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

NCT ID: NCT03147807

Last Updated: 2022-12-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

75 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-10-20

Study Completion Date

2019-10-20

Brief Summary

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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).

Detailed Description

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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

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Pneumonia Urinary Tract Infections Bloodstream Infection

Keywords

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Carbapenems de-escalation, rapid diagnostic test, Carbapenem-antimicrobial de-escalation-rapid diagnostic test

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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betaLACTA® result given to physician

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.

Group Type EXPERIMENTAL

betaLACTA® rapid diagnostic test

Intervention Type DEVICE

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.

betaLACTA® result NOT given to physician

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

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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betaLACTA® rapid diagnostic 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.

Intervention Type DEVICE

Other Intervention Names

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betaLACTA® test

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Marc GARNIER, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Locations

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Anesthesiology and Critical Care Medicine Department

Paris, , France

Site Status

Countries

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France

References

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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.

Reference Type DERIVED
PMID: 30782909 (View on PubMed)

Other Identifiers

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N° IDRCB 2016-A00941-50

Identifier Type: OTHER

Identifier Source: secondary_id

P 150940

Identifier Type: -

Identifier Source: org_study_id