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

NCT03147807 | Completed

• 2 other identifiers: P 150940N° IDRCB 2016-A00941-50
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Pneumonia; Urinary Tract Infections; Bloodstream Infection

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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.

  Day 90

Secondary Outcomes (7)

• Exposure to carbapenems

  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.

  from Day 0,throught hospital discharge or until 28 days after inclusion in case of prolonged ICU stay

• Occurrence of other infections.

  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

  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

  from D0 to the end of the antimicrobial treatment of the infection leading to inclusion in the study, average 7-10 days

Study Arms (2)

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.

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

Interventions

betaLACTA® rapid diagnostic test 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.

Also known as: betaLACTA® test

betaLACTA® result given to physician

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Patients affiliated to French social security.

You may not qualify if:

• 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.
• Moribund patients.
• Patients with aplasia.
• Patients under tutorship/curatorship or patient deprived of freedom

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Anesthesiology and Critical Care Medicine Department

Paris, 75020, France

Location

Related Publications (1)

• 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.

  PMID: 30782909 DERIVED

MeSH Terms

Conditions

Pneumonia; Urinary Tract Infections; Sepsis

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Lung Diseases; Respiratory Tract Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Marc GARNIER, MD, PhD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 2, 2017
• First Posted: May 10, 2017
• Study Start: October 20, 2017
• Primary Completion: September 21, 2019
• Study Completion: October 20, 2019
• Last Updated: December 19, 2022

Record last verified: 2022-12

Locations

FR (1)