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

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ClinicalTrials.gov Identifier: NCT02795949
Recruitment Status : Recruiting
First Posted : June 10, 2016
Last Update Posted : May 14, 2019
Sponsor:
Collaborator:
Spanish Network for Research in Infectious Diseases
Information provided by (Responsible Party):
Fundación Pública Andaluza para la gestión de la Investigación en Sevilla

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.


Condition or disease Intervention/treatment Phase
Enterobacteriaceae Infections Drug: Antipseudomonal beta-lactam antibiotic Drug: De-escalation(short-spectrum antibiotic) Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 344 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 2016
Estimated Primary Completion Date : January 2020
Estimated Study Completion Date : February 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Antibiotics

Arm Intervention/treatment
Experimental: Antipseudomonal beta-lactam antibiotic
  1. Ampicillin 2g IV/6h
  2. Trimethoprim/sulfamethoxazole 160/800 mg IV/8 -12h
  3. Cefuroxime 750-1000 mg IV/8h
  4. Cefotaxime 1-2g IV/8h ó ceftriaxone 1 g/12-24h
  5. Amoxicillin/clavulanate 1000/125 mg IV/8h
  6. Ciprofloxacin 400 mg IV/12h
  7. Ertapenem 1-2g/24h.
Drug: Antipseudomonal beta-lactam antibiotic
Pharmaceutical form: solution for infusion
Other Names:
  • Ampicillin
  • Trimethoprim/sulfamethoxazole
  • Cefuroxime
  • Amoxicillin/clavulanate
  • Ciprofloxacin
  • Ertapenem

Active Comparator: De-escalation(short-spectrum antibiotic)
  • Piperacillin/tazobactam 4/0.5 g IV/8h
  • Meropenem 1-2 g IV/8h
  • Imipenem 0.5 g IV/6h - 1g IV/6h
  • Aztreonam 1-2 g IV/8h
  • Ceftazidime 1-2 g IV/8h
  • Cefepime 2 g IV/8-12h
Drug: De-escalation(short-spectrum antibiotic)
Pharmaceutical form: solution for infusion
Other Names:
  • Piperacillin/tazobactam
  • Meropenem
  • Imipenem
  • Aztreonam
  • Ceftazidime
  • Cefepime




Primary Outcome Measures :
  1. Clinical cure at day 3-5 after treatment. [ Time Frame: Day 3-5 after end of treatment. ]
    Clinical cure: complete resolution of infection symptoms (bacteremia) present at the day on which the assessment is done and patient is alive.


Secondary Outcome Measures :
  1. Early clinical and microbiological response. [ Time Frame: After 5 days of treatment ]
    The infection was completely resolved after 5 days of treatment (patients without infection symptoms and a negative blood culture).

  2. Late clinical and microbiological response. [ Time Frame: Day 60 ]
    The infection was completely resolved at day 60 (patients without infection symptoms)

  3. Mortality [ Time Frame: At 7,14 and 30 days ]
    Death for any reason

  4. Length of hospital stay [ Time Frame: At 7,14 and 30 days ]
    Defined as the from admission to hospital discharge

  5. Recurrences (relapse or reinfection) rate [ Time Frame: Day 60 after treatment ]
  6. Safety of antibiotic treatment [ Time Frame: 60 days ]
    Gathering any related adverse event from the informed consent form signature up to 60 days

  7. Impact of the study treatment on intestinal microbiota [ Time Frame: Screening, Day 7-14, Day 12-21, Day 30 ]
    Effect of study treatment on colonization of the intestinal tract with multi drug resistant gram negative bacilli

  8. Treatment duration. [ Time Frame: It is not allowed treatment duration more than 28 days ]
    Evaluate the study treatment duration.

  9. Secondary infections. [ Time Frame: 60 days ]
    Evaluate the development of secondary infections other than the initial bacteremia.



