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Enterobacteriaceae InfectionsPhase 3SIMPLIFYNCT02795949

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

A Phase 3 study testing Antipseudomonal beta-lactam antibiotic and De-escalation(short-spectrum antibiotic) in people with Enterobacteriaceae Infections, run by Fundación Pública Andaluza para la gestión de la Investigación en Sevilla at 21 sites in Spain.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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… Read more about this study

Who is it for?
Ages 18 to 90 years
Conditions the study is for
Enterobacteriaceae Infections
What is being tested?
Antipseudomonal beta-lactam antibiotic and De-escalation(short-spectrum antibiotic)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
344 participants
Where
21 sitesSpain
Study dates
Oct 2016to Jan 2020
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 90 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • ≥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.

Who cannot join

  • 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.

Trial locations and contacts

21 sites in 1 country.

21 sites in 1 country

Spain21 sites

  • La Coruña Hospital

    A Coruña

  • University General Hospital of Alicante

    Alicante, 03012

  • Cruces Hospital

    Barakaldo, Basque Country

  • University Hospital Mutua de Tarrasa

    Barcelona, 08221

  • University Hospital of Bellvitge

    Barcelona

  • San Juan de Dios del Aljarafe Hospital

    Bormujos, Sevilla, 41930

  • University Hospital Puerta del Mar

    Cadiz, 11009

  • Puerto Real Hospital

    Cadiz

  • University Hospital Donostia

    Donostia / San Sebastian, Gipúzcoa, 20080

  • Jerez de la Frontera Hospital

    Jerez de la Frontera, Cádiz, 11138

  • La Línea de La Concepción Hospital

    La Línea de la Concepción, Cádiz

  • Universitary Hospital of Leon

    León

  • University Hospital La Princesa

    Madrid, 28002

  • University Hospital La Paz

    Madrid, 28046

  • Universitary Hospital of Orense

    Ourense

  • Son Espases Hospital

    Palma de Mallorca, 07010

  • University Clinic of Navarra

    Pamplona, 31008

  • University Hospital Marqués de Valdecilla

    Santander, 30008

  • University Hospital Virgen Macarena

    Seville, 41071

  • Universitary Hospital of Vigo

    Vigo

  • University Hospital of Zaragoza

    Zaragoza, 28046

Other trials in Spain

About this study

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

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.

Being tested
Antipseudomonal beta-lactam antibiotic, De-escalation(short-spectrum antibiotic)
Keywords
Enterobacteriaceae, Bacteremia, Escalation, Bacterial resistance, Bloodstream infection, Recurrence
Medical subject headings
Enterobacteriaceae Infections, Bacteremia, Sepsis, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Antipseudomonal beta-lactam antibioticDrug

    Also called Ampicillin, Trimethoprim/sulfamethoxazole, Cefuroxime, Amoxicillin/clavulanate

    Pharmaceutical form: solution for infusion

  • De-escalation(short-spectrum antibiotic)Drug

    Also called Piperacillin/tazobactam, Meropenem, Imipenem, Aztreonam

    Pharmaceutical form: solution for infusion

Study groups in NCT02795949
Study groupRoleWhat they receive
Antipseudomonal beta-lactam antibioticExperimental1. 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.
Receives: 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
Receives: Drug: De-escalation(short-spectrum antibiotic)

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Day 3-5 after end of treatment.

Secondary outcomes (9)

  1. Early clinical and microbiological response.

    The infection was completely resolved after 5 days of treatment (patients without infection symptoms and a negative blood culture).

    Measured: After 5 days of treatment

  2. Late clinical and microbiological response.

    The infection was completely resolved at day 60 (patients without infection symptoms)

    Measured: Day 60

  3. Mortality

    Death for any reason

    Measured: At 7,14 and 30 days

  4. Length of hospital stay

    Defined as the from admission to hospital discharge

    Measured: At 7,14 and 30 days

  5. Recurrences (relapse or reinfection) rate

    Measured: Day 60 after treatment

  6. Safety of antibiotic treatment

    Gathering any related adverse event from the informed consent form signature up to 60 days

    Measured: 60 days

  7. 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

    Measured: Screening, Day 7-14, Day 12-21, Day 30

  8. Treatment duration.

    Evaluate the study treatment duration.

    Measured: It is not allowed treatment duration more than 28 days

  9. Secondary infections.

    Evaluate the development of secondary infections other than the initial bacteremia.

    Measured: 60 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Jun 2016 (estimated)
  2. Study startOct 2016
  3. Primary completionJan 2020
  4. Study completionJan 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
344 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02795949
Sponsor's protocol ID
SIMPLFY
Acronym
SIMPLIFY
Status last verified
Jul 2020
First submitted
1 Apr 2016
Last updated
17 Jul 2020
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 38215770

  • 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.

    PubMed 28601833

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Antipseudomonal beta-lactam antibiotic and De-escalation(short-spectrum antibiotic) in people with Enterobacteriaceae Infections, run by Fundación Pública Andaluza para la gestión de la Investigación en Sevilla at 21 sites in Spain.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 21 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Clinical cure at day 3-5 after treatment. (time frame: Day 3-5 after end of treatment.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02795949, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jul 2020.

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