Effectiveness of Routine Nebulization of Mucolytics and Bronchodilators During Mechanical Ventilation

NCT02159196 | Completed DMC

• 1 other identifier: Nebulae
• Study Type: interventional
• Target: 950
• Locations: 1 country
• Sites: 7

Brief Summary

The purpose of this multi-center randomized controlled non-inferiority trial is to determine the effect of a strategy using routine nebulisation of mucolytics and bronchodilators (four times daily) as compared to a strategy using nebulisation of mucolytics or bronchodilators only on clinical indication (i.e. occurrence of persistent thick and tenacious sputum or bronchospasm) in mechanically ventilated intensive care patients. The investigators will examine the effects in terms of ventilator-free days, defined as the number of days alive and free of ventilation at day 28 after start of ventilation. We hypothesize that a strategy that uses nebulisation of mucolytics or bronchodilators only on clinical indication not to be inferior to a strategy using preventive nebulisation of mucolytics or bronchodilators with regard to the number of ventilator free days in ICU patients at day 28.

Conditions

Respiratory Failure

Keywords

mechanical ventilation; nebulisation; respiratory failure

Outcome Measures

Primary Outcomes (1)

• Number of ventilator-free days at day 28

  The number of ventilator-free days (VFDs) is defined as the number of days from day 1 to day 28 after ICU admission and start of mechanical ventilation on which a patient breathes without assistance of the ventilator if the period of unassisted breathing lasted at least 24 consecutive hours. Patients who die or are mechanically ventilated longer than this period are assigned zero ventilator-free days.

  day 28 after ICU admission and intubation

Secondary Outcomes (4)

• Length of stay

  day 28 and day 90 after ICU admission and intubation

• Mortality

  day 28 and day 90 after ICU admission and intubation

• Pulmonary complications

  daily until detubation or day 28

• Side effects

  daily until detubation or day 28

Other Outcomes (1)

• Health care related costs

  until detubation or day 28

Study Arms (2)

acetylcysteine and salbutamol

ACTIVE COMPARATOR

Nebulisation of 3 mL-solution of acetylcysteine (fluimucil 100mg/ml, a mucolytic) and a 2.5 mL solution containing salbutamol (ventolin 2.5 Nebules 2.5mg/2.5 ml, a bronchodilator), administered every 6 hours (i.e., 4 times per day) within 24 hours after initiation of ventilation until tracheal extubation.

Drug: acetylcysteine and salbutamol

acetylcysteine or salbutamol

EXPERIMENTAL

Nebulisation on strict clinical indications; nebulisation of 3 mL-solution of acetylcysteine (fluimucil 100mg/ml, a mucolytic) in case of occurrence of persistent thick and tenacious sputum and only after active humidification is set. Nebulisation of 2.5 mL solution containing salbutamol (ventolin 2.5 Nebules 2.5mg/2.5 ml, a bronchodilator) in case of occurrence of bronchospasm.

Drug: acetylcysteine; Drug: salbutamol

Interventions

acetylcysteine and salbutamol DRUG

routine nebulisation of a 3 mL-solution of acetylcysteine (fluimucil 100mg/ml) and a 2.5 mL solution containing salbutamol (ventolin 2.5 Nebules 2.5mg/2.5 ml) four times daily

Also known as: 3 mL fluimucil 100mg/ml, 2.5 mL ventolin 2.5 Nebules 2.5mg/2.5 ml

acetylcysteine and salbutamol

acetylcysteine DRUG

nebulisation of acetylcysteine on strict clinical indications only', i.e. in case of occurrence of persistent thick and tenacious sputum

Also known as: 3 mL-solution of acetylcysteine (fluimucil 100mg/ml)

acetylcysteine or salbutamol

salbutamol DRUG

nebulisation of salbutamol on strict clinical indications only', i.e. in case of occurrence of bronchospasm

Also known as: 2.5 mL salbutamol (ventolin 2.5 Nebules 2.5mg/2.5 ml

acetylcysteine or salbutamol

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 year or older
• Expected duration of intubation and ventilation \> 24 hours
• Written informed consent

You may not qualify if:

