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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02795949
Recruitment Status : Completed
First Posted : June 10, 2016
Last Update Posted : July 17, 2020
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)
Actual 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
Actual Primary Completion Date : January 2020
Actual Study Completion Date : January 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.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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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

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 identifier (NCT number): NCT02795949

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Sponsors and Collaborators
Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
Spanish Network for Research in Infectious Diseases
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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 Identifier (NCT Number):
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Responsible Party: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla Identifier: NCT02795949    
Other Study ID Numbers: SIMPLFY
First Posted: June 10, 2016    Key Record Dates
Last Update Posted: July 17, 2020
Last Verified: July 2020
Keywords provided by Fundación Pública Andaluza para la gestión de la Investigación en Sevilla:
Bacterial resistance
Bloodstream infection
Additional relevant MeSH terms:
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Enterobacteriaceae Infections
Bacterial Infections
Systemic Inflammatory Response Syndrome
Pathologic Processes
Gram-Negative Bacterial Infections
Anti-Bacterial Agents
Clavulanic Acid
Piperacillin, Tazobactam Drug Combination
Amoxicillin-Potassium Clavulanate Combination
Antibiotics, Antitubercular