Ventilator-Associated Pneumonia (VAP)CIVAPNCT06834971
Colistin Methanesulfonate Sodium Inhalation for Prophylaxis of Ventilator-Associated Pneumonia (CIVAP): A Prospective, Multicentre, Double-Blind, Randomized, Placebo-Controlled Trial
A study testing Colistimethate sodium (CMS) in people with Ventilator-Associated Pneumonia (VAP), run by Qilu Hospital of Shandong University at 1 site in China.
Trial summary
Previous studies have identified Acinetobacter baumannii (AB), Pseudomonas aeruginosa (PA), and Klebsiella pneumoniae (KP) as the predominant pathogens responsible for ventilator-associated pneumonia (VAP). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ventilator-Associated Pneumonia (VAP)
- What is being tested?
- Colistimethate sodium (CMS)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 508 participants
- Where
- 1 siteChina
- Study dates
- 15 Jul 2025to Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Participants will be enrolled if they meet the following criteria:
- Age ≥18 years;
- Mechanical ventilation for more than two consecutive days (48 hours);
- Patient has high-risk factors for multidrug-resistant bacterial infections, which meet any of the following criteria: (1)History of antibiotic exposure within 30 days; (2)Hospitalization time>5 days (120 hours); (3)Septic shock; (4) ARDS; (5)Accept renal replacement therapy; (6)Previous colonization of multidrug-resistant bacteria; 4. Informed consent of the patient or a proxy was written.
Participants will be excluded in case of:
- Suspected or confirmed VAP at the inclusion day;
- Patient ventilated through an endotracheal tube for more than four consecutive days (96 hours);
- Expected that endotracheal intubation will be removed within the next 24 hours;
- Tracheostomy;
- Allergy to CMS;
- Patients has polymyxins medication history within 7 days or clinical indication for systemic CMS therapy at the inclusion day;
- Chronic kidney failure with baseline glomerular filtration ≤30 mL/min or Stage 3 classification AKI (KDIGO) (excluding patients undergoing renal replacement therapy);
- Expected survival time not exceeding 48 hours;
- Pregnancy or breastfeeding period;
- Patients previously included in this study or are using any inhaled antibiotics or are participating in other clinical studies within 30 days.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Qilu Hospital of Shandong university
Jinan, Shandong, 250000
Hao Wang, Doctor, 18560081013, wanghao34@126.com
Wang Hao associate professor
About this study
Previous studies have identified Acinetobacter baumannii (AB), Pseudomonas aeruginosa (PA), and Klebsiella pneumoniae (KP) as the predominant pathogens responsible for ventilator-associated pneumonia (VAP). The challenge of drug resistance, especially against carbapenem is intensifying, with variations noted across different regions. Multidrug-resistant organisms associated VAP (MDR-VAP) are increasing in frequency and are associated with significant morbidity, mortality, therefore imposes a heavy burden on the healthcare system. Colistin methanesulfonate sodium (CMS) has shown effectiveness against gram-negative bacteria, including carbapenem-resistant organisms (CRO) such as carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Pseudomonas aeruginosa (CRPA), and carbapenem-resistant Klebsiella pneumoniae (CRKP). This trial aims to evaluate the efficacy of a 3-day course of inhaled CMS in lowering the incidence of VAP among patients undergoing invasive mechanical ventilation for at least two days and at high risk of MDR-VAP.
Read the detailed description
Ventilator-Associated Pneumonia (VAP) is defined as pneumonia that develops 48-72 hours or more following the initiation of mechanical ventilation. It is a critical infection acquired in the Intensive Care Unit (ICU), significantly contributing to increased mortality rates, extended ICU stays, and elevated healthcare costs for patients on ventilators[1]. VAP is reported to affect 5-40% of patients receiving mechanical ventilation, with an average incidence of 20-25%. This proportion has been exacerbated in recent years by the COVID-19 pandemic[2-4]. A meta-analysis encompassing 195 studies found that the overall cumulative incidence of VAP in mainland China is 23.8% (95% CI 20.6-27.2%)[5].
