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Approach for Optimizing Meropenem Therapy in Intubated and Mechanically-Ventilated, Adult Patients With Severe Gram-Negative Lower Respiratory Tract Infection (MON4STRAT)

Primary Purpose

Lower Respiratory Tract Infection

Status
Terminated
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
MON4STRAT Strategy
Control group
Sponsored by
Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lower Respiratory Tract Infection focused on measuring MON4STRAT, Treatment Drug Monitoring, Antibiotic Resistance, Beta-Lactams Resistance, Meropenem, Health Care-Asociated Infection

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Males and non-pregnant, non-lactating females, 18 years of age or older
  2. Currently intubated and mechanically-ventilated subjects in the ICU
  3. Suspicion of lower respiratory tract infection
  4. Presence of Gram-negative organism(s) by Gram stain OR by culture of pre-therapy respiratory specimen (eg, endotracheal aspirate [ETA], bronchoalveolar lavage [BAL], or mini-BAL) OR previous colonization 48 h before screening.
  5. Initial empiric antimicrobial meropenem regimen
  6. At least two risk factors for multidrug-resistant organisms
  7. Provision of written informed consent by the subject or a family member or a close relative or waiver of consent.

Exclusion Criteria:

  1. Subjects who have received antibiotic therapy for Gram-negative LRT infection for ≥ 36 hours at the time of randomization
  2. Subjects with known or suspected type 1 hypersensitivity to beta-lactam and/or cephalosporin
  3. Subjects taking valproic acid for a seizure disorder
  4. Subjects who have had a left hemisphere stroke within five days and there is an increased risk of fatal brain oedema
  5. Subjects who have cystic fibrosis, human immunodeficiency virus (HIV) infection with CD4 count <100 cell/mm3 or invasive fungal infection of the lung
  6. Neutropenia (ANC < 103 neutrophils/mm3)
  7. Bone marrow transplant.
  8. Subjects who have been on mechanical ventilation for >28 days

Sites / Locations

  • Université Libre de Bruxelles
  • Pitié Salpêtrière Hospital
  • Hospital Ramón y Cajal

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Group 1: MON4STRAT Strategy

Group 2: Conventional treatment

Arm Description

Outcomes

Primary Outcome Measures

To document the superiority of the MON4STRAT approach for reaching and maintaining a meropenem pre-determined PK-PD target when compared to conventional therapies.
The proportion of time from day 1 after randomization to end of therapy (EOT) in which the free meropenem trough concentration in serum was maintained above 8 mg/L or above 4 x MIC if antibiotic MIC > 2 and ≤ 8 mg/L, without exceeding 140 mg/L at peak level, as determined by a method of reference (HPLC).

Secondary Outcome Measures

Clinical and microbiological response rates
Time to LRT bacterial eradication, as assessed by follow-up cultures of ETA
All-cause mortality
ICU and hospital length of stay
Number of mechanical ventilation-free days, defined as the number of days of unassisted breathing

Full Information

First Posted
April 3, 2019
Last Updated
February 13, 2020
Sponsor
Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
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1. Study Identification

Unique Protocol Identification Number
NCT03915236
Brief Title
Approach for Optimizing Meropenem Therapy in Intubated and Mechanically-Ventilated, Adult Patients With Severe Gram-Negative Lower Respiratory Tract Infection
Acronym
MON4STRAT
Official Title
Prospective, Randomized, Open, Controlled, Multicenter Study to Evaluate the Safety and Efficacy of the MON4STRAT Approach for Optimizing Meropenem Therapy in Intubated and Mechanically-Ventilated, Adult Patients With Severe Gram-Negative Lower Respiratory Tract Infection MON4STRAT Study
Study Type
Interventional

2. Study Status

Record Verification Date
April 2019
Overall Recruitment Status
Terminated
Why Stopped
It was decided to discontinuate the study due to a very low recruitment.
Study Start Date
February 18, 2019 (Actual)
Primary Completion Date
July 8, 2019 (Actual)
Study Completion Date
July 29, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Antibacterial drugs are facing increasing limitations in terms of effectiveness due to emergence resistance. Improved antibacterial drug monitoring approaches are particularly needed in nosocomial infections occurring in ICU patients, including ventilator-associated pneumonia and ventilator-associated tracheobronchitis, where decreased susceptibility of the etiological organisms is observed worldwide and pharmacokinetic alterations frequently observed. No routine drug monitoring is available for betalactams at the point of care in a useful time frame (i.e., within a few hours after having collected the blood specimens). The purpose of this study is to compare MON4STRAT approach for reaching and maintaining a meropenem pre-determined PK-PD target when compared to conventional meropenem dose.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lower Respiratory Tract Infection
Keywords
MON4STRAT, Treatment Drug Monitoring, Antibiotic Resistance, Beta-Lactams Resistance, Meropenem, Health Care-Asociated Infection

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
7 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group 1: MON4STRAT Strategy
Arm Type
Experimental
Arm Title
Group 2: Conventional treatment
Arm Type
Active Comparator
Intervention Type
Device
Intervention Name(s)
MON4STRAT Strategy
Intervention Description
Meropenem infusion guided by daily Therapeutic Drug Monitoring (adjusted in order to reach predetermined PK/PD targets) using MON4STRAT device.
Intervention Type
Other
Intervention Name(s)
Control group
Intervention Description
Meropenem 1 gram infused every 8 hours over 30 minutes, consistent with standard-of-care treatment and published guidelines. Meropenem doses will be modified according to SmPC recommendations.
Primary Outcome Measure Information:
Title
To document the superiority of the MON4STRAT approach for reaching and maintaining a meropenem pre-determined PK-PD target when compared to conventional therapies.
Description
The proportion of time from day 1 after randomization to end of therapy (EOT) in which the free meropenem trough concentration in serum was maintained above 8 mg/L or above 4 x MIC if antibiotic MIC > 2 and ≤ 8 mg/L, without exceeding 140 mg/L at peak level, as determined by a method of reference (HPLC).
Time Frame
During meropenem treatment: Day1 to Day 7
Secondary Outcome Measure Information:
Title
Clinical and microbiological response rates
Time Frame
Test of cure (TOC) visit (7 to 10 days after last study drug infusion)
Title
Time to LRT bacterial eradication, as assessed by follow-up cultures of ETA
Time Frame
Days 3, 5, 7 of treatment and at the end of treatment (EOT) visit
Title
All-cause mortality
Time Frame
Day 14 and day 28
Title
ICU and hospital length of stay
Time Frame
Up to day 28
Title
Number of mechanical ventilation-free days, defined as the number of days of unassisted breathing
Time Frame
Up to day 28

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Males and non-pregnant, non-lactating females, 18 years of age or older Currently intubated and mechanically-ventilated subjects in the ICU Suspicion of lower respiratory tract infection Presence of Gram-negative organism(s) by Gram stain OR by culture of pre-therapy respiratory specimen (eg, endotracheal aspirate [ETA], bronchoalveolar lavage [BAL], or mini-BAL) OR previous colonization 48 h before screening. Initial empiric antimicrobial meropenem regimen At least two risk factors for multidrug-resistant organisms Provision of written informed consent by the subject or a family member or a close relative or waiver of consent. Exclusion Criteria: Subjects who have received antibiotic therapy for Gram-negative LRT infection for ≥ 36 hours at the time of randomization Subjects with known or suspected type 1 hypersensitivity to beta-lactam and/or cephalosporin Subjects taking valproic acid for a seizure disorder Subjects who have had a left hemisphere stroke within five days and there is an increased risk of fatal brain oedema Subjects who have cystic fibrosis, human immunodeficiency virus (HIV) infection with CD4 count <100 cell/mm3 or invasive fungal infection of the lung Neutropenia (ANC < 103 neutrophils/mm3) Bone marrow transplant. Subjects who have been on mechanical ventilation for >28 days
Facility Information:
Facility Name
Université Libre de Bruxelles
City
Bruxelles
Country
Belgium
Facility Name
Pitié Salpêtrière Hospital
City
Paris
ZIP/Postal Code
75013
Country
France
Facility Name
Hospital Ramón y Cajal
City
Madrid
ZIP/Postal Code
28034
Country
Spain

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Approach for Optimizing Meropenem Therapy in Intubated and Mechanically-Ventilated, Adult Patients With Severe Gram-Negative Lower Respiratory Tract Infection

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