[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100658640":3},{"organization":4,"outcomesModule":7,"designInfo":86,"detailedDescription":91,"studyPopulation":91,"armGroups":99,"interventions":112,"overallOfficials":91,"centralContacts":122,"locations":132,"responsibleParty":148,"collaborators":150,"id":199,"slug":200,"hasResults":201,"nctId":202,"briefTitle":203,"officialTitle":204,"acronym":205,"eligibilityCriteria":206,"healthyVolunteers":201,"sex":207,"minAge":208,"maxAge":91,"enrollmentInfo":209,"targetDuration":91,"studyType":212,"phases":213,"briefSummary":215,"conditions":216,"keywords":218,"overallStatus":227,"whyStopped":91,"lastUpdateSubmitDate":228,"lastUpdatePostDateStruct":229,"startDateStruct":232,"completionDateStruct":234,"leadSponsor":236,"locationsCount":237},{"fullName":5,"class":6},"Second Affiliated Hospital, Zhejiang University, School of Medicine","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":13,"otherOutcomes":65},[9],{"measure":10,"description":11,"timeFrame":12},"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\u002FL or \\\u003C4 x 10\\^9\u002FL. MDR-VAP additionally requires a positive quantitative lower respiratory tract culture (tracheal aspirate ≥10\\^5 CFU\u002FmL; bronchoalveolar lavage ≥10\\^4 CFU\u002FmL; protected specimen brush ≥10\\^3 CFU\u002FmL) with a causative bacterium resistant to at least three antimicrobial classes.","From randomization through Day 28.",[14,17,19,22,25,28,32,36,39,43,46,49,52,56,59,62],{"measure":15,"description":16,"timeFrame":12},"Incidence Density of Multidrug-Resistant Ventilator-Associated Pneumonia","Number of first episodes of multidrug-resistant ventilator-associated pneumonia per 1,000 invasive mechanical ventilation days accumulated during the assessment period.",{"measure":18,"description":18,"timeFrame":12},"28-Day Incidence of Ventilator-Associated Pneumonia From Any Cause",{"measure":20,"description":21,"timeFrame":12},"Systemic Antibiotic Use Expressed as Antibiotic-Days","Cumulative systemic antibiotic use during the assessment period, expressed as antibiotic-days.",{"measure":23,"description":24,"timeFrame":12},"Days of Exposure to Systemic Antibiotics","Number of days on which a participant receives at least one systemic antibiotic during the assessment period. Each day with systemic antibiotic exposure is counted once, regardless of the number of antibiotics administered.",{"measure":26,"description":27,"timeFrame":12},"Duration of Mechanical Ventilation","Total duration of invasive and noninvasive mechanical ventilation, measured in days, during the assessment period.",{"measure":29,"description":30,"timeFrame":31},"Intensive Care Unit Length of Stay","Duration of intensive care unit stay, measured in days from randomization to ICU discharge, with follow-up through Day 90.","From randomization to ICU discharge, assessed up to Day 90.",{"measure":33,"description":34,"timeFrame":35},"Hospital Length of Stay","Duration of hospital stay, measured in days from randomization to hospital discharge, with follow-up through Day 90.","From randomization to hospital discharge, assessed up to Day 90.",{"measure":37,"description":38,"timeFrame":12},"28-Day All-Cause Mortality","Percentage of participants who die from any cause within 28 days after randomization.",{"measure":40,"description":41,"timeFrame":42},"90-Day All-Cause Mortality","Percentage of participants who die from any cause within 90 days after randomization. Survival status is obtained from hospital records or telephone follow-up.","From randomization through Day 90.",{"measure":44,"description":45,"timeFrame":12},"Incidence of Ventilator-Associated Pneumonia Caused by Tobramycin-Susceptible Gram-Negative Bacteria","Percentage of participants who develop ventilator-associated pneumonia caused by gram-negative bacteria that are susceptible to tobramycin on in vitro antimicrobial susceptibility testing.",{"measure":47,"description":48,"timeFrame":12},"Incidence of Ventilator-Associated Events","Percentage of participants who develop a ventilator-associated event, assessed using the protocol-specified 2023 Centers for Disease Control and Prevention\u002FNational Healthcare Safety Network definitions. Assessments include ventilator-associated conditions, infection-related ventilator-associated complications, and possible ventilator-associated pneumonia.",{"measure":50,"description":51,"timeFrame":12},"Incidence of New-Onset Acute Kidney Injury","Percentage of participants without acute kidney injury at baseline who develop Kidney Disease: Improving Global Outcomes (KDIGO) stage 1 or higher acute kidney injury during the assessment period.",{"measure":53,"description":54,"timeFrame":55},"Daily Trajectory of the Clinical Pulmonary Infection Score","Daily Clinical Pulmonary Infection Score (CPIS) values and their longitudinal changes during the assessment period, calculated using available clinical data.","Assessed daily from randomization until extubation or Day 28, whichever occurs first.",{"measure":57,"description":58,"timeFrame":12},"Time