Numerous risk factors, such as prolonged mechanical ventilation, advanced age, supine body position, prior antibiotic use, and various comorbidities, in addition to the endotracheal intubation itself, have been associated with the development of VAP[6, 7]. VAP results from the invasion of pulmonary parenchyma by pathogenic bacteria, which overwhelm the host's weakened defense capability. The primary sources of these bacteria include oropharyngeal colonization, secretions around the endotracheal tube cuff, and biofilm formation on the tracheal tube. The infectious process initiates at the time of intubation and progresses over several days. Reports indicate that the daily risk of VAP peaks between days 5 and 9 of incubation, underscoring the need for early preventive measures[8]. Despite decades of research highlighting interventions such as patient positioning adjustments, daily awakening and weaning protocols, oral decontamination, and systemic antibiotics to reduce VAP incidence, the burden remains unacceptably high.
Systemic antibiotics are commonly used for both treatment and prevention of VAP. However, the risk of resistant bacteria selection is a significant concern. A meta-analysis of six trials indicated that prophylactic antibiotics administered via nebulization effectively reduced VAP occurrence without increasing the risk of multidrug resistant (MDR) pathogen-related VAP[9]. Another Meta-Analysis consisting seven RCTs also confirmed that pro- phylactic antibiotics delivered via the respiratory tract reduced the risk of VAP, particularly for those treated with nebulized aminoglycosides[10]. Additionally, a short course of aerosolized ceftazidime significantly decreased VAP frequency in critically ill trauma patients without adversely affecting bacterial pathogen profiles and sensitivity patterns[11]. Recently, a study of 3-day course of inhaled amikacin was shown to effectively reduce the incidence of VAP[12, 13]. Stephan Ehrmann's team confirmed the possibility of inhaled amikacin to lessen the VAP burden during a 28-day follow-up period. This study provides us with excellent inspiration and suggests promising prospects for the use of nebulized antibiotics in preventing VAP. However, there are still more than 10% of patients who have amikacin resistance that can not be covered among all participants and the burden of MDR-VAP has becoming increasingly heavy with variations across different regions. Data from China Antimicrobial Surveillance Network (CHINET 2024) shows the resistance rates of Acinetobacter baumannii (AB), Klebsiella pneumoniae (KP), and Pseudomonas aeruginosa (PA) to amikacin are 49.5%, 15.5%, and 3.4%, respectively. In contrast, the resistance rates of carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Klebsiella pneumoniae (CRKP), and carbapenem-resistant Pseudomonas aeruginosa (CRPA) to amikacin are as high as 77.4%, 67.1%, and 11.4%, respectively.
Given the effectiveness of CMS against gram-negative bacteria including carbapenem-resistant organisms (CRO), we are optimistic about the potential of nebulized CMS inhalation to prevent VAP. So we designed the study to evaluate the efficacy and safety of prophylactic CMS nebulization in preventing VAP among incubated patients at high risk of MDR-VAP. We hypothesize that administering a 3-day course of pre-emptive inhaled CMS after 2 days of ventilation will reduce the subsequent incidence of VAP.
- Conditions
- Ventilator-Associated Pneumonia (VAP)
- Being tested
- Colistimethate sodium (CMS)
- Keywords
- colistin, prevention, nebulization
- Medical subject headings
- Pneumonia, Ventilator-Associated
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Colistimethate sodium (CMS)Drug
CMS (colistimethate sodium, 75mg, solubilized in 4 mL 0.9% saline), twice daily. Nebulization will be performed using a vibrating mesh nebulizer (Aeroneb solo, Aerogen, Galway, Ireland) placed in the inspiratory limb of the ventilator tubing, behind the Y-piece, and continued until the nebulizer deposit becomes dry for three consecutive days of mechanical ventilation. To ensure the experiment is conducted under blind conditions, the Nebulizer will be covered by stickers. A filter will be placed on the expiratory limb to protect the ventilator.
| Study group | Role | What they receive |
|---|---|---|
| CMS group | Experimental | Participants were randomly assigned to receive either CMS (75mg caculated as colistin base activity(CBA), solubilized in 4 mL 0.9% saline) twice daily. Nebulization will be performed using a vibrating mesh nebulizer (Aeroneb solo, Aerogen, Galway, Ireland) placed in the inspiratory limb of the ventilator tubing, behind the Y-piece, and continued until the nebulizer deposit becomes dry for three consecutive days of mechanical ventilation. To ensure the experiment is conducted under blind conditions, the Nebulizer will be covered with an opaque protective cover. A filter will be placed on the expiratory limb to protect the ventilator. Receives: Drug: Colistimethate sodium (CMS) |
| NS group | No intervention | Participants were randomly assigned to receive equivalent volume of 0.9% saline (NS group), twice daily. Nebulization will be performed using a vibrating mesh nebulizer (Aeroneb solo, Aerogen, Galway, Ireland) placed in the inspiratory limb of the ventilator tubing, behind the Y-piece, and continued until the nebulizer deposit becomes dry for three consecutive days of mechanical ventilation. To ensure the experiment is conducted under blind conditions, the Nebulizer will be covered with an opaque protective cover. A filter will be placed on the expiratory limb to protect the ventilator. |
What is being measured
The primary outcome is the main question the study is designed to answer.