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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02795949


Contacts
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Contact: Clara Rosso Fernández, MD, PhD 0034 955016414 claram.rosso.sspa@juntadeandalucia.es
Contact: Eva Recio, BS, PhD 600162652 eva.recio.exts@juntadeandalucia.es

Locations
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Spain
Jerez de la Frontera Hospital Recruiting
Jerez de la Frontera, Cádiz, Spain, 11138
Contact: Salvador Pérez Cortes, MD       salvador.perez.cortes.sspa@juntadeandalucia.es   
La Línea de La Concepción Hospital Terminated
La Línea de La Concepción, Cádiz, Spain
University Hospital Donostia Recruiting
San Sebastian, Gipúzcoa, Spain, 20080
Contact: Maialen Ibarguren Pinilla, MD       MAIALEN.IBARGURENPINILLA@osakidetza.eus   
Cruces Hospital Recruiting
Baracaldo, País Vasco, Spain
Contact: Josune Goikoetxea Agirre       ANEJOSUNE.GOIKOETXEAAGIRRE@osakidetza.net   
San Juan de Dios del Aljarafe Hospital Terminated
Bormujos, Sevilla, Spain, 41930
University General Hospital of Alicante Recruiting
Alicante, Spain, 03012
Contact: Esperanza Merino de Lucas, MD       merino_luc@gva.es   
University Hospital Mutua de Tarrasa Recruiting
Barcelona, Spain, 08221
Contact: Lucía Gómez García, MD       lgomez@mutuaterrassa.es   
University Hospital of Bellvitge Recruiting
Barcelona, Spain
Contact: Guillermo Cuervo Requena       guillermocuervo@hotmail.com   
University Hospital Puerta del Mar Recruiting
Cádiz, Spain, 11009
Contact: Francisca Guerrero Sánchez, MD, PhD       fcam.gs@gmail.com   
Puerto Real Hospital Recruiting
Cádiz, Spain
Contact: Patricia Jimenez, MD       patriciajaguilar@gmail.com   
La Coruña Hospital Recruiting
La Coruña, Spain
Contact: German Bou Arévalo       germanbou@canalejo.org   
Universitary Hospital of Leon Recruiting
León, Spain
Contact: Jose Manuel Guerra Laso       jmglaso@gmail.com   
University Hospital La Princesa Recruiting
Madrid, Spain, 28002
Contact: Ana Salas Aparicio, MD       asalasapa@yahoo.es   
University Hospital La Paz Recruiting
Madrid, Spain, 28046
Contact: Belen Loeches Yagüe, MD, Ms.C       bloeches@yahoo.es   
Universitary Hospital of Orense Recruiting
Orense, Spain
Contact: MªDolores Díaz Lòpez       Maria.Dolores.Diaz.Lopez@sergas.es   
Son Espases Hospital Recruiting
Palma de Mallorca, Spain, 07010
Contact: Mª Luisa Martín Pena, MD       lmartinpena@ssib.es   
University Clinic of Navarra Recruiting
Pamplona, Spain, 31008
Contact: José Ramón Yuste Ara, MD, PhD         
University Hospital Marqués de Valdecilla Recruiting
Santander, Spain, 30008
Contact: Mª Carmen Fariñas Álvarez, MD, PhD       mcfarinas@humv.es   
University Hospital Virgen Macarena Recruiting
Seville, Spain, 41071
Contact: Luis Eduardo López Cortés, MD, PhD       luiselopezcortes@gmail.com   
Universitary Hospital of Vigo Recruiting
Vigo, Spain
Contact: MªTeresa Pérez Rodriguez       maria.teresa.perez.rodriguez2@sergas.es   
University Hospital of Zaragoza Recruiting
Zaragoza, Spain, 28046
Contact: José Ramón Paño Pardo, MD, PhD       joserrapa@gmail.com   
Sponsors and Collaborators
Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
Spanish Network for Research in Infectious Diseases
Investigators
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Principal Investigator: Luis Eduardo Lopez Cortes, MD, PhD Universitary Hospital Virgen Macarena

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
ClinicalTrials.gov Identifier: NCT02795949     History of Changes
Other Study ID Numbers: SIMPLFY
First Posted: June 10, 2016    Key Record Dates
Last Update Posted: May 14, 2019
Last Verified: May 2019

Keywords provided by Fundación Pública Andaluza para la gestión de la Investigación en Sevilla:
Enterobacteriaceae
Bacteremia
Escalation
Bacterial resistance
Bloodstream infection
Recurrence

Additional relevant MeSH terms:
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Ampicillin
Bacteremia
Enterobacteriaceae Infections
Infection
Bacterial Infections
Sepsis
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Gram-Negative Bacterial Infections
Anti-Bacterial Agents
Amoxicillin
Ciprofloxacin
Meropenem
Tazobactam
Piperacillin
Clavulanic Acid
Clavulanic Acids
Imipenem
Ceftazidime
Ertapenem
Cefepime
Piperacillin, Tazobactam Drug Combination
Aztreonam
Lactams
Cefuroxime
beta-Lactams
Amoxicillin-Potassium Clavulanate Combination
Antibiotics, Antitubercular
Trimethoprim