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

Not Applicable

Terminated

• Conditions: Lower Respiratory Tract Infection
• Interventions: Device: MON4STRAT Strategy; Other: Control group

• Registration Number: NCT03915236
• Lead Sponsor: 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.

Detailed Description

Not available

Study Timeline

• Study Start: 2019-02-18
• Status Verified: 2019-04
• Study First Submitted: 2019-04-03
• Study First Submitted QC: 2019-04-12
• Study First Posted: 2019-04-16
• Primary Completion: 2019-07-08
• Study Completion: 2019-07-29
• Last Update Submitted: 2020-02-13
• Last Update Posted: 2020-02-17

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 7

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1: MON4STRAT Strategy	MON4STRAT Strategy	-
Group 2: Conventional treatment	Control group	-

Primary Outcome Measures

Name	Time	Method
To document the superiority of the MON4STRAT approach for reaching and maintaining a meropenem pre-determined PK-PD target when compared to conventional therapies.	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

Name	Time	Method
ICU and hospital length of stay	Up to day 28
Number of mechanical ventilation-free days, defined as the number of days of unassisted breathing	Up to day 28
Time to LRT bacterial eradication, as assessed by follow-up cultures of ETA	Days 3, 5, 7 of treatment and at the end of treatment (EOT) visit
Clinical and microbiological response rates	Test of cure (TOC) visit (7 to 10 days after last study drug infusion)
All-cause mortality	Day 14 and day 28

Trial Locations

Locations (3)

Pitié Salpêtrière Hospital; 🇫🇷 Paris, France

Hospital Ramón y Cajal; 🇪🇸 Madrid, Spain

Université Libre de Bruxelles; 🇧🇪 Bruxelles, Belgium