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

NCT ID: NCT03915236

Last Updated: 2020-02-17

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 7 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-02-18
• Study Completion Date: 2019-07-29

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.

Conditions

Lower Respiratory Tract Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Group 1: MON4STRAT Strategy

Group Type: EXPERIMENTAL

MON4STRAT Strategy

Intervention Type: DEVICE

Meropenem infusion guided by daily Therapeutic Drug Monitoring (adjusted in order to reach predetermined PK/PD targets) using MON4STRAT device.

Group 2: Conventional treatment

Group Type: ACTIVE_COMPARATOR

Control group

Intervention Type: OTHER

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.

Interventions

MON4STRAT Strategy

Meropenem infusion guided by daily Therapeutic Drug Monitoring (adjusted in order to reach predetermined PK/PD targets) using MON4STRAT device.

Intervention Type: DEVICE

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.

Intervention Type: OTHER

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Université Libre de Bruxelles

Brussels, , Belgium

Pitié Salpêtrière Hospital

Paris, , France

Hospital Ramón y Cajal

Madrid, , Spain

Countries

Belgium; France; Spain

Other Identifiers

2018-000450-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MON4STRAT

Identifier Type: -

Identifier Source: org_study_id