Mechanical Insufflation-exsufflation and Hypertonic Saline in Nosocomial Bacterial Respiratory Tract Infection

Official title

Aspiration of Bronchial Secretions With Mechanical Insufflation-Exsufflation and Hypertonic Saline in Bacterial Nosocomial Tracheobronchitis and Pneumonia in Intubated Patients.

Overview

Multicenter, randomized open label clinical trial to evaluate IEM and HS as concomitant therapy for respiratory tract infection in patients under artificial ventilation in the ICU. Lung infection is a serious complication that may occur during hospital stay and may need artificial respiration or even develop during artificial ventilation for other causes. Current specific treatment consists of intravenous antibiotics. The current study evaluated whether aspiration and drainage of infected sputum helps curing this severe complication and whether nebulized HS has additional benefits, like loosening of secretions, eradicating bacteria or reducing inflammation.

Detailed description

Open label, randomized, multicenter (7 ICUs at 7 hospitals in Spain). The study has 2 main arms, pneumonia and tracheobronchitis.

If the diagnosis is pneumonia, subjects will be randomization to one of 3 study groups:

1. IV Antibiotic therapy 2. IV Antibiotic therapy + mechanical insufflation-Exsugglation (MI-E) 3. IV Antibiotic therapy + MI-E + nebulized hypertonic saline-hyaluronic acid (HS)

If the diagnosis is tracheobronchitis,subjects will be randomization to one of 3 study groups:

1. No specific therapy (recommendation of the Infectious Diseases Society of America) 2. IV Antibiotic therapy (common practice to prevent progressión to pneumona and shorten duration of intubation) 3. MI-E + HS

Safety will be compared by number of adverse events, severe adverse events and mortality between study groups in each main arm. Efficacy will be compared by duration of respiratory support and number of cases with worsening organ dysfunction.

Interventions

• Device Mechanical insufflation-exsufflation
  Combined use of mechanical insufflation-exsufflation with nebulized hypertonic saline in intubated patients with nosocomial respiratory tract infection
• Other Standard of Care
  systemic antibiotic therapy and catheter suctioning of secretions as recommended by guidelines
• Other Hypertonic saline with hyaluronic acid
  Commercially available combination of 7% hypertonic saline with 0.1% hyaluronic acid given as nebulization during the MI-E session

Primary outcome measures

• Median SOFA score increase >2 points on day 4 [Time frame: inclusion to day 4 after randomization]
• Median respiratory support-free days increase at day 28 [Time frame: Inclusion to day 28 after randomization]
• Percentage of subjects surviving/dying day 28 [Time frame: Inclusion to day 28 after randomization]

Secondary outcome measures (4)

• Subjects with bacterial eradication in respiratory samples at day 4 after randomization [Time frame: Day 3 to 5 after randomization]
• Subjects with bacterial eradication in respiratory samples at end of systemic antibiotic therapy [Time frame: 7 and 14 days after randomization]
• Median Length of ICU stay [Time frame: ICU admission to discharge or death in days]
• Median antibiotic-free days at 28 days [Time frame: from study inclusion to day 28]

Eligibility criteria

Inclusion criteria

• Signed informed consent
• Nosocomial pneumonia (vHAP or VAP) or nosocomial tracheobronchitis
• Intubated with a cuffed endotracheal tube or tracheostomy cannula.

Exclusion criteria

• Ominous prognosis
• Frank hemoptisis
• Barotrauma (pneumothorax or pneumomediastinum)
• Bronchospasm (patients on bronchodilators for previous bronchospasm may be included
• Unstable thoracic cage
• Suspected unmonitored intracraneal hypertension

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Spain · 8 centers

• Hospital Vall d´Hebrón. — Barcelona
• Hospital Nuestra Señora de la Candelaria. — Santa Cruz de Tenerife
• Hospital Clinico San Carlos — Madrid
• Hospital Clínico San Carlos — Madrid
• Hospital de la Princesa — Madrid
• Hospital Doce de Octubre — Madrid
• Hospital Álvaro Cunqueiro. — Vigo
• Virgen de la Salud — Toledo

Publications

• Ferreira de Camillis ML, Savi A, Goulart Rosa R, Figueiredo M, Wickert R, Borges LGA, Galant L, Teixeira C. Effects of Mechanical Insufflation-Exsufflation on Airway Mucus Clearance Among Mechanically Ventilated ICU Subjects. Respir Care. 2018 Dec;63(12):1471-1477. doi: 10.4187/respcare.06253. Epub 2018 Jul 17. PMID 30018175
• Knudtzen FC, Sprehn M, Vestbo J, Johansen IS. Mechanical insufflation/exsufflation compared with standard of care in patients with pneumonia: A randomised controlled trial. Eur J Anaesthesiol. 2020 Nov;37(11):1077-1080. doi: 10.1097/EJA.0000000000001209. No abstract available. PMID 33027229
• Sanchez-Garcia M, Santos P, Rodriguez-Trigo G, Martinez-Sagasti F, Farina-Gonzalez T, Del Pino-Ramirez A, Cardenal-Sanchez C, Busto-Gonzalez B, Requesens-Solera M, Nieto-Cabrera M, Romero-Romero F, Nunez-Reiz A. Preliminary experience on the safety and tolerability of mechanical "insufflation-exsufflation" in subjects with artificial airway. Intensive Care Med Exp. 2018 Apr 3;6(1):8. doi: 10.1186/ PMID 29616357
• Sanchez-Garcia M, Alvarez-Gonzalez M, Domingo-Marin S, Pino-Ramirez AD, Martinez-Sagasti F, Gonzalez-Arenas P, Cardenal-Sanchez C, Velasco-Lopez E, Nunez-Reiz A. Comparison of Mechanical Insufflation-Exsufflation and Hypertonic Saline and Hyaluronic Acid With Conventional Open Catheter Suctioning in Intubated Patients. Respir Care. 2024 Apr 22;69(5):575-585. doi: 10.4187/respcare.11566. PMID 38307525

Identifiers

NCT: NCT06310941 · ABSENTA · Pending

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