MON4STRAT: Approach for Optimizing Meropenem Therapy in Intubated and Mechanically-Ventilated, Adult Patients With Severe Gram-Negative Lower Respiratory Tract Infection

Sponsor

Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal (Other)

Overall Status

Terminated

CT.gov ID

NCT03915236

Collaborator

(none)

Enrollment

Locations

Arms

5.3

Actual Duration (Months)

2.3

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

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	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

7 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 :

Feb 18, 2019

Actual Primary Completion Date :

Jul 8, 2019

Actual Study Completion Date :

Jul 29, 2019

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.

Exclusion Criteria:

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