The incidence of a first VAP episode from randomization to day 28
calculated as the ratio of the number of patients diagnosed VAP divided by the number of randomized patients in each group
Measured: from randomization to day 28
Secondary outcomes (11)
incidence of a first MDR-VAP episode from randomization to day 28
Calculated as the ratio of the number of patients diagnosed VAP divided by the number of randomized patients in each group
Measured: from randomization to day 28
Incidence density of adjudicated VAP from randomisation to day 28
per 1000 patient-days of invasive mechanical ventilation
Measured: from randomization to day 28
Incidence of gram-negative bacteria-related VAP with in vitro susceptibility to CMS from randomisation to day 28
the incidence of ventilator-associated pneumonia due to gram-negative bacteria with in vitro susceptibility to colistin
Measured: from randomization to day 28
The number of antibiotic-days from randomisation to day 28
the sum of the number of systemic antibiotic treatments received each day
Measured: from randomization to day 28
The number of days of mechanical ventilation from randomization to day 28
the number of days of mechanical ventilation
Measured: from randomization to extubation or day 28, whichever occurs first
The number of days in the ICU and hospital from randomization to day 90
the number of days in the ICU and the hospital
Measured: from randomization to day 90
Mortality at day 28 and 90
Mortality at 28- and 90-day after randomization
Measured: from randomization to day 28 and day 90
Evaluation of nebulization safety and side effects from randomisation to day 28
Evaluation of nebulization safety and side effects: nephrotoxicity, neurotoxicity, and bronchospasm
Measured: from randomization to day 28
Incidence of CMS-resistant bacteria in tracheobronchial aspirate (TBA) or blood from randomisation to day 28
incidence of colistin-resistant bacteria in tracheobronchial aspirate (TBA) or blood
Measured: from randomization to day 28
Incidence of ventilator-associated events from randomisation to extubation or day 28, whichever occurs first
Incidence of ventilator-associated events， including ventilator-associated conditions (VACs), infection-related ventilator associated complications (IVACs), and possible VAP (PVAP).
Measured: from randomization to extubation or day 28, whichever occurs first
incidence of a first microbiologically confirmed VAP episode from randomization to day 28
Measured: from randomization to day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2025
- Study start15 Jul 2025
- Primary completionSep 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for Ventilator-Associated Pneumonia (VAP)Studies of the same condition, open and under way.
- More trials run by Qilu Hospital of Shandong UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 508 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Qilu Hospital of Shandong University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Wang Hao, Qilu Hospital of Shandong University
- Investigators
- Hao Wang, Professor, Study director, Qilu Hospital of Shandong University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06834971
- Sponsor's protocol ID
- Qilu Wang Hao
- Acronym
- CIVAP
- Status last verified
- May 2026
- First submitted
- 13 Feb 2025
- Last updated
- 19 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Study protocol and informed consent form will be shared with other researchers when start this trial.
Publications
Wu Z, Zhang S, Cao Y, Wang Q, Sun K, Zheng X. Comparison of the clinical efficacy and toxicity of nebulized polymyxin monotherapy and combined intravenous and nebulized polymyxin for the treatment of ventilator-associated pneumonia caused by carbapenem-resistant gram-negative bacteria: a retrospective cohort study. Front Pharmacol. 2023 Aug 16;14:1209063. doi: 10.3389/fphar.2023.1209063. eCollection 2023.
PubMed 37663252Povoa FCC, Cardinal-Fernandez P, Maia IS, Reboredo MM, Pinheiro BV. Effect of antibiotics administered via the respiratory tract in the prevention of ventilator-associated pneumonia: A systematic review and meta-analysis. J Crit Care. 2018 Feb;43:240-245. doi: 10.1016/j.jcrc.2017.09.019. Epub 2017 Sep 18.
