Tobramycin Nebulization to Prevent Multidrug-Resistant Ventilator-Associated Pneumonia

ConditionPneumonia, Ventilator-Associated

Trial statusNot yet recruiting

Trial phasePhase 4

Trial typeInterventional

Biological sexAll

Age18+

SponsorSecond Affiliated Hospital, Zhejiang University, School of Medicine

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age ≥18 years at enrollment.

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.

Written informed consent obtained from the patient or the patient's legally authorized representative.

Disqualifiers

Suspected or confirmed ventilator-associated pneumonia (VAP) on the day of enrollment, based on the attending physician's clinical judgment.

Continuous invasive mechanical ventilation for more than 96 hours before enrollment.

Planned extubation within the next 24 hours.

Previous tracheostomy.

Trial design

Design model

Parallel

Treatments tested in this trial

Tobramycin inhalation solution
Drug
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.
0.9% Sodium Chloride Placebo
Drug
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.

Treatment groups

574 Participants

are divided into 2 treatment groups

Group A: Nebulized TobramycinExperimental treatment 1 intervention

Group B: Nebulized 0.9% Sodium Chloride PlaceboPlacebo comparator 1 intervention

Trial outcomes

Primary outcomes

28-Day Cumulative Incidence of Multidrug-Resistant Ventilator-Associated Pneumonia

Percentage of randomized participants with a first episode of multidrug-resistant ventilator-associated pneumonia (MDR-VAP), adjudicated by an independent blinded endpoint adjudication committee. VAP develops after 48 hours of mechanical ventilation, including within 48 hours after weaning or extubation. Diagnosis requires new or progressive infiltrates, consolidation, or ground-glass opacities on chest X-ray or CT plus at least two of: temperature \>38°C, purulent airway secretions, and white blood cell count \>10 x 10\^9/L or \<4 x 10\^9/L. MDR-VAP additionally requires a positive quantitative lower respiratory tract culture (tracheal aspirate ≥10\^5 CFU/mL; bronchoalveolar lavage ≥10\^4 CFU/mL; protected specimen brush ≥10\^3 CFU/mL) with a causative bacterium resistant to at least three antimicrobial classes.

Time frame