty intubated and ventilated ICU patients with an anticipated duration of invasive ventilation of more than 24 hours will be randomly assigned to receive either a strategy consisting of preventive nebulization of acetylcysteine and salbutamol or a strategy consisting of nebulization of acetylcysteine and/or salbutamol on indication. The primary endpoint is the number of ventilator-free days and surviving on day 28. Secondary endpoints include ICU and hospital length of stay, ICU and hospital mortality, the occurrence of predefined pulmonary complications (acute respiratory distress syndrome, pneumonia, large atelectasis and pneumothorax), and the occurrence of predefined side effects of the intervention. Related healthcare costs will be estimated in a cost-benefit and budget-impact analysis.

DISCUSSION

The NEBULAE trial is the first randomized controlled trial powered to investigate whether preventive nebulization of acetylcysteine and salbutamol shortens the duration of ventilation in critically ill patients.

TRIAL REGISTRATION

NCT02159196, registered on 6 June 2014.

Address: Department of Intensive Care, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. [email protected].; Department of Intensive Care, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. [email protected].; Clinical Research Unit, Amsterdam, The Netherlands. [email protected].; Department of Intensive Care, Rijnstate, Arnhem, The Netherlands. [email protected].; Department of Intensive Care, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands. [email protected].; Department of Intensive Care, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. [email protected].; Laboratory of Experimental Intensive Care and Anesthesiology (L E I C A), Amsterdam, The Netherlands. [email protected].; Department of Intensive Care, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. [email protected].; Laboratory of Experimental Intensive Care and Anesthesiology (L E I C A), Amsterdam, The Netherlands. [email protected].; Department of Intensive Care, Amphia Hospital, Breda, Oosterhout and Etten-Leur, The Netherlands. [email protected].; Tias/Tilburg University, Tilburg, The Netherlands. [email protected].; Clinical Research Unit, Amsterdam, The Netherlands. [email protected].; Department of Intensive Care, Antonius Hospital, Nieuwegein, The Netherlands. [email protected].; Department of Intensive Care, Antonius Hospital, Nieuwegein, The Netherlands. [email protected].; Department of Intensive Care, Medical Center Haaglanden and Leidschendam, The Hague, The Netherlands. [email protected].; Department of Intensive Care, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands. [email protected].; Department of Intensive Care, Amphia Hospital, Breda, Oosterhout and Etten-Leur, The Netherlands. [email protected].; Department of Intensive Care, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. [email protected].; Laboratory of Experimental Intensive Care and Anesthesiology (L E I C A), Amsterdam, The Netherlands. [email protected].; Department of Intensive Care, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. [email protected].

DOI: 10.1186/s13063-015-0865-0

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MeSH Terms: Acetylcysteine, Administration, Inhalation, Albuterol, Bronchodilator Agents, Clinical Protocols, Cost-Benefit Analysis, Critical Illness, Drug Administration Schedule, Drug Costs, Drug Therapy, Combination, Expectorants, Hospital Mortality, Humans, Intensive Care Units, Length of Stay, Nebulizers and Vaporizers, Netherlands, Pneumonia, Ventilator-Associated, Pulmonary Atelectasis, Research Design, Respiration, Artificial, Time Factors, Treatment Outcome