PubMed 28942198Lu Q, Luo R, Bodin L, Yang J, Zahr N, Aubry A, Golmard JL, Rouby JJ; Nebulized Antibiotics Study Group. Efficacy of high-dose nebulized colistin in ventilator-associated pneumonia caused by multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii. Anesthesiology. 2012 Dec;117(6):1335-47. doi: 10.1097/ALN.0b013e31827515de.
PubMed 23132092Biswas S, Brunel JM, Dubus JC, Reynaud-Gaubert M, Rolain JM. Colistin: an update on the antibiotic of the 21st century. Expert Rev Anti Infect Ther. 2012 Aug;10(8):917-34. doi: 10.1586/eri.12.78.
PubMed 23030331Yu Z, Qin W, Lin J, Fang S, Qiu J. Antibacterial mechanisms of polymyxin and bacterial resistance. Biomed Res Int. 2015;2015:679109. doi: 10.1155/2015/679109. Epub 2015 Jan 15.
PubMed 25664322Zhang X, Cui X, Jiang M, Huang S, Yang M. Nebulized colistin as the adjunctive treatment for ventilator-associated pneumonia: A systematic review and meta-analysis. J Crit Care. 2023 Oct;77:154315. doi: 10.1016/j.jcrc.2023.154315. Epub 2023 Apr 28.
PubMed 37120926Hu JN, Hu SQ, Li ZL, Bao C, Liu Q, Liu C, Xu SY. Risk factors of multidrug-resistant bacteria infection in patients with ventilator-associated pneumonia: A systematic review and meta-analysis. J Infect Chemother. 2023 Oct;29(10):942-947. doi: 10.1016/j.jiac.2023.06.008. Epub 2023 Jun 13.
PubMed 37321291Ranzani OT, Niederman MS, Torres A. Ventilator-associated pneumonia. Intensive Care Med. 2022 Sep;48(9):1222-1226. doi: 10.1007/s00134-022-06773-3. Epub 2022 Jun 30. No abstract available.
PubMed 35771252Xie J, Yang Y, Huang Y, Kang Y, Xu Y, Ma X, Wang X, Liu J, Wu D, Tang Y, Qin B, Guan X, Li J, Yu K, Liu D, Yan J, Qiu H. The Current Epidemiological Landscape of Ventilator-associated Pneumonia in the Intensive Care Unit: A Multicenter Prospective Observational Study in China. Clin Infect Dis. 2018 Nov 13;67(suppl_2):S153-S161. doi: 10.1093/cid/ciy692.
PubMed 30423055Ding X, Ma X, Gao S, Su L, Shan G, Hu Y, Chen J, Ma D, Zhang F, Zhu W, Sun G, Meng X, Ma L, Zhou X, Liu D, Du B; China National Critical Care Quality Control Center Group. Effect of ICU quality control indicators on VAP incidence rate and mortality: a retrospective study of 1267 hospitals in China. Crit Care. 2022 Dec 29;26(1):405. doi: 10.1186/s13054-022-04285-6.
PubMed 36581952Ehrmann S, Barbier F, Demiselle J, Quenot JP, Herbrecht JE, Roux D, Lacherade JC, Landais M, Seguin P, Schnell D, Veinstein A, Gouin P, Lasocki S, Lu Q, Beduneau G, Ferrandiere M, Plantefeve G, Dahyot-Fizelier C, Chebib N, Mercier E, Heuze-Vourc'h N, Respaud R, Gregoire N, Garot D, Nay MA, Meziani F, Andreu P, Clere-Jehl R, Zucman N, Azais MA, Saint-Martin M, Gandonniere CS, Benzekri D, Merdji H, Tavernier E; Reva and CRICS-TRIGGERSEP F-CRIN Research Networks. Inhaled Amikacin to Prevent Ventilator-Associated Pneumonia. N Engl J Med. 2023 Nov 30;389(22):2052-2062. doi: 10.1056/NEJMoa2310307. Epub 2023 Oct 25.
PubMed 37888914Papazian L, Klompas M, Luyt CE. Ventilator-associated pneumonia in adults: a narrative review. Intensive Care Med. 2020 May;46(5):888-906. doi: 10.1007/s00134-020-05980-0. Epub 2020 Mar 10.
PubMed 32157357Metersky ML, Kalil AC. Management of Ventilator-Associated Pneumonia: Guidelines. Infect Dis Clin North Am. 2024 Mar;38(1):87-101. doi: 10.1016/j.idc.2023.12.004.
