Lower Respiratory Tract InfectionMON4STRATNCT03915236
Approach for Optimizing Meropenem Therapy in Intubated and Mechanically-Ventilated, Adult Patients With Severe Gram-Negative Lower Respiratory Tract Infection
A study testing MON4STRAT Strategy in people with Lower Respiratory Tract Infection, run by Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal at 3 sites in 3 countries.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lower Respiratory Tract Infection
- What is being tested?
- MON4STRAT Strategy
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 3 sitesin 3 countries
- Study dates
- 18 Feb 2019to 29 Jul 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
3 sites in 3 countries.
3 sites in 3 countries
About this study
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
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
- Being tested
- MON4STRAT Strategy, Control group
- Keywords
- MON4STRAT, Treatment Drug Monitoring, Antibiotic Resistance, Beta-Lactams Resistance, Meropenem, Health Care-Asociated Infection
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MON4STRAT StrategyDevice
Meropenem infusion guided by daily Therapeutic Drug Monitoring (adjusted in order to reach predetermined PK/PD targets) using MON4STRAT device.
Control groupOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Group 1: MON4STRAT Strategy | Experimental | Not described Receives: Device: MON4STRAT Strategy |
| Group 2: Conventional treatment | Active comparator | Not described Receives: Other: Control group |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: During meropenem treatment: Day1 to Day 7
Secondary outcomes (5)
Clinical and microbiological response rates
Measured: 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
Measured: Days 3, 5, 7 of treatment and at the end of treatment (EOT) visit
All-cause mortality
Measured: Day 14 and day 28
ICU and hospital length of stay
Measured: Up to day 28
Number of mechanical ventilation-free days, defined as the number of days of unassisted breathing
Measured: Up to day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Apr 2019
- Study start18 Feb 2019
- Primary completion8 Jul 2019
- Study completion29 Jul 2019
Why it stopped: It was decided to discontinuate the study due to a very low recruitment.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lower Respiratory Tract InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03915236
- Sponsor's protocol ID
- MON4STRAT
- Other IDs
- 2018-000450-21, 2018
- Acronym
- MON4STRAT
- Status last verified
- Apr 2019
- First submitted
- 3 Apr 2019
- Last updated
- 17 Feb 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03915236
- Acronym / sponsor ID
- MON4STRAT / MON4STRAT
- Conditions
- Lower Respiratory Tract Infection
- Keywords
- MON4STRAT, Treatment Drug Monitoring, Antibiotic Resistance, Beta-Lactams Resistance, Meropenem, Health Care-Asociated Infection
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: It was decided to discontinuate the study due to a very low recruitment.
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y CajalUniversity, hospital or other
- Study start
- 18 Feb 2019 (actual)
- Primary completion
- 8 Jul 2019 (actual)
- Study completion
- 29 Jul 2019 (actual)
- First posted
- 16 Apr 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1: MON4STRAT Strategy | Experimental | Device: MON4STRAT Strategy |
| Group 2: Conventional treatment | Active comparator | Other: Control group |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MON4STRAT StrategyMeropenem infusion guided by daily Therapeutic Drug Monitoring (adjusted in order to reach predetermined PK/PD targets) using MON4STRAT device. | Device | Group 1: MON4STRAT Strategy |
| Control groupMeropenem 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. | Other | Group 2: Conventional treatment |
Primary outcome
To document the superiority of the MON4STRAT approach for reaching and maintaining a meropenem pre-determined PK-PD target when compared to conventional therapies.
Time frame: 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).
5 secondary outcomes
Clinical and microbiological response rates
Time frame: 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
Time frame: Days 3, 5, 7 of treatment and at the end of treatment (EOT) visit
All-cause mortality
Time frame: Day 14 and day 28
ICU and hospital length of stay
Time frame: Up to day 28
Number of mechanical ventilation-free days, defined as the number of days of unassisted breathing
Time frame: Up to day 28
Results and safety
The study was stopped early (reason given: It was decided to discontinuate the study due to a very low recruitment.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2020.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing MON4STRAT Strategy in people with Lower Respiratory Tract Infection, run by Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal at 3 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 17 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Belgium, France, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: It was decided to discontinuate the study due to a very low recruitment.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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. (time frame: During meropenem treatment: Day1 to Day 7). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Feb 2020.