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NCT07856355

PHASE4

Tobramycin Nebulization to Prevent Multidrug-Resistant Ventilator-Associated Pneumonia

Sponsor: Second Affiliated Hospital, Zhejiang University, School of Medicine

View on ClinicalTrials.gov

Summary

The TOP-MDRVAP trial will test whether inhaled tobramycin can safely prevent pneumonia caused by multidrug-resistant bacteria in adults who need a breathing machine. Tobramycin is an antibiotic. Multidrug-resistant bacteria are bacteria that resist treatment with several types of antibiotics. Pneumonia that develops in patients receiving breathing support through a breathing tube is called ventilator-associated pneumonia (VAP). This study will evaluate tobramycin as a preventive treatment, rather than as treatment for existing VAP. The study plans to enroll 574 adults aged 18 years or older in intensive care units (ICUs) at several hospitals. Participants must have received breathing support through a tube for 72 to 96 hours and be expected to need this support for at least another 72 hours. They must have at least one risk factor for infection with multidrug-resistant bacteria and must not have suspected or confirmed VAP when entering the study. Participants will be assigned by chance to one of two groups, with an equal chance of entering either group. One group will receive tobramycin inhalation solution, 300 mg in 5 mL, twice daily for 3 consecutive days. The other group will receive 5 mL of 0.9% saline, a saltwater solution containing no antibiotic, on the same schedule. A nebulizer will turn the solution into a fine mist delivered through the breathing tube. Both groups will receive standard measures to prevent VAP. Participants, their representatives, the healthcare professionals providing their direct care, and the researchers assessing outcomes will not know which study treatment each participant receives. The main question is whether fewer participants develop VAP caused by multidrug-resistant bacteria within 28 days after assignment to a study group. Researchers will also compare the occurrence of VAP from any cause, antibiotic use, time receiving breathing support, time spent in the ICU and hospital, and deaths within 28 and 90 days. Participants will be monitored for possible side effects, including kidney problems, narrowing of the airways, and complications involving the breathing tube or equipment. Samples will be tested for bacteria and antibiotic resistance. Follow-up will continue for up to 90 days after assignment, using hospital records or telephone contact to assess survival and recovery milestones, including discharge and the end of breathing support.

Official title: Tobramycin Nebulization to Prevent Multidrug-Resistant Ventilator-Associated Pneumonia: A Prospective, Multicenter, Double-Blind, Randomized Controlled Trial

Key Details

Gender

All

Age Range

18 Years - Any

Study Type

INTERVENTIONAL

Enrollment

574

Start Date

2026-10-07

Completion Date

2029-01-29

Last Updated

2026-10-02

Healthy Volunteers

Conditions

Pneumonia, Ventilator-Associated

Interventions

DRUG

Tobramycin inhalation solution

Tobramycin inhalation solution (300 mg/5 mL) is administered at a dose of 300 mg (5 mL) twice daily for 3 consecutive days, for a total of 6 planned doses. The ready-to-use solution is administered without additional dilution through the endotracheal tube using a vibrating mesh nebulizer connected to the ventilator circuit. Each nebulization continues until the nebulizer reservoir is empty. The intervention is administered to prevent multidrug-resistant ventilator-associated pneumonia (MDR-VAP), in addition to standard VAP prevention measures.

DRUG

0.9% Sodium Chloride Placebo

A 5 mL dose of 0.9% sodium chloride solution (normal saline) is administered as a placebo twice daily for 3 consecutive days, for a total of 6 planned doses. The solution is delivered through the endotracheal tube using the same type of vibrating mesh nebulizer, administration schedule, and nebulization procedure as the tobramycin intervention. Each nebulization continues until the nebulizer reservoir is empty. Participants also receive standard VAP prevention measures.

Inclusion Criteria: 1. Age ≥18 years at enrollment. 2. Invasive mechanical ventilation through an endotracheal tube for ≥72 hours and ≤96 hours, measured from the time of intubation, with an anticipated requirement for at least another 72 hours of invasive mechanical ventilation, as assessed by the attending physician. 3. At least one of the following risk factors for multidrug-resistant (MDR) bacterial infection: 3.1 Exposure to systemic antibiotics for ≥24 hours within the 30 days before enrollment. 3.2 Current hospitalization for at least 120 hours before randomization. 3.3 Septic shock requiring vasoactive medication to maintain a mean arterial pressure ≥65 mmHg, with a blood lactate level \>2 mmol/L. 3.4 Moderate-to-severe acute respiratory distress syndrome (ARDS), according to the Berlin definition, with a PaO2/FiO2 ratio ≤200 mmHg and positive end-expiratory pressure (PEEP) ≥5 cm H2O. 3.5 Current renal replacement therapy, including continuous renal replacement therapy or intermittent hemodialysis. 3.6 A history of MDR bacterial colonization or infection within the previous 12 months, documented by clinical culture. 4. Written informed consent obtained from the patient or the patient's legally authorized representative. Exclusion Criteria: 1. Suspected or confirmed ventilator-associated pneumonia (VAP) on the day of enrollment, based on the attending physician's clinical judgment. 2. Continuous invasive mechanical ventilation for more than 96 hours before enrollment. 3. Planned extubation within the next 24 hours. 4. Previous tracheostomy. 5. A history of allergy to tobramycin or any other aminoglycoside antibiotic. 6. Use of tobramycin within the 7 days before enrollment; ongoing treatment with any aminoglycoside antibiotic at enrollment; or a clinical indication for intravenous treatment with any aminoglycoside antibiotic at enrollment. 7. Chronic kidney disease (stages 4-5) with a baseline estimated glomerular filtration rate (eGFR) ≤30 mL/min/1.73 m², or acute kidney injury meeting the protocol-specified Kidney Disease: Improving Global Outcomes (KDIGO) stage 3 criteria: serum creatinine increased to three times baseline, serum creatinine \>353.6 μmol/L, urine output \<0.3 mL/kg/hour for more than 24 hours, or anuria for more than 12 hours. Patients currently receiving renal replacement therapy are exempt from this renal exclusion criterion. 8. Expected survival of no more than 48 hours, as assessed by the attending physician. 9. Pregnancy, indicated by a positive serum or urine human chorionic gonadotropin (hCG) test, or breastfeeding. 10. Concurrent participation in another interventional clinical study involving nebulized antibiotics or other ventilator-associated pneumonia prevention interventions.

Locations (1)

Second Affiliated Hospital of Zhejiang University School of Medicine

Hangzhou, Zhejiang, China