PubMed 38280768
Study at a glance
From the registry record, last updated by the sponsor on 19 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Colistin Methanesulfonate Sodium Inhalation for Prophylaxis of Ventilator-Associated Pneumonia (CIVAP): A Prospective, Multicentre, Double-Blind, Randomized, Placebo-Controlled Trial
- ClinicalTrials.gov ID
- NCT06834971
- Acronym / sponsor ID
- CIVAP / Qilu Wang Hao
- Conditions
- Ventilator-Associated Pneumonia (VAP)
- Keywords
- colistin, prevention, nebulization
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 508 participants (estimated)
- Lead sponsor
- Qilu Hospital of Shandong UniversityUniversity, hospital or other
- Study start
- 15 Jul 2025 (actual)
- Primary completion
- Sep 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 19 Feb 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Previous studies have identified Acinetobacter baumannii (AB), Pseudomonas aeruginosa (PA), and Klebsiella pneumoniae (KP) as the predominant pathogens responsible for ventilator-associated pneumonia (VAP). The challenge of drug resistance, especially against carbapenem is intensifying, with variations noted across different regions. Multidrug-resistant organisms associated VAP (MDR-VAP) are increasing in frequency and are associated with significant morbidity, mortality, therefore imposes a heavy burden on the healthcare system. Colistin methanesulfonate sodium (CMS) has shown effectiveness against gram-negative bacteria, including carbapenem-resistant organisms (CRO) such as carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Pseudomonas aeruginosa (CRPA), and carbapenem-resistant Klebsiella pneumoniae (CRKP). This trial aims to evaluate the efficacy of a 3-day course of inhaled CMS in lowering the incidence of VAP among patients undergoing invasive mechanical ventilation for at least two days and at high risk of MDR-VAP.
Detailed description
Ventilator-Associated Pneumonia (VAP) is defined as pneumonia that develops 48-72 hours or more following the initiation of mechanical ventilation. It is a critical infection acquired in the Intensive Care Unit (ICU), significantly contributing to increased mortality rates, extended ICU stays, and elevated healthcare costs for patients on ventilators[1]. VAP is reported to affect 5-40% of patients receiving mechanical ventilation, with an average incidence of 20-25%. This proportion has been exacerbated in recent years by the COVID-19 pandemic[2-4]. A meta-analysis encompassing 195 studies found that the overall cumulative incidence of VAP in mainland China is 23.8% (95% CI 20.6-27.2%)[5].
Numerous risk factors, such as prolonged mechanical ventilation, advanced age, supine body position, prior antibiotic use, and various comorbidities, in addition to the endotracheal intubation itself, have been associated with the development of VAP[6, 7]. VAP results from the invasion of pulmonary parenchyma by pathogenic bacteria, which overwhelm the host's weakened defense capability. The primary sources of these bacteria include oropharyngeal colonization, secretions around the endotracheal tube cuff, and biofilm formation on the tracheal tube. The infectious process initiates at the time of intubation and progresses over several days. Reports indicate that the daily risk of VAP peaks between days 5 and 9 of incubation, underscoring the need for early preventive measures[8]. Despite decades of research highlighting interventions such as patient positioning adjustments, daily awakening and weaning protocols, oral decontamination, and systemic antibiotics to reduce VAP incidence, the burden remains unacceptably high.
Systemic antibiotics are commonly used for both treatment and prevention of VAP. However, the risk of resistant bacteria selection is a significant concern. A meta-analysis of six trials indicated that prophylactic antibiotics administered via nebulization effectively reduced VAP occurrence without increasing the risk of multidrug resistant (MDR) pathogen-related VAP[9]. Another Meta-Analysis consisting seven RCTs also confirmed that pro- phylactic antibiotics delivered via the respiratory tract reduced the risk of VAP, particularly for those treated with nebulized aminoglycosides[10]. Additionally, a short course of aerosolized ceftazidime significantly decreased VAP frequency in critically ill trauma patients without adversely affecting bacterial pathogen profiles and sensitivity patterns[11]. Recently, a study of 3-day course of inhaled amikacin was shown to effectively reduce the incidence of VAP[12, 13]. Stephan Ehrmann's team confirmed the possibility of inhaled amikacin to lessen the VAP burden during a 28-day follow-up period. This study provides us with excellent inspiration and suggests promising prospects for the use of nebulized antibiotics in preventing VAP. However, there are still more than 10% of patients who have amikacin resistance that can not be covered among all participants and the burden of MDR-VAP has becoming increasingly heavy with variations across different regions. Data from China Antimicrobial Surveillance Network (CHINET 2024) shows the resistance rates of Acinetobacter baumannii (AB), Klebsiella pneumoniae (KP), and Pseudomonas aeruginosa (PA) to amikacin are 49.5%, 15.5%, and 3.4%, respectively. In contrast, the resistance rates of carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Klebsiella pneumoniae (CRKP), and carbapenem-resistant Pseudomonas aeruginosa (CRPA) to amikacin are as high as 77.4%, 67.1%, and 11.4%, respectively.
