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

NCT03891433 | Suspended Phase 4 DMC

• 1 other identifier: HUN-INF-CAPITIS-2018-1
• Study Type: interventional
• Target: 198
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Clinical cure.

  Complete resolution of non-bacteremic urinary tract infection signs or symptoms (dysuria, urinary frequency, urinary urgency, suprapubic pain or temperature greater than 38 degrees Celsius) present at trial entry (and no new signs or symptoms) until the duration of investigational antibacterial drug therapy. Investigators will compare the rate of clinical cure between the two treatment lines.

  At 5-7 day after the end of treatment (cure test), or for early response after 5 days from the start of treatment.

Secondary Outcomes (9)

• Microbiologic cure.

  At the 5-7 day after the end of treatment (cure test).

• Mortality in patient follow-up.

  Until day 30 after the first day of administration of the study drugs.

• Length of hospital stay in patient follow-up.

  Until day 30 after the first day of administration of the study drugs.

• Relapse.

  Daily until day 30 after the first day of administration of the study drugs.

• Reinfection.

  Daily until day 30 after the first day of administration of the study drugs.

Study Arms (2)

Carbapenems group

ACTIVE COMPARATOR

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.

Drug: Meropenem; Drug: Ertapenem 1000 MG

Piperacillin/tazobactam.

ACTIVE COMPARATOR

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

Drug: Piperacillin, Tazobactam 4-0.5G Solution for Injection

Interventions

Meropenem DRUG

Carbapenems group intervention.

Carbapenems group

Ertapenem 1000 MG DRUG

Carbapenems group intervention.

Carbapenems group

Piperacillin, Tazobactam 4-0.5G Solution for Injection DRUG

Piperacillin/Tazobactam group intervention.

Piperacillin/tazobactam.

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Universidad del Norte: lead

Study Sites (1)

Universidad del Norte´s Hospital

Soledad, Atlántico, 083001, Colombia

Location

Related Publications (6)

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

  PMID: 4386243 BACKGROUND

• 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.

  PMID: 18291338 BACKGROUND

• 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.

  PMID: 16223952 BACKGROUND

• 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.

  PMID: 28362938 BACKGROUND

• 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.

  PMID: 22057701 BACKGROUND

• 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.

  PMID: 30208454 BACKGROUND

MeSH Terms

Conditions

Urinary Tract Infections; Enterobacteriaceae Infections; Escherichia coli Infections

Interventions

Meropenem; Ertapenem; Piperacillin; Tazobactam; Solutions; Injections

Condition Hierarchy (Ancestors)

Infections; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses

Intervention Hierarchy (Ancestors)

Thienamycins; Carbapenems; beta-Lactams; Lactams; Amides; Organic Chemicals; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Ampicillin; Penicillin G; Penicillins; Sulfur Compounds; Penicillanic Acid; Sulfones; Pharmaceutical Preparations; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Diego F Viasus Perez, MD. PhD.

  Universidad del Norte´s Hospital-Infectious Diseases.

  PRINCIPAL INVESTIGATOR

• Andres F Estupinan Bohorquez, MD

  Universidad del Norte

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: 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).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2019
• First Posted: March 27, 2019
• Study Start: April 1, 2019
• Primary Completion: December 1, 2024
• Study Completion: April 1, 2026
• Last Updated: December 6, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

CO (1)