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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)

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ClinicalTrials.gov Identifier: NCT03915236
Recruitment Status : Recruiting
First Posted : April 15, 2019
Last Update Posted : April 15, 2019
Sponsor:
Information provided by (Responsible Party):
Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal

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.


Condition or disease Intervention/treatment Phase
Lower Respiratory Tract Infection Device: MON4STRAT Strategy Other: Control group Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : February 18, 2019
Estimated Primary Completion Date : June 25, 2020
Estimated Study Completion Date : July 18, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Meropenem

Arm Intervention/treatment
Experimental: Group 1: MON4STRAT Strategy Device: MON4STRAT Strategy
Meropenem infusion guided by daily Therapeutic Drug Monitoring (adjusted in order to reach predetermined PK/PD targets) using MON4STRAT device.

Active Comparator: Group 2: Conventional treatment Other: Control group
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 Measures :
  1. To document the superiority of the MON4STRAT approach for reaching and maintaining a meropenem pre-determined PK-PD target when compared to conventional therapies. [ Time Frame: During meropenem treatment: Day1 to Day 7 ]
    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 :
  1. Clinical and microbiological response rates [ Time Frame: Test of cure (TOC) visit (7 to 10 days after last study drug infusion) ]
  2. 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 ]
  3. All-cause mortality [ Time Frame: Day 14 and day 28 ]
  4. ICU and hospital length of stay [ Time Frame: Up to day 28 ]
  5. Number of mechanical ventilation-free days, defined as the number of days of unassisted breathing [ Time Frame: Up to day 28 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03915236


Contacts
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Contact: Jean Chastre, MD 33 (0)1 42 16 38 22 jean.chastre@aphp.fr

Locations
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Belgium
Université Libre de Bruxelles Not yet recruiting
Bruxelles, Belgium
Contact: Frédérique Jacobs, MS    +32 (0)2 555 4708    frederique.jacobs@erasme.ulb.ac.be   
France
Pitié Salpêtrière Hospital Not yet recruiting
Paris, France, 75013
Contact: Jean Chastre, Professor    +33 (0)1 42 16 38 22    jean.chastre@aphp.fr   
Spain
Hospital Ramón y Cajal Recruiting
Madrid, Spain, 28034
Contact: Raúl De Pablo, MD    +34 (0) 91 336 8060    raul.depablo.uah@gmail.com   
Contact: Rafael Cantón, MD    +34 (0)9 13 36 83 30    rafael.canton@salud.madrid.org   
Sponsors and Collaborators
Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal

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Responsible Party: Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
ClinicalTrials.gov Identifier: NCT03915236     History of Changes
Other Study ID Numbers: MON4STRAT
2018-000450-21 ( EudraCT Number )
First Posted: April 15, 2019    Key Record Dates
Last Update Posted: April 15, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal:
MON4STRAT
Treatment Drug Monitoring
Antibiotic Resistance
Beta-Lactams Resistance
Meropenem
Health Care-Asociated Infection

Additional relevant MeSH terms:
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Infection
Communicable Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Meropenem
Anti-Bacterial Agents
Anti-Infective Agents