A multicentre, double-blind, randomized controlled trial of inhaled amikacin versus placebo in critically ill patients with ventilator-associated tracheobronchitis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Regional Universitaire De Tours

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01], Diseases [C] - Respiratory Tract Diseases [C08]

Decision date (initial)

2026-01-12

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To assess whether a 5-day course of inhaled amikacin, compared to placebo, reduces the risk of progression to ventilator-associated pneumonia (VAP) at Day 28 in Intensive care unit (ICU) patients with ventilator-associated tracheobronchitis (VAT)

Secondary objectives 16

1. To assess whether a 5-day course of inhaled amikacin in ICU patients with VAT, compared to placebo prevents the transition from VAT to VAP at Day 7
2. To assess whether a 5-day course of inhaled amikacin in ICU patients with VAT, compared to placebo reduces the overall incidence of a first VAP episode (all pathogens) at Day 28
3. To assess whether a 5-day course of inhaled amikacin in ICU patients with VAT, compared to placebo reduces the overall incidence of a first VAP episode due to multidrug-resistant bacteria (MDRB) at Day 28
4. To assess whether a 5-day course of inhaled amikacin in ICU patients with VAT, compared to placebo accelerates the resolution of clinical signs of VAT
5. To assess whether a 5-day course of inhaled amikacin in ICU patients with VAT, compared to placebo induces a clearance of the pathogens responsible for VAT in tracheobronchial secretions at Day 7
6. To assess whether a 5-day course of inhaled amikacin in ICU patients with VAT, compared to placebo reduces mechanical ventilation (MV) duration
7. To assess whether a 5-day course of inhaled amikacin in ICU patients with VAT, compared to placebo increases the number of ventilator-free days at Day 28
8. To assess whether a 5-day course of inhaled amikacin in ICU patients with VAT, compared to placebo reduces exposure to systemic (i.e., intravenous and/or enteral administration) antibiotics at Day 28
9. To assess whether a 5-day course of inhaled amikacin in ICU patients with VAT, compared to placebo reduces the incidence of ICU-acquired intestinal colonization with MDRB at Day 28
10. To assess whether a 5-day course of inhaled amikacin in ICU patients with VAT, compared to placebo reduces the overall incidence of ICU-acquired infection due to MDRB at Day 28
11. To assess whether a 5-day course of inhaled amikacin in ICU patients with VAT, compared to placebo, reduces ICU and hospital length of stay (LOS)
12. To assess whether a 5-day course of inhaled amikacin in ICU patients with VAT, compared to placebo, reduces all-cause Day-28 and Day-90 mortality
13. To assess whether a 5-day course of inhaled amikacin in ICU patients with VAT, compared to placebo, improves health-related quality of life (HR-QoL) at Day 90
14. To appraise the respiratory safety of inhaled amikacin
15. To appraise the renal safety (incidence of acute kidney injury (AKI) at Day 28) of inhaled amikacin
16. To describe the pharmacokinetics of inhaled amikacin (pre-planned subsample)

Conditions and MedDRA coding

Patients with ventilator-associated tracheobronchitis

Study design 4 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Age ≥ 18 years
2. First episode of VAT during the ICU stay
3. Coverage by the French health insurance system (Social Security)
4. Written informed consent obtained from the patient, or, if the patient is not able to give written consent, from his or her legally designated representative (trusted person designated by the patient, or failing that a family member) and, failing that due to the urgency of the situation, inclusion will be performed by the investigator within the therapeutic window
5. For woman of childbearing potential: a negative pregnancy test result at the time of inclusion and contraception using an acceptable birth control method (CTFG recommendation)

Exclusion criteria 13

1. Previous VAP due to the pathogens responsible for VAT during the same ICU stay
2. On-going VAP (currently being treated)
3. VAT due to pathogens with intrinsic naturally amikacin resistance
4. On-going therapy with amikacin IV
5. AKI stage 2 or 3 of the KDIGO classification and/or advanced chronic kidney failure (glomerular filtration rate <30 mL/min), except in patients under renal replacement therapy (RRT)
6. Grade B or C cirrhosis (Child-Pugh classification)
7. Scheduled extubation within 24h
8. Known allergy to aminoglycosides
9. Myasthenia gravis
10. Persons covered by articles L1121-5 to L1121-8 of the CSP (corresponding to all protected persons: pregnant women, parturients, nursing mothers, persons deprived of their liberty by judicial or administrative decision, minors, and persons subject to a legal protection measure: guardianship or trusteeship)
11. Moribund patient
12. End-of-life decision
13. Previous inclusion in the present study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Incidence of transition from VAT to VAP at Day 28

Secondary endpoints 16

1. Incidence of transition from VAT to VAP at Day 7
2. Overall incidence of a first VAP episode (all pathogens) at Day 28
3. Overall incidence of a first VAP episode due to MDRB at Day 28
4. Time to resolution of clinical signs of VAT
5. Persistence of the pathogens responsible for VAT on ETA at Day 7
6. Total duration of MV
7. Number of ventilator-free days at Day 28
8. Number of defined daily doses of systemic antibiotics (i.e., intravenous and/or enteral administration) at Day 28
9. Incidence of ICU-acquired intestinal colonization with MDRB at Day 28
10. Overall incidence of ICU-acquired infection due to MDRB at Day 28
11. ICU and hospital LOS
12. All-cause Day-28 and Day-90 mortality rates
13. HRQoL in survivors at Day 90
14. Occurrence of respiratory adverse events related to amikacin nebulization (safety analysis)
15. Incidence of AKI at Day 28 (safety analysis)
16. Pharmacokinetics of inhaled amikacin (pre-planned subsample).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Regional Universitaire De Tours

Sponsor organisation

Centre Hospitalier Regional Universitaire De Tours

Address

2 Boulevard Tonnelle

City

Tours Cedex 9

Postcode

37044

Country

France

Scientific contact point

Organisation

Centre Hospitalier Regional Universitaire De Tours

Contact name

BARBIER François

Public contact point

Organisation

Centre Hospitalier Regional Universitaire De Tours

Contact name

BARBIER François

Locations

1 EU/EEA country · 17 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 24 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications