PneumoniaBLUE-CarbANCT03147807

BetaLACTA® Test for Early De-escalation of Empirical Carbapenems in Pulmonary, Urinary and Bloodstream Infections in ICU

A study testing betaLACTA® rapid diagnostic test in people with Pneumonia and Urinary Tract Infections, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Pneumonia, Urinary Tract Infections, Bloodstream Infection
What is being tested?: betaLACTA® rapid diagnostic test
Type of treatment: Medical device
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 75 participants
Where: 1 siteFrance
Study dates: 20 Oct 2017to 20 Oct 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

ICU patients ≥18 years.
With a suspected pneumonia (according to CPIS definition), primary blood-stream infection (according to CDC definition), and/or urinary tract infection (according to IDSA Guidelines).
And presence of ≥2 GNB/field on direct examination of a respiratory sample (quantitative bronchial aspirate with an available volume ≥ 1mL), urinary sample or blood culture.
Leading to an empirical carbapenem prescription, not administered for more than 6 hours when considering the inclusion of the patient.
Written informed consent signed by the patient / the trustworthy person / the next-of-kin / close relative, or inclusion in case of emergency and written informed consent will been signed by the patient as soon as possible.
Patients affiliated to French social security.

Who cannot join

Pregnancy.
Allergy to beta-lactams.
Patients already treated with ongoing carbapenems for another documented infection, blocking carbapenem de-escalation.
Patients included in another interventional study.
Patients in whom a procedure of withdrawing life-sustaining treatment was decided before inclusion.
Moribund patients.
Patients with aplasia.
Patients under tutorship/curatorship or patient deprived of freedom

Trial locations and contacts

1 site in 1 country.

France1 site

Anesthesiology and Critical Care Medicine Department
Paris, 75020

Other trials in France

About this study

Official title: BetaLACTA® Test-guided Early De-escalation of Empirical Carbapenems in Pulmonary, Urinary and Bloodstream Infections Diagnosed in Intensive Care Unit - BLUE¬-CarbA Study

The emergence and rapid worldwide spread of Extended- Spectrum Beta-Lactamase-producing enterobacteriaceae (ESBLE) both in hospital and community, led physicians, and notably intensivists, to prescribe more carbapenems, particularly in the most fragile patients such as ICU patients. Unfortunately, the increased carbapenem consumption favored the emergence of carbapenem resistance mechanisms. Moreover, several preliminary results suggest that carbapenem could markedly impact the human intestinal microbiota, Thus, reduction of carbapenem exposure is widely desired both by national and international antibiotic plans. Therefore, the use of rapid diagnostic tests evaluating bacterial resistance to reduce inappropriate exposure to carbapenems could be a relevant solution. Due to its good diagnostic performance, the betaLACTA® test could meet these objectives.

Experimental plan :

Randomized, open-labeled non-inferiority clinical trial involving an in vitro diagnostic medical device (close to a phase III study), comparing two parallel groups:

Experimental group: early carbapenems de-escalation since the second dose, guided by results of the betaLACTA® test performed directly on the bacterial pellet from the microbiological sample positive on direct examination.
Control group: carbapenems de-escalation guided by definitive results of the antibiotic susceptibility test obtained 48 to 72h after microbiological sampling (reference strategy).

Read the detailed description

This study is conducted on ICU patients with a suspected pneumonia, primary blood-stream infection (BSI), and/or urinary tract infection (UTI).

The primary objective of the study is to demonstrate that in ICU infections treated empirically by carbapenems and documented with GNB on direct examination of a respiratory, urinary and/or blood sample(s), the early de-escalation guided by the results of the betaLACTA® test is not inferior to the reference strategy de-escalating on antibiotic susceptibility test (AST) results obtained 48-72h after sampling, in terms of mortality at D90 and infection recurrence in ICU.

The secondary objectives are to compare the early de-escalation guided by the betaLACTA® test results to the reference strategy de-escalating on the AST results on:

The exposure to carbapenems.
The total use of ICU and hospital resources and the cost-effectiveness.
The occurrence of other infections.
The colonization of the digestive tractus of patients with 3rd generation cephalosporins (3rdGC) resistant Gram-negative bacteria (GNB).

In addition, an ancillary study will be performed (only in participating centers from the Ile de France region) to compare :

The composition of the intestinal microbiota among patients with an early de-escalation guided by the betaLACTA® test results and a standard de-escalation on AST results at 48-72h.
The evolution of intestinal microbiota of patients after exposure to different beta-lactam antibiotics, from carbapenems or cefepim/ceftazidim during the empirical treatment, to the definitive beta-lactam antibiotic chosen to cure the infection after antibiotic susceptibility test results.
The outcomes of ICU patients (mortality at D90, occurrence of infection, ICU length of stay, etc.) according to the composition of their intestinal microbiota and to its evolution during antibiotic treatment.

To meet these objectives, 646 patients will be enrolled.

Conditions: Pneumonia, Urinary Tract Infections, Bloodstream Infection
Being tested: betaLACTA® rapid diagnostic test
Keywords: Carbapenems de-escalation, rapid diagnostic test,, Carbapenem-antimicrobial de-escalation-rapid diagnostic test
Medical subject headings: Pneumonia, Urinary Tract Infections, Sepsis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

betaLACTA® rapid diagnostic testDevice
Also called betaLACTA® test
Since ≥1 bacteriological sample(s) from ICU patients empirically treated with carbapenems (i.e. respiratory sample such as quantitative tracheobronchial aspirate with available volume ≥1 mL; urinary sample such as single catheter urine specimen; or blood culture) is positive for ≥2 GNB/field on direct examination, empirical carbapenem will be adapted: 1) early, since the second dose, according to the results of the betaLACTA® rapid diagnostic test (BLT) in the intervention arm (i.e. de-escalation to cefepim or to ceftazidim+amikacin in case of negativity, and carbapenem continuation in case of positivity); or 2) after 48-72h according to the results of the antibiotic susceptibility test in the control arm.

Study groups in NCT03147807
Study group	Role	What they receive
betaLACTA® result given to physician	Experimental	In the experimental group, betaLACTA® rapid diagnostic test guided de-escalation result will be given to physician at Day 0 and empirical carbapenems will be de-escalated to Cefepime or Ceftazidime +/- Amikacin since the second dose. Receives: Device: betaLACTA® rapid diagnostic test
betaLACTA® result NOT given to physician	No intervention	In the control group, betaLACTA® result will not be given to physician and patients will receive empirical carbapenem during the time required to obtain final results of antibiotic susceptibility test

What is being measured

The primary outcome is the main question the study is designed to answer.

mortality at D90 and infection recurrence during the ICU stay
Composite endpoint combining 90-day mortality and percentage of infection recurrence (same GNB on the same site of infection) during the ICU stay (within the limit of 90 days).
Recurrence will be defined a posteriori by 3 independent experts, blinded of the allocation group of patients in whom a suspected recurrence would have occurred, with predefined criteria.
Measured: Day 90

Secondary outcomes (7)

Exposure to carbapenems
- Number of days with carbapenem treatment after inclusion during ICU stay (within the limit of 28 days)
- Number of carbapenems Defined Daily Doses (DDD) after inclusion during ICU stay (within the limit of 28 days)
- Number of carbapenem-free and antibiotic free days at day 28 after inclusion
Measured: from Day 0, through ICU discharge or until 28 days after inclusion in case of prolonged ICU stay
Total use of ICU and hospital resources and cost-effectiveness of early de-escalation compared to standard de-escalation.
- ICU and hospital lengths of stay following randomization;
- Total cost and incremental cost-effectiveness ratio (cost per additional death/ infection averted).
Measured: from Day 0,throught hospital discharge or until 28 days after inclusion in case of prolonged ICU stay
Occurrence of other infections.
Percentage of new infections (same site of infection with other bacteria or other site of infection) during ICU stay (within the limit of 90 days).
Measured: From Day 0 to ICU discharge (within the limit of 90 days).
Colonization of the digestive tractus of patients with 3rd generation cephalosporins (3rdGC) resistant Gram-negative bacteria
New colonization of patients' digestive tractus with 3rdGC-resistant GNB (i.e. ESBL-producing Enterobacteriaceae, Carbapenemase-producing Enterobacteriaceae, high-concentration AmpC cephalosporinase-producing Enterobacteriaceae, multi-resistant non-fermenting GNB, etc.) will be assessed comparing the results of the culture on selective media of rectal swabs performed at inclusion and at D3, at the end of the antibiotic treatment, and at ICU discharge.
Characterization of acquired 3rdGC-resistant GNB and determination of their resistance mechanism(s) will be performed using standard microbiological processes and molecular biology.
Measured: From Day 0, through ICU discharge or until 28 days after inclusion in case of prolonged ICU stay
Composition of intestinal microbiota at Day 0
To compare the composition of intestinal microbiota among patients with an early de-escalation guided by the betaLACTA® test results and a standard de-escalation on antibiogram results at 48-72h.
Measured: from D0 to the end of the antimicrobial treatment of the infection leading to inclusion in the study, average 7-10 days
Composition of intestinal microbiota at day 3
To compare the evolution of intestinal microbiota of patients after exposure to different betalactam antibiotics, from carbapenems or cefepim/ceftazidim during the empirical treatment, to the definitive beta-lactam antibiotic chosen to cure the infection after antibiotic susceptibility test results.
Measured: from D0 to the end of the antimicrobial treatment of the infection leading to inclusion in the study, average 7-10 days
Composition of intestinal microbiota after antibiotic exposur
To compare the outcomes of ICU patients (mortality at Day 90, occurrence of infection, ICU length of stay, etc.) according to the composition of their intestinal microbiota and to its evolution during antibiotic treatment.
Measured: from D0 to the end of the antimicrobial treatment of the infection leading to inclusion in the study, average 7-10 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

20 Oct 201720 Oct 2019

First posted10 May 2017
Study start20 Oct 2017
Primary completion21 Sep 2019
Study completion20 Oct 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for PneumoniaStudies of the same condition, open and under way.
More trials run by Assistance Publique - Hôpitaux de ParisThe 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 N/A
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 75 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03147807
Sponsor's protocol ID: P 150940
Other IDs: N° IDRCB 2016-A00941-50
Acronym: BLUE-CarbA
Status last verified: Dec 2022
First submitted: 2 Feb 2017
Last updated: 19 Dec 2022
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Undecided

Publications

Garnier M, Gallah S, Vimont S, Benzerara Y, Labbe V, Constant AL, Siami S, Guerot E, Compain F, Mainardi JL, Montil M, Quesnel C; BLUE-CarbA study group.. Multicentre randomised controlled trial to investigate usefulness of the rapid diagnostic betaLACTA test performed directly on bacterial cell pellets from respiratory, urinary or blood samples for the early de-escalation of carbapenems in septic intensive care unit patients: the BLUE-CarbA protocol. BMJ Open. 2019 Feb 19;9(2):e024561. doi: 10.1136/bmjopen-2018-024561.
PubMed 30782909

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 19 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: BetaLACTA® Test-guided Early De-escalation of Empirical Carbapenems in Pulmonary, Urinary and Bloodstream Infections Diagnosed in Intensive Care Unit - BLUE¬-CarbA Study
ClinicalTrials.gov ID: NCT03147807
Acronym / sponsor ID: BLUE-CarbA / P 150940
Conditions: Pneumonia, Urinary Tract Infections, Bloodstream Infection
Keywords: Carbapenems de-escalation, rapid diagnostic test,, Carbapenem-antimicrobial de-escalation-rapid diagnostic test
Study type: Interventional
Recruitment status: Completed
Enrolment: 75 participants (actual)
Lead sponsor: Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
Study start: 20 Oct 2017 (actual)
Primary completion: 21 Sep 2019 (actual)
Study completion: 20 Oct 2019 (actual)
First posted: 10 May 2017 (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.

Experimental plan :

Randomized, open-labeled non-inferiority clinical trial involving an in vitro diagnostic medical device (close to a phase III study), comparing two parallel groups:

Experimental group: early carbapenems de-escalation since the second dose, guided by results of the betaLACTA® test performed directly on the bacterial pellet from the microbiological sample positive on direct examination.
Control group: carbapenems de-escalation guided by definitive results of the antibiotic susceptibility test obtained 48 to 72h after microbiological sampling (reference strategy).

Detailed description

This study is conducted on ICU patients with a suspected pneumonia, primary blood-stream infection (BSI), and/or urinary tract infection (UTI).

The secondary objectives are to compare the early de-escalation guided by the betaLACTA® test results to the reference strategy de-escalating on the AST results on:

The exposure to carbapenems.
The total use of ICU and hospital resources and the cost-effectiveness.
The occurrence of other infections.
The colonization of the digestive tractus of patients with 3rd generation cephalosporins (3rdGC) resistant Gram-negative bacteria (GNB).

In addition, an ancillary study will be performed (only in participating centers from the Ile de France region) to compare :

The composition of the intestinal microbiota among patients with an early de-escalation guided by the betaLACTA® test results and a standard de-escalation on AST results at 48-72h.
The evolution of intestinal microbiota of patients after exposure to different beta-lactam antibiotics, from carbapenems or cefepim/ceftazidim during the empirical treatment, to the definitive beta-lactam antibiotic chosen to cure the infection after antibiotic susceptibility test results.
The outcomes of ICU patients (mortality at D90, occurrence of infection, ICU length of stay, etc.) according to the composition of their intestinal microbiota and to its evolution during antibiotic treatment.

To meet these objectives, 646 patients will be enrolled.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
betaLACTA® result given to physician	Experimental	Device: betaLACTA® rapid diagnostic testIn the experimental group, betaLACTA® rapid diagnostic test guided de-escalation result will be given to physician at Day 0 and empirical carbapenems will be de-escalated to Cefepime or Ceftazidime +/- Amikacin since the second dose.
betaLACTA® result NOT given to physician	No intervention	–In the control group, betaLACTA® result will not be given to physician and patients will receive empirical carbapenem during the time required to obtain final results of antibiotic susceptibility test

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

ICU patients ≥18 years.
With a suspected pneumonia (according to CPIS definition), primary blood-stream infection (according to CDC definition), and/or urinary tract infection (according to IDSA Guidelines).
And presence of ≥2 GNB/field on direct examination of a respiratory sample (quantitative bronchial aspirate with an available volume ≥ 1mL), urinary sample or blood culture.
Leading to an empirical carbapenem prescription, not administered for more than 6 hours when considering the inclusion of the patient.
Written informed consent signed by the patient / the trustworthy person / the next-of-kin / close relative, or inclusion in case of emergency and written informed consent will been signed by the patient as soon as possible.

Key exclusion criteria (8 listed)

Pregnancy.
Allergy to beta-lactams.
Patients already treated with ongoing carbapenems for another documented infection, blocking carbapenem de-escalation.
Patients included in another interventional study.
Patients in whom a procedure of withdrawing life-sustaining treatment was decided before inclusion.

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
betaLACTA® rapid diagnostic testAlso: betaLACTA® testSince ≥1 bacteriological sample(s) from ICU patients empirically treated with carbapenems (i.e. respiratory sample such as quantitative tracheobronchial aspirate with available volume ≥1 mL; urinary sample such as single catheter urine specimen; or blood culture) is positive for ≥2 GNB/field on direct examination, empirical carbapenem will be adapted: 1) early, since the second dose, according to the results of the betaLACTA® rapid diagnostic test (BLT) in the intervention arm (i.e. de-escalation to cefepim or to ceftazidim+amikacin in case of negativity, and carbapenem continuation in case of positivity); or 2) after 48-72h according to the results of the antibiotic susceptibility test in the control arm.	Device	betaLACTA® result given to physician

Primary outcome

mortality at D90 and infection recurrence during the ICU stay
Time frame: Day 90
Composite endpoint combining 90-day mortality and percentage of infection recurrence (same GNB on the same site of infection) during the ICU stay (within the limit of 90 days). Recurrence will be defined a posteriori by 3 independent experts, blinded of the allocation group of patients in whom a suspected recurrence would have occurred, with predefined criteria.

7 secondary outcomes

Exposure to carbapenems
Time frame: from Day 0, through ICU discharge or until 28 days after inclusion in case of prolonged ICU stay
Total use of ICU and hospital resources and cost-effectiveness of early de-escalation compared to standard de-escalation.
Time frame: from Day 0,throught hospital discharge or until 28 days after inclusion in case of prolonged ICU stay
Occurrence of other infections.
Time frame: From Day 0 to ICU discharge (within the limit of 90 days).
Colonization of the digestive tractus of patients with 3rd generation cephalosporins (3rdGC) resistant Gram-negative bacteria
Time frame: From Day 0, through ICU discharge or until 28 days after inclusion in case of prolonged ICU stay
Composition of intestinal microbiota at Day 0
Time frame: from D0 to the end of the antimicrobial treatment of the infection leading to inclusion in the study, average 7-10 days
Composition of intestinal microbiota at day 3
Time frame: from D0 to the end of the antimicrobial treatment of the infection leading to inclusion in the study, average 7-10 days
Composition of intestinal microbiota after antibiotic exposur
Time frame: from D0 to the end of the antimicrobial treatment of the infection leading to inclusion in the study, average 7-10 days

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2022.
Derived from this study: PubMed 30782909Garnier M, Gallah S, Vimont S, Benzerara Y, Labbe V, Constant AL, Siami S, Guerot E, Compain F, Mainardi JL, Montil M, Quesnel C; BLUE-CarbA study group.. Multicentre randomised controlled trial to investigate usefulness of the rapid diagnostic betaLACTA test performed directly on bacterial cell pellets from respiratory, urinary or blood samples for the early de-escalation of carbapenems in septic intensive care unit patients: the BLUE-CarbA protocol. BMJ Open. 2019 Feb 19;9(2):e024561. doi: 10.1136/bmjopen-2018-024561.
Individual participant dataSharing planned: Undecided

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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.

Marc GARNIER, MD, PhD principal investigator

Assistance Publique - Hôpitaux de Paris

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing betaLACTA® rapid diagnostic test in people with Pneumonia and Urinary Tract Infections, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

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 6 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: finished, as of the sponsor's last update on 19 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

mortality at D90 and infection recurrence during the ICU stay (time frame: Day 90). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03147807, which also lists 1 linked publication.

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 19 Dec 2022.