Protocol summary
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Study aim
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Efficacy comparison of adding levofloxacin and colistin inhalation form to basic regimen of colistin and meropenem in treatment of ventilator associated pneumonia (VAP) caused by multi drug resistant pathogens (MDR)
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Design
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Parallel group randomized phase 3 on 46 patients trial with Random allocation software double blinded
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Settings and conduct
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46 patients of Imam Khomeini Hospital after consent form
Drug prescription by doctors based on specific codes
Registration:
Demographic, duration of intubation before pneumonia, APACHE II: day1
WBC, ESR, CRP, BUN, SOFA, SCr, ABG, respiratory tract compliance and resistance: days 1, 3, 5 and 7
CPIS: days 1, 5 and 7 (or stop intervention day)
Respiratory secretions sample: the last day
PCT measurement: first and last day
One pharmaceutical company produce vials with attempting to same appearance
nurse preparation
Blinding for clinical assistant and evaluator
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Participants/Inclusion and exclusion criteria
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Inclusion:
18-80 years
Mechanical ventilation more than 48 hours
Pneumonia diagnosis based on 2016 guidelines of IDSA
CPIS score above 6
Positive MDR gram-negative bacteria sputum culture
Exclusion:
Pregnancy/lactation
Allergy history and major interaction with intervention drugs
Acute respiratory distress syndrome/Pulmonary tuberculosis under treatment/Cystic fibrosis
Baseline creatinine clearance less than 15 mL/min
Receiving effective antibiotics against MDR pathogens during hospitalization
Pneumonia before intubation
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Intervention groups
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23 patients in each group
Ultrasound nebulizer
Inhaled Colistin 2 million units every 8 hours or levofloxacin 250 mg every 12 hours
Both: infusion of meropenem 1 gram every 8 hours and 9 million loading units of colistin and 4.5 million units every 12 hours up to 7 days
Dose adjustment in renal failure
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Main outcome variables
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Average CPIS score reduction in two groups on days 1, 5, 7 (or stop intervention day)
General information
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Reason for update
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Limitation on the number of eligible patients and implementation facilities of the clinical trial
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Acronym
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IRCT registration information
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IRCT registration number:
IRCT20100107003014N26
Registration date:
2023-11-13, 1402/08/22
Registration timing:
registered_while_recruiting
Last update:
2024-10-17, 1403/07/26
Update count:
1
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Registration date
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2023-11-13, 1402/08/22
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Registrant information
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Recruitment status
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Recruitment complete
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Funding source
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Expected recruitment start date
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2023-10-23, 1402/08/01
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Expected recruitment end date
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2024-04-20, 1403/02/01
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Actual recruitment start date
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empty
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Actual recruitment end date
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empty
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Trial completion date
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empty
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Scientific title
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Comparison the efficacy of adding levofloxacin and colistin inhalation form to basic regimen of colistin and meropenem in treatment of ventilator associated pneumonia (VAP) caused by multidrug resistant pathogens: a double-blind randomized clinical trial
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Public title
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Efficacy of levofloxacin and colistin inhalation form in treatment of pneumonia
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Purpose
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Treatment
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Inclusion/Exclusion criteria
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Inclusion criteria:
Age older than 18 years and less than 80 years
Mechanical ventilation for more than 48 hours
Pneumonia diagnosis based on the 2016 guidelines of the Infectious Diseases Society of America (IDSA)
CPIS score above 6
Positive culture of sputum sample and growth of gram-negative bacteria resistant to treatment (MDR) (Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacteriaceae, etc.)
Exclusion criteria:
Pregnancy or breastfeeding
History of allergy to any of the drugs Colistin, Levofloxacin and Meropenem
Acute respiratory distress syndrome
Pulmonary tuberculosis disease under treatment
Cystic fibrosis disease
Major interaction of other drugs used by the patient with levofloxacin, colistin or meropenem
Baseline creatinine clearance less than 15 mL/min
History of receiving antibiotics effective against MDR pathogens during hospitalization
Presence of pneumonia before intubation
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Age
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From 18 years old to 80 years old
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Gender
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Both
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Phase
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1-2
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Groups that have been masked
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- Participant
- Investigator
- Outcome assessor
- Data analyser
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Sample size
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Target sample size:
46
More than 1 sample in each individual
Number of samples in each individual:
23
23 patients in the inhaled colistin group will receive this drug at a dose of 2 million units every 8 hours along with meropenem infusion 1 gram every 8 hours for 3 hours and colistin infusion at a dose of 9 million units at first and then 4.5 million units every 12 hours for 1 hour up to 7 days. 35 patients in the inhaled levofloxacin group will receive an injection vial of this drug at a dose of 250 mg every 12 hours with an ultrasound nebulizer along with an infusion of meropenem 1 g every 8 hours for 3 hours and an infusion of colistin at a dose of 9 million units at first and then for 4.5 million units every 12 hours for 1 hour up to 7 days.
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Randomization (investigator's opinion)
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Randomized
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Randomization description
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After selecting patients with inclusion criteria, random allocation will be done by block method. Blocking process will be done with Random allocation software. With this software, the number of blocks and the size of each block will be determined. The samples are entered into the study based on the randomly generated numbers.
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Blinding (investigator's opinion)
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Double blinded
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Blinding description
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The diagnosis of VAP will be made by special care specialists (project partners). Consumable vials for use in the nebulizer device will be purchased from a pharmaceutical company, and the appearance of the vials will be similar. The ward nurse is in charge of preparing the device and prescribed inhaler for patients to use. Covering the therapeutic intervention is done for the clinical pharmacy assistant and the person who examines the study results.
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Placebo
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Not used
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Assignment
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Parallel
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Other design features
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Ethics committees
1
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Ethics committee
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Approval date
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2023-09-23, 1402/07/01
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Ethics committee reference number
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IR.MAZUMS.REC.1402.423
Health conditions studied
1
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Description of health condition studied
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Ventilator associated pneumonia (VAP) caused by multidrug resistant pathogens
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ICD-10 code
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J95.851
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ICD-10 code description
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Ventilator associated pneumonia
Primary outcomes
1
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Description
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Average CPIS score reduction in two groups
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Timepoint
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days 1, 5, 7 (or stop intervention day)
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Method of measurement
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CPIS scoring table
Secondary outcomes
1
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Description
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The incidence of acute kidney injury (AKI) in patients of two groups during treatment according to the KDIGO definition, defined as increase in serum creatinine of 0.3 mg/dl or more within 48 hours or an increase in serum creatinine of ≥ 1.5 times
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Timepoint
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Days 1, 3, 5 and 7 of intervention
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Method of measurement
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Blood sample sent to the laboratory
2
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Description
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Registration of bronchospasm complication occurred during treatment in two groups of patients
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Timepoint
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During the intervention
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Method of measurement
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Airway resistance in the ventilator
3
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Description
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Improvement rate in compliance and resistance of the respiratory tract in patients of two groups
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Timepoint
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Days 1, 3, 5 and 7 of intervention
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Method of measurement
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Ventilator data and calculation according to the formula
4
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Description
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Mortality rate of patients in two groups until the duration of hospitalization in ICU
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Timepoint
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During the intervention up to the duration of ICU stay
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Method of measurement
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Patient database
5
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Description
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The 28-day mortality rate of patients in two groups
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Timepoint
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28 days after pneumonia caused by mechanical ventilation
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Method of measurement
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Patient database
Intervention groups
1
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Description
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Intervention group: Inhaled colistin at a dose of 2 million units every 8 hours with ultrasound nebulizer along with meropenem infusion 1 gram every 8 hours for 3 hours and colistin infusion at a dose of 9 million units loading and then 4.5 million units every 12 hours for 1 hour up to 7 days
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Category
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Treatment - Drugs
2
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Description
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Intervention group: Inhaled levofloxacin vial with a dose of 250 mg every 12 hours with ultrasound nebulizer along with meropenem infusion 1 gram every 8 hours for 3 hours and colistin infusion at a dose of 9 million units loading and then 4.5 million units every 12 hours for 1 hour up to 7 days
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Category
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Treatment - Drugs
1
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Sponsor
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Grant name
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Grant code / Reference number
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Is the source of funding the same sponsor organization/entity?
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Yes
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Title of funding source
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Mazandaran University of Medical Sciences
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Proportion provided by this source
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100
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Public or private sector
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Public
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Domestic or foreign origin
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Domestic
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Category of foreign source of funding
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empty
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Country of origin
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Type of organization providing the funding
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Academic
Sharing plan
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Deidentified Individual Participant Data Set (IPD)
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Undecided - It is not yet known if there will be a plan to make this available
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Study Protocol
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Undecided - It is not yet known if there will be a plan to make this available
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Statistical Analysis Plan
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Undecided - It is not yet known if there will be a plan to make this available
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Informed Consent Form
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Undecided - It is not yet known if there will be a plan to make this available
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Clinical Study Report
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Undecided - It is not yet known if there will be a plan to make this available
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Analytic Code
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Undecided - It is not yet known if there will be a plan to make this available
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Data Dictionary
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Undecided - It is not yet known if there will be a plan to make this available