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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 : Completed
First Posted : June 10, 2016
Last Update Posted : July 17, 2020
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

Tracking Information
First Submitted Date  ICMJE April 1, 2016
First Posted Date  ICMJE June 10, 2016
Last Update Posted Date July 17, 2020
Actual Study Start Date  ICMJE October 2016
Actual Primary Completion Date January 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 8, 2018)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: June 6, 2016)
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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 8, 2018)
  • 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).
  • Late clinical and microbiological response. [ Time Frame: Day 60 ]
    The infection was completely resolved at day 60 (patients without infection symptoms)
  • Mortality [ Time Frame: At 7,14 and 30 days ]
    Death for any reason
  • Length of hospital stay [ Time Frame: At 7,14 and 30 days ]
    Defined as the from admission to hospital discharge
  • Recurrences (relapse or reinfection) rate [ Time Frame: Day 60 after treatment ]
  • Safety of antibiotic treatment [ Time Frame: 60 days ]
    Gathering any related adverse event from the informed consent form signature up to 60 days
  • 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
  • Treatment duration. [ Time Frame: It is not allowed treatment duration more than 28 days ]
    Evaluate the study treatment duration.
  • Secondary infections. [ Time Frame: 60 days ]
    Evaluate the development of secondary infections other than the initial bacteremia.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 6, 2016)
  • 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).
  • Late clinical and microbiological response. [ Time Frame: Day 60 ]
    The infection was completely resolved at day 60 (patients without infection symptoms)
  • Mortality [ Time Frame: At 7,14 and 30 days ]
    Death for any reason
  • Length of hospital stay [ Time Frame: At 7,14 and 30 days ]
    Defined as the from admission to hospital discharge
  • Recurrences (relapse or reinfection) rate [ Time Frame: Day 30 after treatment ]
  • Safety of antibiotic treatment [ Time Frame: 60 days ]
    Gathering any related adverse event from the informed consent form signature up to 60 days
  • 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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study on Reduced Antibiotic Treatment vs Broad Spectrum Betalactam in Patients With Bacteremia by Enterobacteriaceae
Official Title  ICMJE 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
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Enterobacteriaceae Infections
Intervention  ICMJE
  • Drug: Antipseudomonal beta-lactam antibiotic
    Pharmaceutical form: solution for infusion
    Other Names:
    • Ampicillin
    • Trimethoprim/sulfamethoxazole
    • Cefuroxime
    • Amoxicillin/clavulanate
    • Ciprofloxacin
    • Ertapenem
  • Drug: De-escalation(short-spectrum antibiotic)
    Pharmaceutical form: solution for infusion
    Other Names:
    • Piperacillin/tazobactam
    • Meropenem
    • Imipenem
    • Aztreonam
    • Ceftazidime
    • Cefepime
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Antipseudomonal beta-lactam antibiotic
  • 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
    Intervention: Drug: De-escalation(short-spectrum antibiotic)
Publications * López-Cortés LE, Rosso-Fernández C, Núñez-Núñez M, Lavín-Alconero L, Bravo-Ferrer J, Barriga Á, Delgado M, Lupión C, Retamar P, Rodríguez-Baño 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 6, 2016)
344
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE January 2020
Actual Primary Completion Date January 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 90 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02795949
Other Study ID Numbers  ICMJE SIMPLFY
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
Study Sponsor  ICMJE Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
Collaborators  ICMJE Spanish Network for Research in Infectious Diseases
Investigators  ICMJE
Principal Investigator: Luis Eduardo Lopez Cortes, MD, PhD Universitary Hospital Virgen Macarena
PRS Account Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP