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

NCT02795949 | Completed Phase 3

• 1 other identifier: SIMPLFY
• Study Type: interventional
• Target: 344
• Locations: 1 country
• Sites: 21

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.

Conditions

Enterobacteriaceae Infections

Keywords

Enterobacteriaceae; Bacteremia; Escalation; Bacterial resistance; Bloodstream infection; Recurrence

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• Early clinical and microbiological response.

  After 5 days of treatment

• Late clinical and microbiological response.

  Day 60

• Mortality

  At 7,14 and 30 days

• Length of hospital stay

  At 7,14 and 30 days

• Recurrences (relapse or reinfection) rate

  Day 60 after treatment

Study Arms (2)

Antipseudomonal beta-lactam antibiotic

EXPERIMENTAL

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

De-escalation(short-spectrum antibiotic)

ACTIVE COMPARATOR

* 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)

Interventions

Antipseudomonal beta-lactam antibiotic DRUG

Pharmaceutical form: solution for infusion

Also known as: Ampicillin, Trimethoprim/sulfamethoxazole, Cefuroxime, Amoxicillin/clavulanate, Ciprofloxacin, Ertapenem

Antipseudomonal beta-lactam antibiotic

De-escalation(short-spectrum antibiotic) DRUG

Pharmaceutical form: solution for infusion

Also known as: Piperacillin/tazobactam, Meropenem, Imipenem, Aztreonam, Ceftazidime, Cefepime

De-escalation(short-spectrum antibiotic)

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥18 years old hospitalized patients with bacteremia from any source with isolation of an enterobacteria in blood cultures.
• 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.
• Microorganism susceptible at least one treatment from the experimental arm.
• Patients with intravenous treatment at least 3 days from the randomization o 5 days from the initial blood culture.
• Patients to sign the informed consent form.

You may not qualify if:

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

Sponsors & Collaborators

• Fundación Pública Andaluza para la gestión de la Investigación en Sevilla: lead
• Spanish Network for Research in Infectious Diseases: collaborator

Study Sites (21)

Cruces Hospital

Barakaldo, Basque Country, Spain

Location

Jerez de la Frontera Hospital

Jerez de la Frontera, Cádiz, 11138, Spain

Location

La Línea de La Concepción Hospital

La Línea de la Concepción, Cádiz, Spain

Location

University Hospital Donostia

Donostia / San Sebastian, Gipúzcoa, 20080, Spain

Location

San Juan de Dios del Aljarafe Hospital

Bormujos, Sevilla, 41930, Spain

Location

La Coruña Hospital

A Coruña, Spain

Location

University General Hospital of Alicante

Alicante, 03012, Spain

Location

University Hospital Mutua de Tarrasa

Barcelona, 08221, Spain

Location

University Hospital of Bellvitge

Barcelona, Spain

Location

University Hospital Puerta del Mar

Cadiz, 11009, Spain

Location

Puerto Real Hospital

Cadiz, Spain

Location

Universitary Hospital of Leon

León, Spain

Location

University Hospital La Princesa

Madrid, 28002, Spain

Location

University Hospital La Paz

Madrid, 28046, Spain

Location

Universitary Hospital of Orense

Ourense, Spain

Location

Son Espases Hospital

Palma de Mallorca, 07010, Spain

Location

University Clinic of Navarra

Pamplona, 31008, Spain

Location

University Hospital Marqués de Valdecilla

Santander, 30008, Spain

Location

University Hospital Virgen Macarena

Seville, 41071, Spain

Location

Universitary Hospital of Vigo

Vigo, Spain

Location

University Hospital of Zaragoza

Zaragoza, 28046, Spain

Location

Related Publications (2)

• Lopez-Cortes LE, Delgado-Valverde M, Moreno-Mellado E, Goikoetxea Aguirre J, Guio Carrion L, Blanco Vidal MJ, Lopez Soria LM, Perez-Rodriguez MT, Martinez Lamas L, Arnaiz de Las Revillas F, Arminanzas C, Ruiz de Alegria-Puig C, Jimenez Aguilar P, Del Carmen Martinez-Rubio M, Saez-Bejar C, de Las Cuevas C, Martin-Aspas A, Galan F, Yuste JR, Leiva-Leon J, Bou G, Capon Gonzalez P, Boix-Palop L, Xercavins-Valls M, Goenaga-Sanchez MA, Anza DV, Caston JJ, Rufian MR, Merino E, Rodriguez JC, Loeches B, Cuervo G, Guerra Laso JM, Plata A, Perez Cortes S, Lopez Mato P, Sierra Monzon JL, Rosso-Fernandez C, Bravo-Ferrer JM, Retamar-Gentil P, Rodriguez-Bano J; SIMPLIFY study group. Efficacy and safety of a structured de-escalation from antipseudomonal beta-lactams in bloodstream infections due to Enterobacterales (SIMPLIFY): an open-label, multicentre, randomised trial. Lancet Infect Dis. 2024 Apr;24(4):375-385. doi: 10.1016/S1473-3099(23)00686-2. Epub 2024 Jan 9.

  PMID: 38215770 DERIVED

• 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.

  PMID: 28601833 DERIVED

Related Links

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

MeSH Terms

Conditions

Enterobacteriaceae Infections; Bacteremia; Sepsis; Recurrence

Interventions

Ampicillin; Trimethoprim, Sulfamethoxazole Drug Combination; Cefuroxime; Amoxicillin-Potassium Clavulanate Combination; Ciprofloxacin; Ertapenem; Piperacillin, Tazobactam Drug Combination; Meropenem; Imipenem; Aztreonam; Ceftazidime; Cefepime

Condition Hierarchy (Ancestors)

Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes

Intervention Hierarchy (Ancestors)

Penicillin G; Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Sulfamethoxazole; Benzenesulfonamides; Sulfonamides; Sulfanilamides; Aniline Compounds; Amines; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Trimethoprim; Pyrimidines; Heterocyclic Compounds, 1-Ring; Drug Combinations; Pharmaceutical Preparations; Cephalosporins; Thiazines; Clavulanic Acid; Clavulanic Acids; Amoxicillin; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Carbapenems; Tazobactam; Penicillanic Acid; Piperacillin; Thienamycins; Monobactams; Cephaloridine

Study Officials

• Luis Eduardo Lopez Cortes, MD, PhD

  Universitary Hospital Virgen Macarena

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 1, 2016
• First Posted: June 10, 2016
• Study Start: October 1, 2016
• Primary Completion: January 1, 2020
• Study Completion: January 1, 2020
• Last Updated: July 17, 2020

Record last verified: 2020-07

Locations

ES (21)