Mucolytics in Patients on Invasive Mechanical Ventilation Due to Severe Acute Respiratory Syndrome Coronavirus 2

Mucolytic Agents and Ventilator-associated Pneumonia in Patients on Invasive Mechanical Ventilation Due to Severe Acute Respiratory Syndrome Coronavirus 2

It is planned to include patients over 18 years of age of both sexes, admitted to the Intensive Care Unit of Clinical Hospital Centre Split for respiratory insufficiency caused by severe acute respiratory syndrome coronavirus 2 in need of invasive mechanical ventilation.

The patients will be divided into four groups. Group 1 will receive N-acetylcysteine inhalation, Group 2 will receive inhalation with a 5% sodium chloride solution, and Group 3 will receive inhalation of 8.4% sodium bicarbonate, group 4 is a control group and will not routinely receive inhaled mucolytics preventively.

All inhalations will be given twice a day 12 hours apart. The first inhalation will be included within 12 hours of the patient being enrolled in the Intensive Care Unit. Patients will be randomized according to the type of inhalation they will receive, randomization will be done by all researchers through the random.org website, and the inhalation will be given by a nurse according to the agreed protocol.

RESEARCH GOALS

The aim of this study is to determine whether there is a difference in the frequency and duration of ventilator-associated pneumonia (VAP) and whether there is a difference in the number of days spent on mechanical ventilation and in mortality in these four groups of patients.

Hypothesis

Coronavirus disease 2019 patients on invasive mechanical ventilation and preventive sodium bicarbonate inhalation will have a lower incidence of ventilator-associated pneumonia and fewer days spent on invasive mechanical ventilation than patients inhaled with N-acetylcysteine, 5% saline, or patients without preventive inhalation.

Study Overview

• Status: Completed
• Conditions: Corona Virus Infection; Pneumonia, Ventilator-Associated
• Intervention / Treatment: Other: Inhalation of N-acetylcysteine; Other: Inhalation of 5% sodium chloride; Other: Inhalation of 8,4% sodium bicarbonate

• Study Type: Interventional
• Enrollment (Actual): 175
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Croatia
  • Split, Croatia, 21000
    • Clinical Hospital Centre Split

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients over 18 years of age with coronavirus pneumonia who need invasive mechanical ventilation.

Exclusion Criteria:

• Patients with polytrauma,
• pregnant women,
• severe hemodynamic instability,
• patients with pulmonary edema,
• less than 3 days spent in the ICU,
• patients who have microbiologically proven bacterial infection on arrival.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: N-acetylcysteine; Inhalation of 5 ml-s of N-acetylcysteine every 12 hours.	Other: Inhalation of N-acetylcysteine; Group 1 will receive N-acetylcysteine inhalation every 12 hours from the beginning of invasive mechanical ventilation.
Active Comparator: Hypertonic saline; Inhalation of 5 ml-s of 5% sodium chloride every 12 hours.	Other: Inhalation of 5% sodium chloride; Group 2 will receive inhalation with a 5% sodium chloride solution every 12 hours from the beginning of invasive mechanical ventilation.
Active Comparator: Bicarbonate; Inhalation of 5 ml-s 8.4% sodium bicarbonate every 12 hours.	Other: Inhalation of 8,4% sodium bicarbonate; Group 3 will receive inhalation of 8.4% sodium bicarbonate every 12 hours from the beginning of invasive mechanical ventilation.
No Intervention: Control group; No preventive inhalation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference between 4 arms regarding ventilator-associated pneumonia rate	Patients will be monitored for ventilator-associated pneumonia according to clinical criteria with a new or progressive pulmonary infiltrate on imaging plus supportive clinical findings of infection (eg, fever, secretions, leukocytosis). The diagnosis is confirmed when lower respiratory tract sampling identifies a pathogen.	Through study completion, an average of 6 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of ventilator-free days	Number of days from day 1 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.	Day 28 after ICU admission.
Mortality	Life status (alive or deceased) on day 28 after ICU admission.	Day 28 after ICU admission.

Collaborators and Investigators

• Sponsor: Clinical Hospital Center, Split

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2020
• Primary Completion (Actual): July 1, 2021
• Study Completion (Actual): July 29, 2021

Study Registration Dates

• First Submitted: February 6, 2021
• First Submitted That Met QC Criteria: February 13, 2021
• First Posted (Actual): February 16, 2021

Study Record Updates

• Last Update Posted (Actual): February 14, 2022
• Last Update Submitted That Met QC Criteria: February 11, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: hypertonic saline; N-acetylcysteine; coronavirus disease 2019; bicarbonate; Pneumonia, Ventilator-Associated
• Additional Relevant MeSH Terms: Pathologic Processes; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Disease Attributes; Cross Infection; Iatrogenic Disease; Healthcare-Associated Pneumonia; Severe Acute Respiratory Syndrome; Coronavirus Infections; Pneumonia; Pneumonia, Ventilator-Associated; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Protective Agents; Respiratory System Agents; Antioxidants; Antidotes; Free Radical Scavengers; Expectorants; Acetylcysteine; N-monoacetylcystine
• Other Study ID Numbers: 2181-147-01/06/M.S.-20-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

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