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
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)
Design
Parallel group randomized phase 3 on 70 patients trial with Random allocation software double blinded
Settings and conduct
70 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
Participants/Inclusion and exclusion criteria
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
Intervention groups
35 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
Main outcome variables
Average CPIS score reduction in two groups on days 1, 5, 7 (or stop intervention day)
General information
Reason for update
Acronym
IRCT registration information
IRCT registration number:IRCT20100107003014N26
Registration date:2023-11-13, 1402/08/22
Registration timing:registered_while_recruiting
Last update:2023-11-13, 1402/08/22
Update count:1
Registration date
2023-11-13, 1402/08/22
Registrant information
Name
Shahram Ala
Name of organization / entity
Mazandaran University of Medical Sciences
Country
Iran (Islamic Republic of)
Phone
+98 15 1354 3083
Email address
sala@mazums.ac.ir
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2023-10-23, 1402/08/01
Expected recruitment end date
2024-04-20, 1403/02/01
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
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
Public title
Efficacy of levofloxacin and colistin inhalation form in treatment of pneumonia
Purpose
Treatment
Inclusion/Exclusion criteria
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
Age
From 18 years old to 80 years old
Gender
Both
Phase
1-2
Groups that have been masked
Participant
Investigator
Outcome assessor
Data analyser
Sample size
Target sample size:
70
More than 1 sample in each individual
Number of samples in each individual:
35
35 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.
Randomization (investigator's opinion)
Randomized
Randomization description
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.
Blinding (investigator's opinion)
Double blinded
Blinding description
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.
Placebo
Not used
Assignment
Parallel
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Ethics department of Mazandaran University of Medical Sciences
Street address
Moallem square, Sari, Mazandaran, Iran
City
Sari
Province
Mazandaran
Postal code
33971- 48157
Approval date
2023-09-23, 1402/07/01
Ethics committee reference number
IR.MAZUMS.REC.1402.423
Health conditions studied
1
Description of health condition studied
Ventilator associated pneumonia (VAP) caused by multidrug resistant pathogens
ICD-10 code
J95.851
ICD-10 code description
Ventilator associated pneumonia
Primary outcomes
1
Description
Average CPIS score reduction in two groups
Timepoint
days 1, 5, 7 (or stop intervention day)
Method of measurement
CPIS scoring table
Secondary outcomes
1
Description
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
Timepoint
Days 1, 3, 5 and 7 of intervention
Method of measurement
Blood sample sent to the laboratory
2
Description
Registration of bronchospasm complication occurred during treatment in two groups of patients
Timepoint
During the intervention
Method of measurement
Airway resistance in the ventilator
3
Description
Improvement rate in compliance and resistance of the respiratory tract in patients of two groups
Timepoint
Days 1, 3, 5 and 7 of intervention
Method of measurement
Ventilator data and calculation according to the formula
4
Description
Mortality rate of patients in two groups until the duration of hospitalization in ICU
Timepoint
During the intervention up to the duration of ICU stay
Method of measurement
Patient database
5
Description
The 28-day mortality rate of patients in two groups
Timepoint
28 days after pneumonia caused by mechanical ventilation
Method of measurement
Patient database
Intervention groups
1
Description
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
Category
Treatment - Drugs
2
Description
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
Category
Treatment - Drugs
Recruitment centers
1
Recruitment center
Name of recruitment center
Imam Khomeini hospital
Full name of responsible person
Shahram Ala
Street address
Razi street
City
Sari
Province
Mazandaran
Postal code
3313148166
Phone
+98 11 6333 1700
Email
info@emamhospital.ir
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
Mazandaran University of Medical Sciences
Full name of responsible person
Pedram Ebrahimnejad
Street address
Moallem square, vice chancellor for research and technology of Mazandaran university of medical sciences
City
Sari
Province
Mazandaran
Postal code
4815733971
Phone
+98 11 3325 7230
Email
pajooheshi@mazums.ac.ir
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Mazandaran University of Medical Sciences
Proportion provided by this source
100
Public or private sector
Public
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Academic
Person responsible for general inquiries
Contact
Name of organization / entity
Mazandaran University of Medical Sciences
Full name of responsible person
Shahram Ala
Position
Professor
Latest degree
Specialist
Other areas of specialty/work
Medical Pharmacy
Street address
Payambar Azam University Complex, Mazandaran University of Medical Sciences, Faculty of Pharmacy, Km 18 Khazar Abad Road, Sari, Mazandaran,
City
Sari
Province
Mazandaran
Postal code
4815733971
Phone
+98 11 3354 3083
Email
sala@mazums.ac.ir
Person responsible for scientific inquiries
Contact
Name of organization / entity
Mazandaran University of Medical Sciences
Full name of responsible person
Shahram Ala
Position
Professor
Latest degree
Specialist
Other areas of specialty/work
Medical Pharmacy
Street address
Payambar Azam University Complex, Mazandaran University of Medical Sciences, Faculty of Pharmacy, Km 18 Khazar Abad Road, Sari, Mazandaran
City
Sari
Province
Mazandaran
Postal code
4815733971
Phone
+98 11 3354 3083
Email
sala@mazums.ac.ir
Person responsible for updating data
Contact
Name of organization / entity
Mazandaran University of Medical Sciences
Full name of responsible person
Shahram Ala
Position
Professor
Latest degree
Specialist
Other areas of specialty/work
Medical Pharmacy
Street address
18km Khazar Abad Road,Payambar Azam University Complex, Mazandaran University of Medical Sciences, Faculty of Pharmacy
City
Sari
Province
Mazandaran
Postal code
4815733971
Phone
+98 11 3354 3083
Email
sala@mazums.ac.ir
Sharing plan
Deidentified Individual Participant Data Set (IPD)
Undecided - It is not yet known if there will be a plan to make this available
Study Protocol
Undecided - It is not yet known if there will be a plan to make this available
Statistical Analysis Plan
Undecided - It is not yet known if there will be a plan to make this available
Informed Consent Form
Undecided - It is not yet known if there will be a plan to make this available
Clinical Study Report
Undecided - It is not yet known if there will be a plan to make this available
Analytic Code
Undecided - It is not yet known if there will be a plan to make this available
Data Dictionary
Undecided - It is not yet known if there will be a plan to make this available