Clinical Outcomes of Inhaled Amikacin in Ventilator Associated Pneumonia (RCT)

Clinical Outcomes of Inhaled Amikacin in Ventilator Associated Pneumonia:A Group Randomized Controlled, Add on Trial

Article: Clinical Outcomes of Inhaled Amikacin in Ventilator-Associated Pneumonia: A group randomized controlled,add-on trial English:Patients in intensive care units often need ventilators to breathe. Sadly, these machines sometimes cause serious lung infections, known as ventilator-associated pneumonia (VAP). This study tested whether giving the antibiotic amikacin by inhalation (so itgoes straight into the lungs) could improve recovery when added to regular treatment. Researchers looked at how quickly infections cleared, how long patients needed the ventilator, and whether hospital stays were shortened. They also monitored for side effects.

Study Overview

• Status: Completed
• Conditions: Ventilator Associated Pneumonia ( VAP)
• Intervention / Treatment: Drug: Amikacin (Inhalation); Drug: Standard-of-Care Intravenous Antibiotics

Detailed Description

Ventilator-associated pneumonia continues to pose a significant therapeutic challenge due to rising antimicrobial resistance and suboptimal lung penetration of systemic antibiotics. Inhaled amikacin offers the advantage of delivering high local drug concentrations in the respiratory tract with minimal systemic toxicity.

This group randomized controlled add-on trial was conducted in the Surgical Intensive Care Units of Lahore General Hospital, Pakistan, from January to December 2024. A total of 180 adult patients diagnosed with VAP were allocated to one of two treatment arms:

Group N (Control): Empirical intravenous antibiotics (Meropenem ± Moxifloxacin)

Group A (Intervention): Inhaled amikacin (20 mg/kg/day in two divided doses) in addition to empirical intravenous antibiotics

Randomization was computer-generated and stratified by age, gender, and baseline SOFA score.

Clinical outcomes assessed included fever resolution, leukocyte normalization, reduced oxygen requirement, radiographic improvement, ventilator weaning, duration of mechanical ventilation, and length of ICU stay. Composite clinical improvement was defined as improvement in at least three out of five predefined domains.

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 4

Contacts and Locations

Study Locations

• Pakistan
  • Punjab Province
    • Lahore, Punjab Province, Pakistan, 54000
      • Lahore General Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Inclusion Criteria

Participants must meet all of the following:

1. Age 18-80 years
2. Currently receiving invasive mechanical ventilation

3. Clinical diagnosis of ventilator-associated pneumonia (VAP) based on:

   New or progressive infiltrate on chest imaging and at least two of the following:

   Fever > 38°C or hypothermia < 36°C

   Leukocytosis >12,000 or leukopenia <4,000 cells/µL

   Increased purulent respiratory secretions

   Worsening oxygenation indices

4. Initiation of systemic IV antibiotics for VAP
5. Availability of baseline respiratory sample for culture
6. Informed consent obtained from patient's legal guardian/attendantExclusion Criteria

Any of the following will lead to exclusion:

1. Known hypersensitivity to aminoglycosides (e.g., amikacin)
2. Chronic kidney disease Stage 4-5 or baseline serum creatinine >2 mg/dL
3. Pre-existing hearing loss or vestibular dysfunction
4. Severe bronchospasm or airway instability preventing safe nebulization
5. VAP due to confirmed pan-resistant microorganisms requiring alternative therapy

Exclusion Criteria:

-

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Inhaled Amikacin + Standard-of-Care Antibiotics; Participants will receive inhaled amikacin administered via nebulization in addition to standard intravenous antibiotic therapy for ventilator-associated pneumonia. Therapy continues for the prescribed antibiotic course and according to unit protocol.	Drug: Amikacin (Inhalation); Amikacin administered as an aerosolized solution via a vibrating mesh nebulizer once daily for the duration of systemic antibiotic therapy, according to ICU protocol for ventilator-associated pneumonia.; Drug: Standard-of-Care Intravenous Antibiotics; Intravenous antibiotics selected based on local antimicrobial guidelines and pathogen sensitivity for ventilator-associated pneumonia, administered for the full
Active Comparator: Participants will receive ONLY standard of care antibiotics; Participants will receive only standard intravenous antibiotic therapy for ventilator-associated pneumonia. Therapy continues for the prescribed antibiotic course and according to unit protocol.	Drug: Standard-of-Care Intravenous Antibiotics; Intravenous antibiotics selected based on local antimicrobial guidelines and pathogen sensitivity for ventilator-associated pneumonia, administered for the full

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of invasive mechanical ventilation	The total number of consecutive days a participant remains on invasive mechanical ventilation following enrollment. Extubation is considered successful if the participant remains off the ventilator for at least 48 hours without the need for reintubation.	From randomization until successful discontinuation of mechanical ventilation, assessed up to 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Improvement on Day 7	The proportion of participants achieving a predefined composite improvement in clinical status, including: Reduction in sputum volume and purulence Reduction in requirement for oxygen support Improvement in PaO₂/FiO₂ ratio Radiological improvement on chest imaging Resolution of fever (temperature <38°C for >24 hours) Measured using standardized clinical criteria for ventilator-associated pneumonia.	Day 7 after initiation of study treatment

Collaborators and Investigators

• Sponsor: Postgraduate Medical Institute, Lahore

Publications and helpful links

Helpful Links

• https://sites.google.com/view/inhaled-amikacin-vap-data

Study record dates

Study Major Dates

• Study Start (Actual): January 5, 2024
• Primary Completion (Actual): November 25, 2024
• Study Completion (Actual): September 30, 2025

Study Registration Dates

• First Submitted: December 8, 2025
• First Submitted That Met QC Criteria: January 17, 2026
• First Posted (Actual): January 27, 2026

Study Record Updates

• Last Update Posted (Actual): January 27, 2026
• Last Update Submitted That Met QC Criteria: January 17, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Adjunctive therapy; Mechanical ventilation; Ventilator associated pneumonia; Clinical improvement; Inhaled amikacin
• Additional Relevant MeSH Terms: Healthcare-Associated Pneumonia; Pathologic Processes; Disease Attributes; Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Lung Diseases; Pneumonia; Cross Infection; Iatrogenic Disease; Pathological Conditions, Signs and Symptoms; Pneumonia, Ventilator-Associated; Circulatory and Respiratory Physiological Phenomena; Carbohydrates; Glycosides; Aminoglycosides; Respiratory Mechanics; Respiration; Respiratory Physiological Phenomena; Kanamycin; Amikacin; Inhalation
• Other Study ID Numbers: LGH/PGMI/AMC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) underlying the results reported in this article may be shared upon reasonable request from qualified researchers.
• IPD Sharing Time Frame: Beginning 12 months after publication of study results, with no planned end date.
• IPD Sharing Access Criteria: Requests must include a methodologically sound proposal and will require approval by the Institutional Review Committee and execution of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; 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