Clinical trial NCT02795949: Study on Reduced Antibiotic Treatment vs Broad Spectrum Betalactam in Patients With Bacteremia by Enterobacteriaceae
Official title: Randomized, Multicenter, Phase III, Controlled Clinical Trial, to Demonstrate the no Inferiority of Reduced Antibiotic Treatment vs a Broad Spectrum Betalactam Antipseudomonal Treatment in Patients With Bacteremia by Enterobacteriaceae
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Enterobacteriaceae Infections
Keywords: Enterobacteriaceae
Bacteremia
Escalation
Bacterial resistance
Bloodstream infection
Recurrence
Lead sponsor: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
Sponsor class: OTHER
Collaborators: name: Spanish Network for Research in Infectious Diseases
First posted: 2016-06-10
Enrollment: 344
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The continuous increase in the bacterial resistance rate and the slow arrival of new therapeutic options have turned into an antibiotic crisis. One of the strategies proposed by stewardship programs to try to change this situation described worldwide is the use of antibiotics with the lowest possible antimicrobial spectrum.

Enterobacteriaceae bacteremia is a good example of how this strategy would be applied. The empirical treatment of nosocomial bacteremia by Enterobacteriaceae comprises in several cases one or two antibiotics with antipseudomonal activity, being much less common than desirable a subsequent change to narrower spectrum antibiotics based on susceptibility data ("de escalation"). This is because the safety of de escalation is based only on expert advice and some observational studies, so their efficacy and safety is questioned by many clinicians and therefore its use is lower than desired. In fact, a recent systematic review of the Cochrane Library concluded that randomized studies to support this practice are needed. Investigators propose a "real clinical practice-based" randomized trial to compare the efficacy and safety of continuing with an antipseudomonal agents vs. de-escalation according to a pre-specified rule, in patients with bacteraemia due to Enterobacteriaceae.


Eligibility criteria: Inclusion Criteria:

1. ≥18 years old hospitalized patients with bacteremia from any source with isolation of an enterobacteria in blood cultures.
2. Active empiric treatment with antipseudomonal betalactamic at 48 hours from the symptoms of sepsis and the blood culture.The patient could have received any other type of antibiotic therapy up to 24 hours after blood extraction.
3. Microorganism susceptible at least one treatment from the experimental arm.
4. Patients with intravenous treatment at least 3 days from the randomization o 5 days from the initial blood culture.
5. Patients to sign the informed consent form.

Exclusion Criteria:

1. Palliative care or life expectance \< 90 days.
2. Pregnancy or lactation period.
3. To isolate the Extended-spectrum β-lactamases producing Enterobacteriaceae
4. Late randomization \>48 hours after the enterobacteriaceae blood culture´s identification
5. Severe neutropenic (\< 500 céls/mm3) at the randomization.
6. Treatment of infection \> 28 days (endocarditis and osteomyelitis) or meningitis.

Primary outcomes:
measure: Clinical cure at day 3-5 after treatment.
timeFrame: Day 3-5 after end of treatment.
Secondary outcomes:
measure: Early clinical and microbiological response.
timeFrame: After 5 days of treatment
measure: Late clinical and microbiological response.
timeFrame: Day 60
measure: Mortality
timeFrame: At 7,14 and 30 days
measure: Length of hospital stay
timeFrame: At 7,14 and 30 days
measure: Recurrences (relapse or reinfection) rate
timeFrame: Day 60 after treatment
measure: Safety of antibiotic treatment
timeFrame: 60 days
measure: Impact of the study treatment on intestinal microbiota
timeFrame: Screening, Day 7-14, Day 12-21, Day 30
measure: Treatment duration.
timeFrame: It is not allowed treatment duration more than 28 days
measure: Secondary infections.
timeFrame: 60 days
Other outcomes:
Locations:
city: Jerez de la Frontera
country: Spain
facility: Jerez de la Frontera Hospital
state: Cádiz
city: La Línea de La Concepción
country: Spain
facility: La Línea de La Concepción Hospital
state: Cádiz
city: San Sebastian
country: Spain
facility: University Hospital Donostia
state: Gipúzcoa
city: Baracaldo
country: Spain
facility: Cruces Hospital
state: País Vasco
city: Bormujos
country: Spain
facility: San Juan de Dios del Aljarafe Hospital
state: Sevilla
city: Alicante
country: Spain
facility: University General Hospital of Alicante
city: Barcelona
country: Spain
facility: University Hospital Mutua de Tarrasa
city: Barcelona
country: Spain
facility: University Hospital of Bellvitge
city: Cádiz
country: Spain
facility: University Hospital Puerta del Mar
city: Cádiz
country: Spain
facility: Puerto Real Hospital
city: La Coruña
country: Spain
facility: La Coruña Hospital
city: León
country: Spain
facility: Universitary Hospital of Leon
city: Madrid
country: Spain
facility: University Hospital La Princesa
city: Madrid
country: Spain
facility: University Hospital La Paz
city: Orense
country: Spain
facility: Universitary Hospital of Orense
city: Palma de Mallorca
country: Spain
facility: Son Espases Hospital
city: Pamplona
country: Spain
facility: University Clinic of Navarra
city: Santander
country: Spain
facility: University Hospital Marqués de Valdecilla
city: Seville
country: Spain
facility: University Hospital Virgen Macarena
city: Vigo
country: Spain
facility: Universitary Hospital of Vigo
city: Zaragoza
country: Spain
facility: University Hospital of Zaragoza
Study officials:
affiliation: Universitary Hospital Virgen Macarena
name: Luis Eduardo Lopez Cortes, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lopez-Cortes LE, Rosso-Fernandez C, Nunez-Nunez M, Lavin-Alconero L, Bravo-Ferrer J, Barriga A, Delgado M, Lupion C, Retamar P, Rodriguez-Bano J; SIMPLIFY Study Group. Targeted simplification versus antipseudomonal broad-spectrum beta-lactams in patients with bloodstream infections due to Enterobacteriaceae (SIMPLIFY): a study protocol for a multicentre, open-label, phase III randomised, controlled, non-inferiority clinical trial. BMJ Open. 2017 Jun 9;7(6):e015439. doi: 10.1136/bmjopen-2016-015439.