Bronchoscopic Levofloxacin, Gentamicin, or Sham for Acute Exacerbation of Bronchiectasis

A Randomized Sham-Controlled Trial of Bronchoscopic Levofloxacin and Gentamicin Versus Sham in Mechanically Ventilated Bronchiectasis: Acute and 1-Year Outcomes

Randomized single-center trial evaluating whether bronchoscopic instillation of levofloxacin or gentamicin improves outcomes compared to a sham bronchoscopic procedure in adult ICU patients with non-cystic fibrosis bronchiectasis requiring invasive mechanical ventilation. The primary outcome is a ranked composite of in-hospital mortality and time to ventilator liberation. Safety and procedural adverse events are closely monitored.

Study Overview

• Status: Recruiting
• Conditions: Bronchiectasis With Acute Exacerbation
• Intervention / Treatment: Drug: Local instillation of gentamicin and Budesonide; Procedure: Bronchoscopic mechanical secretion suction and lavage; Drug: Local instillation of Levofloxacin and Budesonide; Procedure: Sham Bronchoscopy

Detailed Description

Bronchiectasis is a chronic suppurative and inflammatory lung disease of diverse etiology characterized by pathological and irreversible dilatation of the bronchial tree. The impairment of the mucociliary clearance, which results from chronic airway inflammation, may cause long-term colonization or recurrent infection of bacteria, especially Pseudomonas aeruginosa (PA), while bacterial colonization and recurrent infection can aggravate airway inflammation. Sputum retention caused by the impairment of mucociliary clearance can result in mucous plugs, which in turn contribute to airflow obstruction and dyspnea.

Clinically, the major manifestations of bronchiectasis include chronic cough with purulent sputum, dyspnea, and fatigue, which can significantly diminish patients' quality of life. The frequency of exacerbations and decline in lung function may lead to a poor prognosis and a decrease in quality of life.

The purpose of bronchiectasis management is to reduce exacerbations, prevent complications, and improve the quality of life. Long-term instillation of antibiotics and steroids can reduce the concentration of bacteria in the airways, decrease sputum production, attenuate lung function decline, and reduce acute pulmonary exacerbations without nephrotoxicity or ototoxicity. Dexamethasone is one of the most common glucocorticoids that can inhibit the expression levels of inflammatory factors in the airway and reduce the secretion of airway mucus. Topical administration could also reduce the systemic side effects.

• Study Type: Interventional
• Enrollment (Estimated): 315
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Ali A Ali, MSc; Phone Number: +2001064756136; Email: aliabuzaid@aun.edu.eg
• Study Contact Backup: Name: Ahmad M shaddad, MD; Phone Number: +2001111171930; Email: Shaddad_ahmad@aun.edu.eg

Study Locations

• Egypt
  • Assiut, Egypt, 71515
    • Recruiting
    • Assiut University Hospitals
    • Contact: Ali A Ali, MSc; Phone Number: 01064756136; Email: aliabuzaid@aun.edu.eg
    • Principal Investigator: Ahmad M Shaddad, MD
    • Principal Investigator: Aliae A Hussien, MD
    • Principal Investigator: Maiada K Hashem, MD
    • Principal Investigator: Ali A Ali, MSc

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• patients with bronchiectasis confirmed by high-resolution CT chest(HRCT)
• patients with acute exacerbation of bronchiectasis who need antibiotic treatment at the hospital due to exacerbation
• mechanically ventilated patients in the respiratory ICU
• Age more than or equal to 18 years

Exclusion Criteria:

• patients with active pulmonary tuberculosis
• patients with allergic bronchopulmonary aspergillosis
• patients who underwent interventional bronchoscopy for hemoptysis
• age less than 18 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Gentamicin group; This arm will undergo bronchoscopic airway clearance followed by local instillation of gentamicin (80 mg once) and Budesonide (0.5 mg) once.	Drug: Local instillation of gentamicin and Budesonide; Bronchoscopic local instillation of gentamicin and Budesonide; Other Names: Bronchoscopic instillation of gentamicin and steroids; Procedure: Bronchoscopic mechanical secretion suction and lavage; Bronchoscopic mechanical secretion suction and lavage
Experimental: Levofloxacin group; This arm will undergo bronchoscopic airway clearance followed by bronchoscopic instillation of levofloxacin 480 mg in isotonic saline during standardized bronchoscopy. And Budesonide (0.5 mg) once.	Procedure: Bronchoscopic mechanical secretion suction and lavage; Bronchoscopic mechanical secretion suction and lavage; Drug: Local instillation of Levofloxacin and Budesonide; Bronchoscopic local instillation of Levofloxacin and Budesonide; Other Names: Bronchoscopic instillation of levofloxacin and steroids
Sham Comparator: Sham group; Bronchoscopy for airway visualization only, no lavage or drug instillation (sham procedure).	Procedure: Sham Bronchoscopy; Bronchoscopy for airway visualization only, no lavage or drug instillation (sham procedure).; Other Names: Masking intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Days for weaning from mechanical ventilation	days of mechanical ventilation will be measured and compared between drug and conventional groups	one month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The amount of sputum production per day(ml/day)	The total amount of sputum per day will be measured and compared between the drug and conventional groups	one year
6-minute walking distance (meters)	The total recorded distance in 6 minutes in meters	one year
number of exacerbations (recorded number/year)	The number of reported exacerbations in one year	one year
Hospital admission	The number of reported hospital admissions in one year	one year
Quality of life assessment in bronchiectasis patients	The quality of life assessment in bronchiectasis patients using patient-reported outcome measures (Quality of Life Bronchiectasis questionnaire). It consists of 8 domains scored on a 0 - 100 scale (higher equals better QoL)	one year
Evaluation of anxiety in bronchiectasis patients using the Hamilton Anxiety rating Scale	The anxiety in bronchiectasis patients will be measured using the Hamilton Anxiety rating scale, which consists of 14 items ranging from 0 - 56 (higher equals more anxiety).	one year
Evaluation of depression in bronchiectasis patients using the Hamilton Depression Rating Scale	The depression in bronchiectasis patients will be measured using the Hamilton Depression rating scale, which consists of 17 items ranging from 0 - 52 (higher equals more depression).	one year

