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

Lower Respiratory Tract Infection Clinical Trial

— MON4STRAT  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03915236
• Other study ID #: MON4STRAT
• Secondary ID: 2018-000450-21
• Status: Terminated
• Phase: N/A
• Start date: February 18, 2019
• Est. completion date: July 29, 2019

Study information

• Verified date: April 2019
• Source: Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 7
• Est. completion date: July 29, 2019
• Est. primary completion date: July 8, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Communicable Diseases
• Infection
• Lower Respiratory Tract Infection
• Respiratory Tract Infections

Intervention

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

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.

Locations

Country	Name	City	State
Belgium	Université Libre de Bruxelles	Bruxelles
France	Pitié Salpêtrière Hospital	Paris
Spain	Hospital Ramón y Cajal	Madrid

Sponsors (1)

Lead Sponsor	Collaborator
Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal

Countries where clinical trial is conducted

Belgium,  France,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Clinical and microbiological response rates		Test of cure (TOC) visit (7 to 10 days after last study drug infusion)
Secondary	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
Secondary	All-cause mortality		Day 14 and day 28
Secondary	ICU and hospital length of stay		Up to day 28
Secondary	Number of mechanical ventilation-free days, defined as the number of days of unassisted breathing		Up to day 28