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

NCT03915236 | Terminated

• 2 other identifiers: MON4STRAT2018-000450-21
• Study Type: interventional
• Target: 7
• Locations: 3 countries
• Sites: 3

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

Keywords

MON4STRAT; Treatment Drug Monitoring; Antibiotic Resistance; Beta-Lactams Resistance; Meropenem; Health Care-Asociated Infection

Outcome Measures

Primary Outcomes (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.

  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).

  During meropenem treatment: Day1 to Day 7

Secondary Outcomes (5)

• Clinical and microbiological response rates

  Test of cure (TOC) visit (7 to 10 days after last study drug infusion)

• 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

• All-cause mortality

  Day 14 and day 28

• 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

Study Arms (2)

Group 1: MON4STRAT Strategy

EXPERIMENTAL

Device: MON4STRAT Strategy

Group 2: Conventional treatment

ACTIVE COMPARATOR

Other: Control group

Interventions

MON4STRAT Strategy DEVICE

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

Group 1: MON4STRAT Strategy

Control group 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.

Group 2: Conventional treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal: lead

Study Sites (3)

Université Libre de Bruxelles

Brussels, Belgium

Location

Pitié Salpêtrière Hospital

Paris, 75013, France

Location

Hospital Ramón y Cajal

Madrid, 28034, Spain

Location

MeSH Terms

Interventions

Control Groups

Intervention Hierarchy (Ancestors)

Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 3, 2019
• First Posted: April 16, 2019
• Study Start: February 18, 2019
• Primary Completion: July 8, 2019
• Study Completion: July 29, 2019
• Last Updated: February 17, 2020

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1); ES (1); BE (1)