Collaborators and Investigators

• Sponsor: Assiut University
• Investigators: Principal Investigator: Ali A Ali, MSc, Assiut University; Study Chair: Aliae A Hussien, MD, Assiut University; Study Director: Ahmad M Shaddad, MD, Assiut University; Study Director: Maiada K Hashem, MD, Assiut University

Publications and helpful links

General Publications

• Chan SC, Shum DK, Tipoe GL, Mak JC, Leung ET, Ip MS. Upregulation of ICAM-1 expression in bronchial epithelial cells by airway secretions in bronchiectasis. Respir Med. 2008 Feb;102(2):287-98. doi: 10.1016/j.rmed.2007.08.013. Epub 2007 Oct 10.
• Murray MP, Govan JR, Doherty CJ, Simpson AJ, Wilkinson TS, Chalmers JD, Greening AP, Haslett C, Hill AT. A randomized controlled trial of nebulized gentamicin in non-cystic fibrosis bronchiectasis. Am J Respir Crit Care Med. 2011 Feb 15;183(4):491-9. doi: 10.1164/rccm.201005-0756OC. Epub 2010 Sep 24.
• King PT, Holdsworth SR, Freezer NJ, Villanueva E, Holmes PW. Characterisation of the onset and presenting clinical features of adult bronchiectasis. Respir Med. 2006 Dec;100(12):2183-9. doi: 10.1016/j.rmed.2006.03.012. Epub 2006 May 2.
• McShane PJ, Naureckas ET, Tino G, Strek ME. Non-cystic fibrosis bronchiectasis. Am J Respir Crit Care Med. 2013 Sep 15;188(6):647-56. doi: 10.1164/rccm.201303-0411CI.
• Flume PA, Chalmers JD, Olivier KN. Advances in bronchiectasis: endotyping, genetics, microbiome, and disease heterogeneity. Lancet. 2018 Sep 8;392(10150):880-890. doi: 10.1016/S0140-6736(18)31767-7.
• Polverino E, Goeminne PC, McDonnell MJ, Aliberti S, Marshall SE, Loebinger MR, Murris M, Canton R, Torres A, Dimakou K, De Soyza A, Hill AT, Haworth CS, Vendrell M, Ringshausen FC, Subotic D, Wilson R, Vilaro J, Stallberg B, Welte T, Rohde G, Blasi F, Elborn S, Almagro M, Timothy A, Ruddy T, Tonia T, Rigau D, Chalmers JD. European Respiratory Society guidelines for the management of adult bronchiectasis. Eur Respir J. 2017 Sep 9;50(3):1700629. doi: 10.1183/13993003.00629-2017. Print 2017 Sep.

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2023
• Primary Completion (Estimated): May 15, 2026
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: December 26, 2023
• First Submitted That Met QC Criteria: January 13, 2024
• First Posted (Actual): January 17, 2024

Study Record Updates

• Last Update Posted (Actual): July 17, 2025
• Last Update Submitted That Met QC Criteria: July 13, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Bronchoscopy; Levofloxacin; Bronchiectasis; Steroids; Gentamicins
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Bronchial Diseases; Bronchiectasis; Anti-Bacterial Agents; Anti-Infective Agents; Antineoplastic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Autonomic Agents; Peripheral Nervous System Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Enzyme Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Topoisomerase Inhibitors; Topoisomerase II Inhibitors; Respiratory System Agents; Anti-Asthmatic Agents; Bronchodilator Agents; Protein Synthesis Inhibitors; Cytochrome P-450 CYP1A2 Inhibitors; Anti-Infective Agents, Urinary; Budesonide; Levofloxacin; Gentamicins; Ofloxacin
• Other Study ID Numbers: AU-12578383

Plan for Individual participant data (IPD)

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

IPD Plan Description

All participant data will be recorded using a unique, study-specific Participant Identification (PID) number. This PID is not derived from any personal information and will be used for all data collection, analysis, and future data sharing. All datasets intended for sharing or publication will be thoroughly de-identified, with no direct or indirect personal identifiers included.

Results from this trial will be published in two main peer-reviewed manuscripts: one reporting outcomes from the acute hospitalization phase (primary analysis), and a second reporting on long-term, 1-year follow-up outcomes. Both publications will use only de-identified PID-linked data and will cite the same ClinicalTrials.gov registration number.

IPD Sharing Time Frame

Beginning 12 months after publication of the primary (acute phase) results, for a period of 3 years.

Data from both the acute hospital phase and the 1-year follow-up phase will be available after publication of the respective results in peer-reviewed journals.

IPD Sharing Access Criteria

De-identified individual participant data (IPD) will be made available to qualified researchers following publication of the primary and long-term results. Access will be granted for methodologically sound proposals that are consistent with the approved protocol and ethical standards. All requests must include a clear scientific rationale, analysis plan, and evidence of appropriate institutional review board (IRB) approval or waiver.

Data will be shared under a data use agreement, which ensures:

No attempt to re-identify participants, Use of data only for the approved research purpose, Compliance with all applicable privacy and security regulations. Requests will be reviewed by the trial's Steering Committee and Data Access Committee. Approved researchers will receive de-identified, PID-linked datasets and supporting documentation.

To request data access, interested parties should contact the Principal Investigator.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No