Piperacillin/Tazobactam Versus Carbapenems in Non-bacteremic UTI Due to -ESBL-producing Enterobacteriaceae

NCT ID: NCT03891433

Last Updated: 2024-12-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

SUSPENDED

Clinical Phase

PHASE4

Total Enrollment

198 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-04-01

Study Completion Date

2026-04-01

Brief Summary

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This study evaluates the efficacy in achieving clinical cure in non-bacteremic urinary tract infections (UTI) caused by Escherichia coli or Klebsiella pneumoniae producers of extended-spectrum β-lactamases (ESBL) in adult patients. Half of participants will receive Piperacillin/Tazobactam as treatment, while the other half will receive Carbapenems.

The investigators will verify that Piperacillin/Tazobactam is not inferior in achieving clinical cure, and that is not associated with a higher risk of adverse events in the directed treatment of non-bacteremic UTI compared to Carbapenems.

The researchers hope to improve the use of antibiotics in the non-bacteremic UTI, reducing the "collateral damage" related to a deterioration in the prognosis of patients and the generation of resistant germs caused by the use of broad-spectrum antibiotics as carbapenems.

Detailed Description

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Urinary tract infection (UTI) is a common cause of hospitalization worldwide, the prevalence throughout the life of UTI has been reported in about 50,000 cases per 100,000 women and 13,000 per 100,000 men in the United States. Hospitalization for community-acquired UTI is about 33%. Furthermore, the UTI related to bladder catheterization during hospitalization is the most common type of infection acquired, representing 40% of all nosocomial infections. UTI hospitalization is associated with a high cost to the healthcare system.

The diagnosis of UTI is based on demonstrating the presence of bacteria urine in patients with suggestive clinical manifestations and verifying the host's inflammatory response to infection. The most common etiological agents include Escherichia coli, Klebsiella spp, and Proteus spp, with different prevalence and antibiotic susceptibility profiles among different populations.

Currently the appropriate treatment of UTI is a growing concern in the medical community because Gram-negative, specifically Enterobacteriaceae, bacteria have acquired genes encoding antibiotic resistance mechanisms. The β-lactamase spread spectrum (ESBL) are documented with increasing frequency among microorganisms causing UTI. Current treatment options for ESBL bacteria include nitrofurantoin, fosfomycin, piperacillin-tazobactam, carbapenems, and aminoglycosides.

Carbapenems and piperacillin-tazobactam are antibiotics used in medical practice for many years, both therapies are licensed for the treatment of non-bacteremic UTI; however, so far there is not enough evidence to discriminate the best choice for the treatment of non-bacteremic UTI (although carbapenems are considered drugs of choice for infections caused by these microorganisms), but carbapenems use has been associated with an increased risk of "collateral damage" related to the generation of resistant germs.

The investigators will compare between piperacillin/tazobactam and carbapenems the effectiveness in achieving clinical cure for non-bacteremic UTI caused by ESBL microorganisms. Researchers principal hypothesis is that Piperacillin/tazobactam is not inferior to carbapenems in achieving clinical cure in the targeted treatment of UTI caused by non-bacteremic due to E. coli or K. pneumoniae ESBL in adults requiring hospitalization. Researchers will verify too if Piperacillin/Tazobactam is not associated with increased risk of adverse events during the targeted treatment of non-bacteremic ITU caused by E. coli or K. pneumoniae ESBL in adults requiring hospital admission, compared with Carbapenems therapy.

To perform the protocol researchers follows the recommendations for the design of trials investigating treatment options for resistant bacteria multidrug (Uncomplicated Urinary Tract Infections: Developing Drugs for Treatment) of the United States Agency for Food and Drug Administration (FDA).

Participants will be included in the study with informed consent. The study variables will be obtained by patient interview and review of medical history. Variables will be recorded in a computerized database developed specifically for this study, with exclusive access for the researchers.

The estimated project duration is 2 years expected to begin in april of 2019.

Conditions

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Urinary Tract Infections Enterobacteriaceae Infections Infection Due to ESBL Bacteria Carbapenem Escherichia Coli Infection Klebsiella Pneumoniae Infection Clinical Trial Drug Resistance, Bacterial

Keywords

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adult Equivalence Trial Randomized Controlled Trial Comparative Study Anti-Bacterial Agents/therapeutic use* Meropenem Ertapenem Piperacillin, Tazobactam Drug Combination Escherichia coli Infections/drug therapy Klebsiella Infections/drug therapy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors
An investigator of the research project conducted daily monitoring of the patient and will not be involved in clinical decisions. The statistical analyzes performed finally be blind to the treatment received by the patients (carbapenems vs piperacillin/tazobactam).

Study Groups

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Carbapenems group

Meropenem (1g intravenously every 8 hours or adjusted to renal function) or Ertapenem (1g intravenously every 24 hours or adjusted to renal function) by 10 days.

Group Type ACTIVE_COMPARATOR

Meropenem

Intervention Type DRUG

Carbapenems group intervention.

Ertapenem 1000 MG

Intervention Type DRUG

Carbapenems group intervention.

Piperacillin/tazobactam.

Piperacillin / Tazobactam (4.5gr intravenously every 6 hours or adjusted to renal function) by 10 days.

Group Type ACTIVE_COMPARATOR

Piperacillin, Tazobactam 4-0.5G Solution for Injection

Intervention Type DRUG

Piperacillin/Tazobactam group intervention.

Interventions

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Meropenem

Carbapenems group intervention.

