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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Endotracheal Intubation; Nosocomial Pneumonia; Mechanical Ventilation Complication; Nosocomial Infection; Tracheobronchitis
• Intervention / Treatment: Other: Standard of Care; Device: Mechanical insufflation-exsufflation; Other: Hypertonic saline with hyaluronic acid

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.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Miguel Sánchez Garcia, MD. PhD.; Phone Number: +34658762739; Email: miguelsanchez.hcsc@gmail.com
• Study Contact Backup: Name: Belén De la Hera Hernanz, PhD; Phone Number: +34650624550; Email: belenhhernanz@gmail.com

Study Locations

• Spain
  • Barcelona, Spain
    • Hospital Vall d´Hebrón.
    • Contact: Xavier - Nuvials, MD, PhD
    • Contact: Ricard - Ferrer Roca, MD, PhD
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
    • Contact: Miguel Sanchez-Garcia, MD, PhD; Phone Number: +34658762739; Email: miguelsanchez.hcsc@gmail.com
    • Contact: Belén De la Hera Hernanz, PhD; Email: belenhhernanz@gmail.com
    • Contact: Fernando Martínez-Sagasti, MD, PhD
  • Madrid, Spain
    • Hospital Doce de Octubre
    • Contact: María Cruz - Martín-Delgado, MD
    • Contact: Mercedes Catalán, MD
  • Madrid, Spain
    • Hospital de La Princesa
    • Contact: Aris - Pérez Lucendo
    • Contact: Dolores - Rodríguez Huerta
  • Toledo, Spain
    • Virgen de la Salud
    • Contact: Gonzalo Hernández, MD, PhD
  • Las Palmas
    • Tenerife, Las Palmas, Spain
      • Hospital Nuestra Señora de la Candelaria.
      • Contact: Sergio - Rodríguez Ramos, MD
  • Pontevedra
    • Vigo, Pontevedra, Spain
      • Hospital Álvaro Cunqueiro.
      • Contact: Pilar Losada, MD, PhD
      • Contact: Dolores Vila, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard of Care; Standard of care: Systemic antibiotic therapy according to local protocol and at the discretion of the attending intensivist.	Other: Standard of Care; systemic antibiotic therapy and catheter suctioning of secretions as recommended by guidelines; Other Names: Routine care of respiratory tract infection
Experimental: Mechanical insufflation-exsufflation with hypertonic saline/hyaluronic acid comination; Systemic antibiotic therapy choice according to local protocol and at the discretion of the attending intensivist plus Mechanical insufflation-exsufflation (MI-E sessión tid during the first 48 hours, followed by MI-E if secretions are present or suspected; recommended settings +50 cmH2O/-50 cmH2O) with simultaneous nebulization of hypertonic saline (7%) with hyaluronic acid (0.1%).	Device: Mechanical insufflation-exsufflation; Combined use of mechanical insufflation-exsufflation with nebulized hypertonic saline in intubated patients with nosocomial respiratory tract infection; Other Names: Cough Assist; 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; Other Names: (Hyaneb-TM)
Experimental: Mechanical insufflation-exsufflation; Systemic antibiotic therapy choice according to local protocol and at the discretion of the attending intensivist plus Mechanical insufflation-exsufflation (MI-E sessión tid during the first 48 hours, followed by MI-E if secretions are present or suspected; recommended settings +50 cmH2O/-50 cmH2O)	Device: Mechanical insufflation-exsufflation; Combined use of mechanical insufflation-exsufflation with nebulized hypertonic saline in intubated patients with nosocomial respiratory tract infection; Other Names: Cough Assist

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median SOFA score increase >2 points on day 4	Increase in organ dysfunction score from baseline to day 4 after randomization.	inclusion to day 4 after randomization
Median respiratory support-free days increase at day 28	28 minus duration in days on high-flow nasal cannula + invasive ventilation.	Inclusion to day 28 after randomization
Percentage of subjects surviving/dying day 28	crude mortality on day 28 after randomization	Inclusion to day 28 after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subjects with bacterial eradication in respiratory samples at day 4 after randomization	Negative tests for causal microorganism in day 4 samples	Day 3 to 5 after randomization
Subjects with bacterial eradication in respiratory samples at end of systemic antibiotic therapy	Negative culture and molecular test for causative bacteria in samples at end of therapy	7 and 14 days after randomization
Median Length of ICU stay	Duration of ICU stay from admission to discharge or death	ICU admission to discharge or death in days
Median antibiotic-free days at 28 days	28 minus days without systemic antibiotic therapy	from study inclusion to day 28

Collaborators and Investigators

• Sponsor: Hospital San Carlos, Madrid
• Collaborators: FUNDACION PARA LA INVESTIGACION HOSPITAL CLINICO SAN CARLOS
• Investigators: Study Director: Belén De la Hera Hernanz, PhD, Hospial Clinico San Carlos

Publications and helpful links

General 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.
• 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/s40635-018-0173-6.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2026
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): December 30, 2027

Study Registration Dates

• First Submitted: February 27, 2024
• First Submitted That Met QC Criteria: March 12, 2024
• First Posted (Actual): March 15, 2024

Study Record Updates

• Last Update Posted (Estimated): March 26, 2025
• Last Update Submitted That Met QC Criteria: March 21, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: hypertonic saline; ventilator-associated pneumonia; mechanical insufflation-exsufflation; nebulization; tracheobronchitis; hospital-acquired pneumonia; cough assist device; nosocomial respiratory tract infection
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Respiratory Tract Diseases; Lung Diseases; Iatrogenic Disease; Healthcare-Associated Pneumonia; Pneumonia; Infections; Respiratory Tract Infections; Cross Infection; Immunologic Factors; Physiological Effects of Drugs; Protective Agents; Adjuvants, Immunologic; Viscosupplements; Hyaluronic Acid
• Other Study ID Numbers: ABSENTA; Pending (Clinical Research Information Service)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymyzed data sheet of all subjects and variables for a pre-specified analysis plan.
• IPD Sharing Time Frame: After study publication
• IPD Sharing Access Criteria: Anonymyzed data sheet of all subjects and variables for a pre-specified analysis plan.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No