Study on Reduced Antibiotic Treatment vs Broad Spectrum Betalactam in Patients With Bacteremia by Enterobacteriaceae

Enterobacteriaceae Infections Clinical Trial

— SIMPLIFY  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02795949
• Other study ID #: SIMPLFY
• Status: Completed
• Phase: Phase 3
• Start date: October 2016
• Est. completion date: January 2020

Study information

• Verified date: July 2020
• Source: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 344
• Est. completion date: January 2020
• Est. primary completion date: January 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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 ß-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.

Related Conditions & MeSH terms

• Bacteremia
• Enterobacteriaceae Infections

Intervention

Drug:
• Antipseudomonal beta-lactam antibiotic
Pharmaceutical form: solution for infusion
• De-escalation(short-spectrum antibiotic)
Pharmaceutical form: solution for infusion

Locations

Country	Name	City	State
Spain	University General Hospital of Alicante	Alicante
Spain	Cruces Hospital	Baracaldo	País Vasco
Spain	University Hospital Mutua de Tarrasa	Barcelona
Spain	University Hospital of Bellvitge	Barcelona
Spain	San Juan de Dios del Aljarafe Hospital	Bormujos	Sevilla
Spain	Puerto Real Hospital	Cádiz
Spain	University Hospital Puerta del Mar	Cádiz
Spain	Jerez de la Frontera Hospital	Jerez de la Frontera	Cádiz
Spain	La Coruña Hospital	La Coruña
Spain	La Línea de La Concepción Hospital	La Línea de La Concepción	Cádiz
Spain	Universitary Hospital of Leon	León
Spain	University Hospital La Paz	Madrid
Spain	University Hospital La Princesa	Madrid
Spain	Universitary Hospital of Orense	Orense
Spain	Son Espases Hospital	Palma de Mallorca
Spain	University Clinic of Navarra	Pamplona
Spain	University Hospital Donostia	San Sebastian	Gipúzcoa
Spain	University Hospital Marqués de Valdecilla	Santander
Spain	University Hospital Virgen Macarena	Seville
Spain	Universitary Hospital of Vigo	Vigo
Spain	University Hospital of Zaragoza	Zaragoza

Sponsors (2)

Lead Sponsor	Collaborator
Fundación Pública Andaluza para la gestión de la Investigación en Sevilla	Spanish Network for Research in Infectious Diseases

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical cure at day 3-5 after treatment.	Clinical cure: complete resolution of infection symptoms (bacteremia) present at the day on which the assessment is done and patient is alive.	Day 3-5 after end of treatment.
Secondary	Early clinical and microbiological response.	The infection was completely resolved after 5 days of treatment (patients without infection symptoms and a negative blood culture).	After 5 days of treatment
Secondary	Late clinical and microbiological response.	The infection was completely resolved at day 60 (patients without infection symptoms)	Day 60
Secondary	Mortality	Death for any reason	At 7,14 and 30 days
Secondary	Length of hospital stay	Defined as the from admission to hospital discharge	At 7,14 and 30 days
Secondary	Recurrences (relapse or reinfection) rate		Day 60 after treatment
Secondary	Safety of antibiotic treatment	Gathering any related adverse event from the informed consent form signature up to 60 days	60 days
Secondary	Impact of the study treatment on intestinal microbiota	Effect of study treatment on colonization of the intestinal tract with multi drug resistant gram negative bacilli	Screening, Day 7-14, Day 12-21, Day 30
Secondary	Treatment duration.	Evaluate the study treatment duration.	It is not allowed treatment duration more than 28 days
Secondary	Secondary infections.	Evaluate the development of secondary infections other than the initial bacteremia.	60 days

External Links

•   Spanish Network for Research in Infectious Diseases (Red Española de Investigación en Patología Infecciosa)