Given the effectiveness of CMS against gram-negative bacteria including carbapenem-resistant organisms (CRO), we are optimistic about the potential of nebulized CMS inhalation to prevent VAP. So we designed the study to evaluate the efficacy and safety of prophylactic CMS nebulization in preventing VAP among incubated patients at high risk of MDR-VAP. We hypothesize that administering a 3-day course of pre-emptive inhaled CMS after 2 days of ventilation will reduce the subsequent incidence of VAP.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CMS group | Experimental | Drug: Colistimethate sodium (CMS)Participants were randomly assigned to receive either CMS (75mg caculated as colistin base activity(CBA), solubilized in 4 mL 0.9% saline) twice daily. Nebulization will be performed using a vibrating mesh nebulizer (Aeroneb solo, Aerogen, Galway, Ireland) placed in the inspiratory limb of the ventilator tubing, behind the Y-piece, and continued until the nebulizer deposit becomes dry for three consecutive days of mechanical ventilation. To ensure the experiment is conducted under blind conditions, the Nebulizer will be covered with an opaque protective cover. A filter will be placed on the expiratory limb to protect the ventilator. |
| NS group | No intervention | –Participants were randomly assigned to receive equivalent volume of 0.9% saline (NS group), twice daily. Nebulization will be performed using a vibrating mesh nebulizer (Aeroneb solo, Aerogen, Galway, Ireland) placed in the inspiratory limb of the ventilator tubing, behind the Y-piece, and continued until the nebulizer deposit becomes dry for three consecutive days of mechanical ventilation. To ensure the experiment is conducted under blind conditions, the Nebulizer will be covered with an opaque protective cover. A filter will be placed on the expiratory limb to protect the ventilator. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Colistimethate sodium (CMS)CMS (colistimethate sodium, 75mg, solubilized in 4 mL 0.9% saline), twice daily. Nebulization will be performed using a vibrating mesh nebulizer (Aeroneb solo, Aerogen, Galway, Ireland) placed in the inspiratory limb of the ventilator tubing, behind the Y-piece, and continued until the nebulizer deposit becomes dry for three consecutive days of mechanical ventilation. To ensure the experiment is conducted under blind conditions, the Nebulizer will be covered by stickers. A filter will be placed on the expiratory limb to protect the ventilator. | Drug | CMS group |
Primary outcome
The incidence of a first VAP episode from randomization to day 28
Time frame: from randomization to day 28
calculated as the ratio of the number of patients diagnosed VAP divided by the number of randomized patients in each group
11 secondary outcomes
incidence of a first MDR-VAP episode from randomization to day 28
Time frame: from randomization to day 28
Incidence density of adjudicated VAP from randomisation to day 28
Time frame: from randomization to day 28
Incidence of gram-negative bacteria-related VAP with in vitro susceptibility to CMS from randomisation to day 28
Time frame: from randomization to day 28
The number of antibiotic-days from randomisation to day 28
Time frame: from randomization to day 28
The number of days of mechanical ventilation from randomization to day 28
Time frame: from randomization to extubation or day 28, whichever occurs first
The number of days in the ICU and hospital from randomization to day 90
Time frame: from randomization to day 90
Mortality at day 28 and 90
Time frame: from randomization to day 28 and day 90
Evaluation of nebulization safety and side effects from randomisation to day 28
Time frame: from randomization to day 28
Incidence of CMS-resistant bacteria in tracheobronchial aspirate (TBA) or blood from randomisation to day 28
Time frame: from randomization to day 28
Incidence of ventilator-associated events from randomisation to extubation or day 28, whichever occurs first
Time frame: from randomization to extubation or day 28, whichever occurs first
incidence of a first microbiologically confirmed VAP episode from randomization to day 28
Time frame: from randomization to day 28
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2026.
