Carbapenem-Resistant Enterobacteriaceae InfectionPhase 2/3ABOVENCT04876430
Best Available Therapy With or Without Meropenem for Bloodstream Infections by Enterobacterales With High Level of Resistance to Carbapenems
A Phase 2/3 study testing Meropenem in people with Carbapenem-Resistant Enterobacteriaceae Infection and Bloodstream Infection, run by Hospital de Clinicas de Porto Alegre at 2 sites in Brazil.
Trial summary
Enterobacterales resistant to carbapenem are cause of severe concern in hospital-acquired infections since therapeutic options are limited. Recently approved drugs, such as bela-lactam/beta-lactamase inhibitor, have been the drug of choice. However, its use is limited in low- and middle-income countries. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carbapenem-Resistant Enterobacteriaceae Infection, Bloodstream Infection
- What is being tested?
- Meropenem
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 2 sitesBrazil
- Study dates
- 4 May 2021to 7 Mar 2022
- Phase
- Phase 2/3
- 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
- Primary or secondary bloodstream infections by any specie of the Enterobacterales family with minimum inhibitory concentration (MIC) for meropenem >32mg/L;
- Agreement of the assistant team with the inclusion of the patient in the study;
- Agreement by the patient or legal guardian to sign the informed consent form.
Who cannot join
- Known pregnancy;
- Patients belonging to the population deprived of their liberty;
- Known allergy to meropenem;
- Use of ceftazidime-avibactam (or any other new antimicrobial agent that become available in Brazil during the study period) for the treatment of the current infection;
- Infection by an Enterobacterales isolates without in vitro susceptibility to at least one antimicrobial drug;
- Bloodstream co-infection by another gram negative bacilli;
Show all 9Show fewer
- Concomitant infection at any site by a pathogen which meropenem is indicated;
- Neutropenia (<1000 neutrophils cells/mm3)
- Death expected within 48 hours of eligibility assessment.
Trial locations and contacts
2 sites in 1 country.
Brazil2 sites
Hospital de Clínicas de Porto Alegre
Porto Alegre, Rio Grande do Sul, 90035-903
Hospital São Lucas da Pontifícia Universidade Católica do Rio Grande do Sul
Porto Alegre, Rio Grande do Sul, 90619-900
About this study
Official title: Open-label Randomized Clinical Trial Comparing Best Available Therapy With or Without Meropenem for Bloodstream Infections by Enterobacterales With Minimal Inhibitory Concentrations for Meropenem Above 32mg/L
Enterobacterales resistant to carbapenem are cause of severe concern in hospital-acquired infections since therapeutic options are limited. Recently approved drugs, such as bela-lactam/beta-lactamase inhibitor, have been the drug of choice. However, its use is limited in low- and middle-income countries. Thus, therapy of these infections mostly relies on polymyxins and other old drugs.
The role of adjuvant carbapenem therapy in combination with polymyxins, aminoglycosides and other drugs is under investigation. From a pharmacokinetic/pharmacodynamic (PK/PD), there is an elevated probability that high-dose, extended infusion administered meropenem reach the PK/PD target of 40% above the minimal inhibitory concentration (MIC) of the pathogen when the MIC is 32mg/L or lower (non-susceptible isolates have MICs of 4mg/L or higher). However, the MIC is not routinely determined in clinical laboratories. In addition, high-level (above 32mg/L) resistance to carbapenems have been reported in many studies.
This open-label, randomized clinical trial aim to assess if the addition of meropenem to the best available therapy can increase the number of days alive and free of hospitalization in patients with bloodstream infections by Enterobacterales with MIC of meropenem above 32mg/L.
- Being tested
- Meropenem
- Keywords
- carbapenem, carbapenemase, polymyxins, treatment, carbapenem resistance
- Medical subject headings
- Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MeropenemDrug
Meropenem 2g every 8h for patients with glomerular filtration rate (GFR) equal or higher that 50 mL/min. Dose adjustment is recommended for patients with GFR < 50mL/min.
| Study group | Role | What they receive |
|---|---|---|
| Meropenem plus Best Available Therapy plus | Experimental | Meropenem 2g every 8 hours combined with the best available therapy (BAT). BAT will be defined according to the susceptibility profile and decision of the assistant team before randomization and should include at least one of the antimicrobials that, usually, have in vitro activity against carbapenem-resistant Enterobacterales isolates.
1. Polymyxin B or colistimethate;
2. Amikacin or gentamicin;
3. Tigecycline;
4. Another antimicrobial with in vitro susceptibility.
Doses will be defined by the assistant team. Receives: Drug: Meropenem |
| Best Available Therapy | No intervention | The best available therapy will be defined according to the susceptibility profile and decision of the assistant team before randomization and should include at least one of the antimicrobials that, usually, have in vitro activity against carbapenem-resistant Enterobacterales isolates. 1. Polymyxin B or colistimethate; 2. Amikacin or gentamicin; 3. Tigecycline; 4. Another antimicrobial with in vitro susceptibility. Doses will be defined by the assistant team. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Days alive and free of hospitalization
Number of days in which patients are alive and out of the hospital
Measured: 60 days
Secondary outcomes (6)
Overall mortality
Death for any cause
Measured: 14, 28 and 60 days after randomization
Antimicrobial-free days
Number of days in which patients are alive and without use of antimicrobial drugs
Measured: 60 days after randomization
Relapse of infection
Presence of infection with isolation of the same bacteria between 14 and 60 days after randomization.
Measured: 60 days after randomization
Clostridioides difficile infection
Incidence of Clostridioides difficile infection
Measured: 60 days after randomization
Acute Kidney Injury
Incidence of Acute Kidney Injury, according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria
Measured: 14 days after randomization
Meropenem-related adverse effects
Incidence of adverse effects related to meropenem, such as neurological toxicity and hypersensitivity reactions
Measured: 14 days after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2021
- Study start4 May 2021
- Primary completion7 Mar 2022
- Study completion7 Mar 2022
Why it stopped: Very low frequency of recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Carbapenem-Resistant Enterobacteriaceae InfectionStudies of the same condition, open and under way.
- More trials run by Hospital de Clinicas de Porto AlegreThe sponsor's other registered studies.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospital de Clinicas de Porto Alegre
- Sponsor type
- University, hospital or other
- Collaborators
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Responsible party
- Principal investigator, Alexandre Prehn Zavascki, Hospital de Clinicas de Porto Alegre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04876430
- Sponsor's protocol ID
- 2019-0401
- Acronym
- ABOVE
- Status last verified
- Aug 2022
- First submitted
- 3 May 2021
- Last updated
- 3 Aug 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open-label Randomized Clinical Trial Comparing Best Available Therapy With or Without Meropenem for Bloodstream Infections by Enterobacterales With Minimal Inhibitory Concentrations for Meropenem Above 32mg/L
- ClinicalTrials.gov ID
- NCT04876430
- Acronym / sponsor ID
- ABOVE / 2019-0401
- Keywords
- carbapenem, carbapenemase, polymyxins, treatment, carbapenem resistance
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Very low frequency of recruitment
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Hospital de Clinicas de Porto AlegreUniversity, hospital or other
- Collaborators
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Study start
- 4 May 2021 (actual)
- Primary completion
- 7 Mar 2022 (actual)
- Study completion
- 7 Mar 2022 (actual)
- First posted
- 6 May 2021 (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.
Enterobacterales resistant to carbapenem are cause of severe concern in hospital-acquired infections since therapeutic options are limited. Recently approved drugs, such as bela-lactam/beta-lactamase inhibitor, have been the drug of choice. However, its use is limited in low- and middle-income countries. Thus, therapy of these infections mostly relies on polymyxins and other old drugs.
The role of adjuvant carbapenem therapy in combination with polymyxins, aminoglycosides and other drugs is under investigation. From a pharmacokinetic/pharmacodynamic (PK/PD), there is an elevated probability that high-dose, extended infusion administered meropenem reach the PK/PD target of 40% above the minimal inhibitory concentration (MIC) of the pathogen when the MIC is 32mg/L or lower (non-susceptible isolates have MICs of 4mg/L or higher). However, the MIC is not routinely determined in clinical laboratories. In addition, high-level (above 32mg/L) resistance to carbapenems have been reported in many studies.