• Age less than 18 years
• Ventilation before present ICU admission (though short-term ventilation in the emergency room or in the operation room for general anesthesia during surgery is allowed)
• Suspected or confirmed pregnancy
• Diagnosed with lung diseases for which inhalation therapy and/or oral steroids are used
• Diagnoses of: Guillain-Barré syndrome, complete spinal cord lesion or amyotrophic lateral sclerosis, Multiple Sclerosis, Myasthenia Gravis
• Known allergy for acetylcysteine or salbutamol

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead
• ZonMw: The Netherlands Organisation for Health Research and Development: collaborator

Study Sites (7)

Amphia Ziekenhuis Breda

Breda, North Brabant, 4818 CK, Netherlands

Location

Onze Lieve Vrouwe Gasthuis

Amsterdam, North Holland, 1090 HM, Netherlands

Location

Academic Medical Center

Amsterdam, North Holland, 1105 AZ, Netherlands

Location

Isala

Zwolle, Overijssel, 8025BT, Netherlands

Location

Sint Antonius Ziekenhuis

Nieuwegein, Utrecht, 3430 EM, Netherlands

Location

Rijnstate Ziekenhuis

Arnhem, 6815 AD, Netherlands

Location

MC Haaglanden

The Hague, 2512 VA, Netherlands

Location

Related Publications (4)

• van Meenen DMP, Algera AG, Schuijt MTU, Simonis FD, van der Hoeven SM, Neto AS, Abreu MG, Pelosi P, Paulus F, Schultz MJ; for the NEBULAE; PReVENT; RELAx investigators. Effect of mechanical power on mortality in invasively ventilated ICU patients without the acute respiratory distress syndrome: An analysis of three randomised clinical trials. Eur J Anaesthesiol. 2023 Jan 1;40(1):21-28. doi: 10.1097/EJA.0000000000001778. Epub 2022 Nov 18.

  PMID: 36398740 DERIVED

• van der Hoeven S, Ball L, Constantino F, van Meenen DM, Pelosi P, Beenen LF, Schultz MJ, Paulus F; NEBULAE-investigators. Effect of routine vs on-demand nebulization of acetylcysteine with salbutamol on accumulation of airway secretions in endotracheal tubes: substudy of a randomized clinical trial. Intensive Care Med Exp. 2020 Dec 18;8(Suppl 1):71. doi: 10.1186/s40635-020-00351-x.

  PMID: 33336283 DERIVED

• van Meenen DMP, van der Hoeven SM, Binnekade JM, de Borgie CAJM, Merkus MP, Bosch FH, Endeman H, Haringman JJ, van der Meer NJM, Moeniralam HS, Slabbekoorn M, Muller MCA, Stilma W, van Silfhout B, Neto AS, Ter Haar HFM, Van Vliet J, Wijnhoven JW, Horn J, Juffermans NP, Pelosi P, Gama de Abreu M, Schultz MJ, Paulus F. Effect of On-Demand vs Routine Nebulization of Acetylcysteine With Salbutamol on Ventilator-Free Days in Intensive Care Unit Patients Receiving Invasive Ventilation: A Randomized Clinical Trial. JAMA. 2018 Mar 13;319(10):993-1001. doi: 10.1001/jama.2018.0949.

  PMID: 29486489 DERIVED

• van der Hoeven SM, Binnekade JM, de Borgie CA, Bosch FH, Endeman H, Horn J, Juffermans NP, van der Meer NJ, Merkus MP, Moeniralam HS, van Silfhout B, Slabbekoorn M, Stilma W, Wijnhoven JW, Schultz MJ, Paulus F. Preventive nebulization of mucolytic agents and bronchodilating drugs in invasively ventilated intensive care unit patients (NEBULAE): study protocol for a randomized controlled trial. Trials. 2015 Sep 2;16:389. doi: 10.1186/s13063-015-0865-0.

  PMID: 26329352 DERIVED

MeSH Terms

Conditions

Respiratory Insufficiency

Interventions

Acetylcysteine; Albuterol

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins; Ethanolamines; Amino Alcohols; Alcohols; Amines; Phenethylamines; Ethylamines

Study Officials

• Marcus J Schultz, Prof Dr MD

  Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. Marcus J. Schultz

Study Record Dates

• First Submitted: June 6, 2014
• First Posted: June 9, 2014
• Study Start: July 1, 2014
• Primary Completion: March 1, 2017
• Study Completion: June 1, 2017
• Last Updated: June 16, 2017

Record last verified: 2017-06

Locations

NL (7)