- Background: PubMed 37663252Wu Z, Zhang S, Cao Y, Wang Q, Sun K, Zheng X. Comparison of the clinical efficacy and toxicity of nebulized polymyxin monotherapy and combined intravenous and nebulized polymyxin for the treatment of ventilator-associated pneumonia caused by carbapenem-resistant gram-negative bacteria: a retrospective cohort study. Front Pharmacol. 2023 Aug 16;14:1209063. doi: 10.3389/fphar.2023.1209063. eCollection 2023.
- Background: PubMed 28942198Povoa FCC, Cardinal-Fernandez P, Maia IS, Reboredo MM, Pinheiro BV. Effect of antibiotics administered via the respiratory tract in the prevention of ventilator-associated pneumonia: A systematic review and meta-analysis. J Crit Care. 2018 Feb;43:240-245. doi: 10.1016/j.jcrc.2017.09.019. Epub 2017 Sep 18.
- Background: PubMed 23132092Lu Q, Luo R, Bodin L, Yang J, Zahr N, Aubry A, Golmard JL, Rouby JJ; Nebulized Antibiotics Study Group. Efficacy of high-dose nebulized colistin in ventilator-associated pneumonia caused by multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii. Anesthesiology. 2012 Dec;117(6):1335-47. doi: 10.1097/ALN.0b013e31827515de.
- Background: PubMed 23030331Biswas S, Brunel JM, Dubus JC, Reynaud-Gaubert M, Rolain JM. Colistin: an update on the antibiotic of the 21st century. Expert Rev Anti Infect Ther. 2012 Aug;10(8):917-34. doi: 10.1586/eri.12.78.
- Background: PubMed 25664322Yu Z, Qin W, Lin J, Fang S, Qiu J. Antibacterial mechanisms of polymyxin and bacterial resistance. Biomed Res Int. 2015;2015:679109. doi: 10.1155/2015/679109. Epub 2015 Jan 15.
- Background: PubMed 37120926Zhang X, Cui X, Jiang M, Huang S, Yang M. Nebulized colistin as the adjunctive treatment for ventilator-associated pneumonia: A systematic review and meta-analysis. J Crit Care. 2023 Oct;77:154315. doi: 10.1016/j.jcrc.2023.154315. Epub 2023 Apr 28.
- Background: PubMed 37321291Hu JN, Hu SQ, Li ZL, Bao C, Liu Q, Liu C, Xu SY. Risk factors of multidrug-resistant bacteria infection in patients with ventilator-associated pneumonia: A systematic review and meta-analysis. J Infect Chemother. 2023 Oct;29(10):942-947. doi: 10.1016/j.jiac.2023.06.008. Epub 2023 Jun 13.
- Background: PubMed 35771252Ranzani OT, Niederman MS, Torres A. Ventilator-associated pneumonia. Intensive Care Med. 2022 Sep;48(9):1222-1226. doi: 10.1007/s00134-022-06773-3. Epub 2022 Jun 30. No abstract available.
- Background: PubMed 30423055Xie J, Yang Y, Huang Y, Kang Y, Xu Y, Ma X, Wang X, Liu J, Wu D, Tang Y, Qin B, Guan X, Li J, Yu K, Liu D, Yan J, Qiu H. The Current Epidemiological Landscape of Ventilator-associated Pneumonia in the Intensive Care Unit: A Multicenter Prospective Observational Study in China. Clin Infect Dis. 2018 Nov 13;67(suppl_2):S153-S161. doi: 10.1093/cid/ciy692.
- Background: PubMed 36581952Ding X, Ma X, Gao S, Su L, Shan G, Hu Y, Chen J, Ma D, Zhang F, Zhu W, Sun G, Meng X, Ma L, Zhou X, Liu D, Du B; China National Critical Care Quality Control Center Group. Effect of ICU quality control indicators on VAP incidence rate and mortality: a retrospective study of 1267 hospitals in China. Crit Care. 2022 Dec 29;26(1):405. doi: 10.1186/s13054-022-04285-6.
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- Individual participant dataSharing planned: Yes. Study protocol and informed consent form will be shared with other researchers when start this trial.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Hao Wang, Professor study director
Qilu Hospital of Shandong University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Colistimethate sodium (CMS) in people with Ventilator-Associated Pneumonia (VAP), run by Qilu Hospital of Shandong University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 19 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Hao Wang, Professor (18560081013, wanghao34@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The incidence of a first VAP episode from randomization to day 28 (time frame: from randomization to day 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06834971, which also lists 13 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 May 2026.