This open-label, randomized clinical trial aim to assess if the addition of meropenem to the best available therapy can increase the number of days alive and free of hospitalization in patients with bloodstream infections by Enterobacterales with MIC of meropenem above 32mg/L.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Meropenem plus Best Available Therapy plus | Experimental | Drug: MeropenemMeropenem 2g every 8 hours combined with the best available therapy (BAT). BAT will be defined according to the susceptibility profile and decision of the assistant team before randomization and should include at least one of the antimicrobials that, usually, have in vitro activity against carbapenem-resistant Enterobacterales isolates. 1. Polymyxin B or colistimethate; 2. Amikacin or gentamicin; 3. Tigecycline; 4. Another antimicrobial with in vitro susceptibility. Doses will be defined by the assistant team. |
| Best Available Therapy | No intervention | –The best available therapy will be defined according to the susceptibility profile and decision of the assistant team before randomization and should include at least one of the antimicrobials that, usually, have in vitro activity against carbapenem-resistant Enterobacterales isolates. 1. Polymyxin B or colistimethate; 2. Amikacin or gentamicin; 3. Tigecycline; 4. Another antimicrobial with in vitro susceptibility. Doses will be defined by the assistant team. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Primary or secondary bloodstream infections by any specie of the Enterobacterales family with minimum inhibitory concentration (MIC) for meropenem >32mg/L;
- Agreement of the assistant team with the inclusion of the patient in the study;
- Agreement by the patient or legal guardian to sign the informed consent form.
Key exclusion criteria (9 listed)
- Known pregnancy;
- Patients belonging to the population deprived of their liberty;
- Known allergy to meropenem;
- Use of ceftazidime-avibactam (or any other new antimicrobial agent that become available in Brazil during the study period) for the treatment of the current infection;
- Infection by an Enterobacterales isolates without in vitro susceptibility to at least one antimicrobial drug;
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 |
|---|---|---|
| MeropenemMeropenem 2g every 8h for patients with glomerular filtration rate (GFR) equal or higher that 50 mL/min. Dose adjustment is recommended for patients with GFR < 50mL/min. | Drug | Meropenem plus Best Available Therapy plus |
Primary outcome
Days alive and free of hospitalization
Time frame: 60 days
Number of days in which patients are alive and out of the hospital
6 secondary outcomes
Overall mortality
Time frame: 14, 28 and 60 days after randomization
Antimicrobial-free days
Time frame: 60 days after randomization
Relapse of infection
Time frame: 60 days after randomization
Clostridioides difficile infection
Time frame: 60 days after randomization
Acute Kidney Injury
Time frame: 14 days after randomization
Meropenem-related adverse effects
Time frame: 14 days after randomization
Results and safety
The study was stopped early (reason given: Very low frequency of recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2022.
Related trials for Carbapenem-Resistant Enterobacteriaceae Infection
RecruitingObservational study
Aztreonam-Avibactam in Immunocompromised Hosts
Enterobacteriaceae Infections, Carbapenem-Resistant Enterobacteriaceae Infection
RecruitingPhase 4
EaRly impAct theraPy With Ceftazidime-avibactam Via rapID Diagnostics
Blood Stream Infections, Ventilator Associated Pneumonia
Not yet recruitingObservational study
Predictive Score in Patients With Hematological Malignancies Colonized by Multidrug-resistant Enterobacteriaceae
Hemato-oncologic Patients, Colonization
Not yet recruitingPhase 2
A Clinical Trial of Resistant Potato Starch for Gut MDRO Decolonization
Clostridium Infections, Methicillin-resistant Staphylococcus Aureus (MRSA)
Active, not recruiting
Study of Probiotic Adjunctive Therapy for Decolonization of Carbapenem-Resistant Enterobacterales
Enterobacteriaceae Infections, Carrier State
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.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Meropenem in people with Carbapenem-Resistant Enterobacteriaceae Infection and Bloodstream Infection, run by Hospital de Clinicas de Porto Alegre at 2 sites in Brazil.
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 3 inclusion and 9 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 3 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Brazil. 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.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Very low frequency of 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?
Days alive and free of hospitalization (time frame: 60 days). 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 3 Aug 2022.