Intervention Type DRUG

Ertapenem 1000 MG

Carbapenems group intervention.

Intervention Type DRUG

Piperacillin, Tazobactam 4-0.5G Solution for Injection

Piperacillin/Tazobactam group intervention.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Adults (≥18 years) with hospital admission for non-bacteremic UTI caused by E. coli or K. pneumoniae ESBL susceptible to piperacillin/tazobactam and carbapenems.
* Presence of any risk factor associated with UTI due to ESBL germs: older age 64 years, diabetes mellitus, bladder catheter, previous antibiotics in the last 6 months, hospitalization in the last 6 months, urological surgery in the last 30 days, infections recurrent urinary.
* Diagnosis of UTI confirmed by: 1) fever, 2) urine culture\> 100000 CFU with isolation E. coli or K. pneumoniae ESBL susceptible to piperacillin / tazobactam and carbapenems, and 3) lumbar and / or abdominal pain with or without low urinary symptoms (dysuria, tenesmus, urgency), and 4) no other cause that explains the patient's symptoms
* Signed informed consent.
* Negative pregnancy test in fertile women.

Exclusion Criteria

* Non-acceptance of participation in the study.
* Pregnancy.
* Hypersensitivity and/or previous intolerance to penicillins, piperacillin/tazobactam or carbapenems.
* Bacteremia, hematogenous infection or other concomitant infection.
* Immunosuppression.
* In case of obstructive uropathy, lack of early surgical resolution.
* Evidence of acute or chronic prostatitis.
* Renal abscess
* Polycystic disease in the kidneys.
* Palliative care or life expectancy \<90 days.
* Heart failure (NYHA) functional class III or IV.
* Liver cirrhosis.
* Renal insufficiency in dialysis treatment.
* Empirical active treatment against bacteria isolated by urine cultures other than E. coli or K. pneumoniae BLEE.
* Participation in another clinical trial for infections.
* Hypersensitivity to amide-type local anesthetics.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Universidad del Norte

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Diego F Viasus Perez, MD. PhD.

Role: PRINCIPAL_INVESTIGATOR

Universidad del Norte´s Hospital-Infectious Diseases.

Andres F Estupinan Bohorquez, MD

Role: PRINCIPAL_INVESTIGATOR

Universidad del Norte

Locations

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Universidad del Norte´s Hospital

Soledad, Atlántico, Colombia

Site Status

Countries

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Colombia

References

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Hwang K. Semiquinone of D-amino acid oxidase. Med J Osaka Univ. 1967 Dec;18(3):175-84. No abstract available.

Reference Type BACKGROUND
PMID: 4386243 (View on PubMed)

Pitout JD, Laupland KB. Extended-spectrum beta-lactamase-producing Enterobacteriaceae: an emerging public-health concern. Lancet Infect Dis. 2008 Mar;8(3):159-66. doi: 10.1016/S1473-3099(08)70041-0.

Reference Type BACKGROUND
PMID: 18291338 (View on PubMed)

Paterson DL, Bonomo RA. Extended-spectrum beta-lactamases: a clinical update. Clin Microbiol Rev. 2005 Oct;18(4):657-86. doi: 10.1128/CMR.18.4.657-686.2005.

Reference Type BACKGROUND
PMID: 16223952 (View on PubMed)

Tamma PD, Rodriguez-Bano J. The Use of Noncarbapenem beta-Lactams for the Treatment of Extended-Spectrum beta-Lactamase Infections. Clin Infect Dis. 2017 Apr 1;64(7):972-980. doi: 10.1093/cid/cix034.

Reference Type BACKGROUND
PMID: 28362938 (View on PubMed)

Rodriguez-Bano J, Navarro MD, Retamar P, Picon E, Pascual A; Extended-Spectrum Beta-Lactamases-Red Espanola de Investigacion en Patologia Infecciosa/Grupo de Estudio de Infeccion Hospitalaria Group. beta-Lactam/beta-lactam inhibitor combinations for the treatment of bacteremia due to extended-spectrum beta-lactamase-producing Escherichia coli: a post hoc analysis of prospective cohorts. Clin Infect Dis. 2012 Jan 15;54(2):167-74. doi: 10.1093/cid/cir790. Epub 2011 Nov 4.

Reference Type BACKGROUND
PMID: 22057701 (View on PubMed)

Harris PNA, Tambyah PA, Lye DC, Mo Y, Lee TH, Yilmaz M, Alenazi TH, Arabi Y, Falcone M, Bassetti M, Righi E, Rogers BA, Kanj S, Bhally H, Iredell J, Mendelson M, Boyles TH, Looke D, Miyakis S, Walls G, Al Khamis M, Zikri A, Crowe A, Ingram P, Daneman N, Griffin P, Athan E, Lorenc P, Baker P, Roberts L, Beatson SA, Peleg AY, Harris-Brown T, Paterson DL; MERINO Trial Investigators and the Australasian Society for Infectious Disease Clinical Research Network (ASID-CRN). Effect of Piperacillin-Tazobactam vs Meropenem on 30-Day Mortality for Patients With E coli or Klebsiella pneumoniae Bloodstream Infection and Ceftriaxone Resistance: A Randomized Clinical Trial. JAMA. 2018 Sep 11;320(10):984-994. doi: 10.1001/jama.2018.12163.

Reference Type BACKGROUND
PMID: 30208454 (View on PubMed)

Other Identifiers

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HUN-INF-CAPITIS-2018-1

Identifier Type: -

Identifier Source: org_study_id