to First Successful Spontaneous Breathing Trial","Time, measured in days, from randomization to the first successful spontaneous breathing trial (SBT) during the assessment period.",{"measure":60,"description":61,"timeFrame":12},"Detection Rate of Tobramycin-Resistant Bacteria","Rate of isolation of tobramycin-resistant bacteria from respiratory specimens or blood cultures during the assessment period.",{"measure":63,"description":64,"timeFrame":12},"Composite Incidence of Serious Nebulization-Related Adverse Effects","Percentage of participants experiencing at least one serious adverse effect related to nebulization, including increased expiratory filter resistance, bronchospasm, or endotracheal tube obstruction.",[66,70,73,76,79,83],{"measure":67,"description":68,"timeFrame":69},"Longitudinal Changes in Respiratory Microbiome Alpha Diversity","Longitudinal changes in respiratory microbiome alpha diversity, assessed by 16S ribosomal RNA amplicon sequencing in participants enrolled in the microbiome substudy.","Protocol-specified Days 1, 4, 7, and 14, with additional sampling at VAP onset.",{"measure":71,"description":72,"timeFrame":69},"Longitudinal Changes in Respiratory Microbiome Beta Diversity","Longitudinal changes in respiratory microbiome beta diversity, assessed by 16S ribosomal RNA amplicon sequencing in participants enrolled in the microbiome substudy.",{"measure":74,"description":75,"timeFrame":69},"Longitudinal Changes in Antibiotic Resistance Gene Abundance","Longitudinal changes in antibiotic resistance gene abundance in respiratory samples, assessed by metagenomic next-generation sequencing.",{"measure":77,"description":78,"timeFrame":69},"Longitudinal Changes in Antibiotic Resistance Gene Diversity","Longitudinal changes in antibiotic resistance gene diversity in respiratory samples, assessed by metagenomic next-generation sequencing.",{"measure":80,"description":81,"timeFrame":82},"Tobramycin Concentration-Time Profile in Epithelial Lining Fluid","Tobramycin concentrations in epithelial lining fluid over time in participants enrolled in the pharmacokinetic substudy.","During the 3-day study treatment period.",{"measure":84,"description":85,"timeFrame":82},"Plasma Tobramycin Concentration-Time Profile","Plasma tobramycin concentrations over time in participants enrolled in the pharmacokinetic substudy.",{"allocation":87,"interventionModel":88,"interventionModelDescription":89,"primaryPurpose":90,"observationalModel":91,"timePerspective":91,"maskingInfo":92},"RANDOMIZED","PARALLEL","Participants are randomized in a 1:1 ratio to one of two parallel groups: nebulized tobramycin or nebulized 0.9% saline placebo. Both study interventions are administered twice daily for 3 consecutive days.","PREVENTION",null,{"masking":93,"maskingDescription":91,"whoMasked":94},"QUADRUPLE",[95,96,97,98],"PARTICIPANT","CARE_PROVIDER","INVESTIGATOR","OUTCOMES_ASSESSOR",[100,106],{"label":101,"type":102,"description":103,"interventionNames":104},"Nebulized Tobramycin","EXPERIMENTAL","Participants receive tobramycin inhalation solution, 300 mg in 5 mL per dose, administered through the endotracheal tube using a vibrating mesh nebulizer twice daily for 3 consecutive days (6 planned doses). The intervention is administered to prevent multidrug-resistant ventilator-associated pneumonia (MDR-VAP). Participants also receive standard ventilator-associated pneumonia (VAP) prevention measures.",[105],"Drug: Tobramycin inhalation solution",{"label":107,"type":108,"description":109,"interventionNames":110},"Nebulized 0.9% Sodium Chloride Placebo","PLACEBO_COMPARATOR","Participants receive 5 mL of 0.9% sodium chloride solution (normal saline) as a placebo, administered through the endotracheal tube using a vibrating mesh nebulizer twice daily for 3 consecutive days (6 planned doses). Participants also receive standard ventilator-associated pneumonia (VAP) prevention measures.",[111],"Drug: 0.9% Sodium Chloride Placebo",[113,118],{"type":114,"name":115,"description":116,"armGroupLabels":117,"otherNames":91},"DRUG","Tobramycin inhalation solution","Tobramycin inhalation solution (300 mg\u002F5 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.",[101],{"type":114,"name":119,"description":120,"armGroupLabels":121,"otherNames":91},"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.",[107],[123,128],{"name":124,"role":125,"phone":126,"phoneExt":91,"email":127},"Gensheng Zhang","CONTACT","+86 18806812331","genshengzhang@zju.edu.cn",{"name":129,"role":125,"phone":130,"phoneExt":91,"email":131},"Kai Zhang","+86 15150686177","zhangkai1993@zju.edu.cn",[133],{"facility":134,"status":91,"city":135,"state":136,"zip":137,"country":138,"countryCode":139,"cosmosGeoPoint":140,"geoPoint":145,"contacts":146},"Second Affiliated Hospital of Zhejiang University School of Medicine","Hangzhou","Zhejiang","310000","China","CN",{"type":141,"coordinates":142},"Point",[143,144],120.16142,30.29365,{"lat":144,"lon":143},[147],{"name":124,"role":125,"phone":126,"phoneExt":91,"email":127},{"type":149,"investigatorFullName":91,"investigatorTitle":91,"investigatorAffiliation":91,"oldNameTitle":91,"oldOrganization":91},"SPONSOR",[151,153,155,157,159,161,163,165,167,169,172,174,176,178,180,182,184,186,188,190,192,194,196],{"name":152,"class":6},"First Affiliated Hospital of Zhejiang University",{"name":154,"class":6},"Sir Run Run Shaw Hospital",{"name":156,"class":6},"The Fourth Affiliated Hospital of Zhejiang University School of Medicine",{"name":158,"class":6},"Zhejiang Hospital",{"name":160,"class":6},"Zhejiang Provincial People's Hospital",{"name":162,"class":6},"Lishui Country People's Hospital",{"name":164,"class":6},"Jinhua People's Hospital",{"name":166,"class":6},"The First People's Hospital of Huzhou",{"name":168,"class":6},"Second Affiliated Hospital of Wenzhou Medical University",{"name":170,"class":171},"Ningbo Medical Center Lihuili Hospital","OTHER_GOV",{"name":173,"class":6},"Qilu Hospital of Shandong University",{"name":175,"class":6},"Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University",{"name":177,"class":6},"Zhengzhou Central Hospital",{"name":179,"class":6},"Second Affiliated Hospital of Nanchang University",{"name":181,"class":6},"West China Hospital",{"name":183,"class":6},"Shanghai Tongji Hospital, Tongji University School of Medicine",{"name":185,"class":6},"Weifang People's Hospital",{"name":187,"class":6},"Huang Shan People's Hospital",{"name":189,"class":6},"Jinhua Central Hospital",{"name":191,"class":6},"RenJi Hospital",{"name":193,"class":6},"People's Hospital of Quzhou",{"name":195,"class":6},"Taizhou Hospital",{"name":197,"class":198},"the second people's of kaifeng","UNKNOWN","100658640","phase-4-tobramycin-nebulization-to-prevent-multidrug-resistant-ventilator-associated-pneumonia-100658640",false,"NCT07856355","Tobramycin Nebulization to Prevent Multidrug-Resistant Ventilator-Associated Pneumonia","Tobramycin Nebulization to Prevent Multidrug-Resistant Ventilator-Associated Pneumonia: A Prospective, Multicenter, Double-Blind, Randomized Controlled Trial","TOP-MDRVAP","Inclusion Criteria:\n\n1. Age ≥18 years at enrollment.\n2. 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.\n3. At least one of the following risk factors for multidrug-resistant (MDR) bacterial infection:\n\n   3.1 Exposure to systemic antibiotics for ≥24 hours within the 30 days before enrollment.\n\n   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\u002FL.\n\n   3.4 Moderate-to-severe acute respiratory distress syndrome (ARDS), according to the Berlin definition, with a PaO2\u002FFiO2 ratio ≤200 mmHg and positive end-expiratory pressure (PEEP) ≥5 cm H2O.\n\n   3.5 Current renal replacement therapy, including continuous renal replacement therapy or intermittent hemodialysis.\n\n   3.6 A history of MDR bacterial colonization or infection within the previous 12 months, documented by clinical culture.\n4. Written informed consent obtained from the patient or the patient's legally authorized representative.\n\nExclusion Criteria:\n\n1. Suspected or confirmed ventilator-associated pneumonia (VAP) on the day of enrollment, based on the attending physician's clinical judgment.\n2. Continuous invasive mechanical ventilation for more than 96 hours before enrollment.\n3. Planned extubation within the next 24 hours.\n4. Previous tracheostomy.\n5. A history of allergy to tobramycin or any other aminoglycoside antibiotic.\n6. 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.\n7. Chronic kidney disease (stages 4-5) with a baseline estimated glomerular filtration rate (eGFR) ≤30 mL\u002Fmin\u002F1.73 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\u002FL, urine output \\\u003C0.3 mL\u002Fkg\u002Fhour 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.\n8. Expected survival of no more than 48 hours, as assessed by the attending physician.\n9. Pregnancy, indicated by a positive serum or urine human chorionic gonadotropin (hCG) test, or breastfeeding.\n10. Concurrent participation in another interventional clinical study involving nebulized antibiotics or other ventilator-associated pneumonia prevention interventions.","ALL","18 Years",{"count":210,"type":211},574,"ESTIMATED","INTERVENTIONAL",[214],"PHASE4","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.\n\nThe 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.\n\nParticipants 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.\n\nBoth 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.\n\nThe 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.\n\nParticipants 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.",[217],"Pneumonia, Ventilator-Associated",[219,220,221,222,223,224,225,226],"Tobramycin","Inhaled Antibiotics","Antibiotic Prophylaxis","Ventilator-Associated Pneumonia","Multidrug-Resistant Bacteria","Invasive Mechanical Ventilation","Critically Ill Patients","Intensive Care Unit","NOT_YET_RECRUITING","2026-09-23",{"date":230,"type":231},"2026-10-02","ACTUAL",{"date":233,"type":211},"2026-10-07",{"date":235,"type":211},"2029-01-29",{"name":5,"class":6},1]