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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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History
# Registration date Revision Id
2 2024-10-12, 1403/07/21 317666
1 2023-11-13, 1402/08/22 285137
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  • Protocol summary

    Parallel group randomized phase 3 on 70 patients trial with Random allocation software double blinded
    Parallel group randomized phase 3 on 46 patients trial with Random allocation software double blinded
    تصادفی سازی، دو سوکور، گروه های موازی، فاز3 در 70 بیمار، بلوک بندی با نرم افزار Random allocation
    تصادفی سازی، دو سوکور، گروه های موازی، فاز3 در 46 بیمار، بلوک بندی با نرم افزار Random allocation
    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
    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
    70 بیمار بیمارستان امام خمینی بعد از کسب رضایتنامه از بستگان درجه اول تشخیص VAP و تجویز دارو توسط پزشکان طرح بر اساس کدهای مشخص ثبت اطلاعات دموگرافیک، WBC ،ESR ،CRP، BUN، SCr، مدت اینتوباسیون قبل بروز پنومونی، PCT،CPIS ،APACHE II score ،SOFA score ، ABG، کمپلیانس و مقاومت مسیر تنفسی روز اول ویال ها تولید یک شرکت داروسازی و تلاش در مشابهت سازی ظاهر آماده سازی توسط پرستار بخش عدم اطلاع دستیار بالینی و ارزیاب از نوع دارو مداخله طبق پروتکل ذکر شده ثبت WBC، ESR، CRP،BUN ،SOFA score ، SCr، ABG، کمپلیانس و مقاومت مسیر تنفسی در روزهای1، 3، 5 و 7 مطالعه CPIS در روزهای 1، 5 و 7 (یا روز قطع مداخله) اخذ نمونه مجدد ترشحات تنفسی روز پایانی اندازه گیری پروکلسی تونین ابتدا و انتهای مداخله
    46 بیمار بیمارستان امام خمینی بعد از کسب رضایتنامه از بستگان درجه اول تشخیص VAP و تجویز دارو توسط پزشکان طرح بر اساس کدهای مشخص ثبت اطلاعات دموگرافیک، WBC ،ESR ،CRP، BUN، SCr، مدت اینتوباسیون قبل بروز پنومونی، PCT،CPIS ،APACHE II score ،SOFA score ، ABG، کمپلیانس و مقاومت مسیر تنفسی روز اول ویال ها تولید یک شرکت داروسازی و تلاش در مشابهت سازی ظاهر آماده سازی توسط پرستار بخش عدم اطلاع دستیار بالینی و ارزیاب از نوع دارو مداخله طبق پروتکل ذکر شده ثبت WBC، ESR، CRP،BUN ،SOFA score ، SCr، ABG، کمپلیانس و مقاومت مسیر تنفسی در روزهای1، 3، 5 و 7 مطالعه CPIS در روزهای 1، 5 و 7 (یا روز قطع مداخله) اخذ نمونه مجدد ترشحات تنفسی روز پایانی اندازه گیری پروکلسی تونین ابتدا و انتهای مداخله
    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
    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
    35 بیمار هر گروه نبولایزر اولتراسوند کلیستین استنشاقی: 2 میلیون واحد هر 8 ساعت لووفلوکساسین استنشاقی: ویال 250 میلی گرم هر 12 ساعت هر 2 گروه: انفوزیون مروپنم 1 گرم هر 8 ساعت و کلیستین 9 میلیون واحد بارگیری و 4.5 میلیون واحد هر 12 ساعت تا 7 روز تعدیل دوز درصورت بروز اختلال کلیوی
    23 بیمار هر گروه نبولایزر اولتراسوند کلیستین استنشاقی: 2 میلیون واحد هر 8 ساعت لووفلوکساسین استنشاقی: ویال 250 میلی گرم هر 12 ساعت هر 2 گروه: انفوزیون مروپنم 1 گرم هر 8 ساعت و کلیستین 9 میلیون واحد بارگیری و 4.5 میلیون واحد هر 12 ساعت تا 7 روز تعدیل دوز درصورت بروز اختلال کلیوی

  • General information

    70
    46
    35
    23
    empty
    Limitation on the number of eligible patients and implementation facilities of the clinical trial
    empty
    محدودیت در تعداد بیماران واجد شرایط و امکانات اجرایی کارآزمایی بالینی
    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.
    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.
    35 بیمار در گروه کلیستین استنشاقی، این دارو را با دوز 2 میلیون واحد هر 8 ساعت به همراه انفوزیون مروپنم 1 گرم هر 8 ساعت به مدت 3 ساعت و انفوزیون کلیستین با دوز 9 میلیون واحد در ابتدا و سپس 4/5 میلیون واحد هر 12 ساعت به مدت 1 ساعت تا 7 روز دریافت خواهند کرد. 35 بیمار در گروه لووفلوکساسین استنشاقی، ویال تزریقی این دارو را با دوز 250 میلی گرم هر 12 ساعت به کمک نبولایزر اولتراسوند به همراه انفوزیون مروپنم 1 گرم هر 8 ساعت به مدت 3 ساعت و انفوزیون کلیستین با دوز 9 میلیون واحد در ابتدا و سپس 4/5 میلیون واحد هر 12 ساعت به مدت 1 ساعت تا 7 روز دریافت خواهند کرد.
    23 بیمار در گروه کلیستین استنشاقی، این دارو را با دوز 2 میلیون واحد هر 8 ساعت به همراه انفوزیون مروپنم 1 گرم هر 8 ساعت به مدت 3 ساعت و انفوزیون کلیستین با دوز 9 میلیون واحد در ابتدا و سپس 4/5 میلیون واحد هر 12 ساعت به مدت 1 ساعت تا 7 روز دریافت خواهند کرد. 35 بیمار در گروه لووفلوکساسین استنشاقی، ویال تزریقی این دارو را با دوز 250 میلی گرم هر 12 ساعت به کمک نبولایزر اولتراسوند به همراه انفوزیون مروپنم 1 گرم هر 8 ساعت به مدت 3 ساعت و انفوزیون کلیستین با دوز 9 میلیون واحد در ابتدا و سپس 4/5 میلیون واحد هر 12 ساعت به مدت 1 ساعت تا 7 روز دریافت خواهند کرد.

Protocol summary

Study aim
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 46 patients trial with Random allocation software double blinded
Settings and conduct
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
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
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
Main outcome variables
Average CPIS score reduction in two groups on days 1, 5, 7 (or stop intervention day)

General information

Reason for update
Limitation on the number of eligible patients and implementation facilities of the clinical trial
Acronym
IRCT registration information
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
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: 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.
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
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