Clinical trial NCT03915236: Approach for Optimizing Meropenem Therapy in Intubated and Mechanically-Ventilated, Adult Patients With Severe Gram-Negative Lower Respiratory Tract Infection
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
Overall status: TERMINATED
Phase: NA
Conditions: Lower Respiratory Tract Infection
Keywords: MON4STRAT
Treatment Drug Monitoring
Antibiotic Resistance
Beta-Lactams Resistance
Meropenem
Health Care-Asociated Infection
Lead sponsor: Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
Sponsor class: OTHER
First posted: 2019-04-16
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: To document the superiority of the MON4STRAT approach for reaching and maintaining a meropenem pre-determined PK-PD target when compared to conventional therapies.
timeFrame: During meropenem treatment: Day1 to Day 7
Secondary outcomes:
measure: Clinical and microbiological response rates
timeFrame: Test of cure (TOC) visit (7 to 10 days after last study drug infusion)
measure: Time to LRT bacterial eradication, as assessed by follow-up cultures of ETA
timeFrame: Days 3, 5, 7 of treatment and at the end of treatment (EOT) visit
measure: All-cause mortality
timeFrame: Day 14 and day 28
measure: ICU and hospital length of stay
timeFrame: Up to day 28
measure: Number of mechanical ventilation-free days, defined as the number of days of unassisted breathing
timeFrame: Up to day 28
Other outcomes:
Locations:
city: Bruxelles
country: Belgium
facility: Université Libre de Bruxelles
city: Paris
country: France
facility: Pitié Salpêtrière Hospital
city: Madrid
country: Spain
facility: Hospital Ramón y Cajal
Study officials:
References: