NCT02466438

Brief Summary

Severe infection is one of the main causes of disease in hospitalized children and can be deadly. With the lack of novel antibiotics approved in children and the emergence of drug resistant bacteria, there is a critical need to optimize dosing of existing antibiotics. Piperacillin-tazobactam is an antibiotic frequently used for treatment of severe infection in children in Canadian hospitals. To optimize this antibiotic's efficacy despite the rise of antibiotic resistance, alternative dosing strategy is commonly used in adults, which consists of prolonging the time during which the drug is infused (4 hours instead of 30 min). Children clear piperacillin-tazobactam from their bodies at a slower rate than adults, consequently extended-infusion strategy cannot be directly extrapolated from adult to children. We believe that younger children need piperacillin-tazobactam infusions that are shorter compared to adults to achieve appropriate concentrations.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
141

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Jan 2016

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 2, 2015

Completed
7 days until next milestone

First Posted

Study publicly available on registry

June 9, 2015

Completed
7 months until next milestone

Study Start

First participant enrolled

January 1, 2016

Completed
2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2018

Completed
Last Updated

April 19, 2018

Status Verified

April 1, 2018

Enrollment Period

2.9 years

First QC Date

June 2, 2015

Last Update Submit

April 18, 2018

Conditions

Keywords

AntibioticsPiperacillin-tazobactamResistant bacteria

Outcome Measures

Primary Outcomes (3)

  • Evaluation of Clearance (CL) for piperacillin and tazobactam

    Treatment days 1-14 followed by a safety observation period of 3 days after the last study dose.

    up to 14 days

  • Proportion of subjects who achieve Pharmacodynamic target (at least 50% of free plasma piperacillin concentration above the MIC [50% fT > MIC])

    Treatment days 1-14 followed by a safety observation period of 3 days after the last study dose.

    up to 14 days

  • Evaluation of Volume of distribution (V) for piperacillin and tazobactam

    Treatment days 1-14 followed by a safety observation period of 3 days after the last study dose.

    up to 14 days

Secondary Outcomes (1)

  • Proportion of subjects experiencing adverse events (AEs)

    up to 17 days

Study Arms (1)

Piperacillin-tazobactam

EXPERIMENTAL

Piperacillin-tazobactam administration (fixed combination, ratio piperacillin:tazobactam = 8:1). Recruitment stratified by age group and pediatric populations to ensure good representation of those subgroups. Maximum dose: 16g/day. Treatment duration: up to 14 days depending to the treating physician. Patients with Normal Renal function: * Pediatric and surgery units: 2-5 months (7); 6-11 months (7); 12-23 months (7); 2-6 years (16) * Pediatric intensive care unit (PICU): 2-5 months (7); 6-11 months (7); 12-23 months (7); 2-6 years (16) * Haematology-oncology unit: 2-5 months (7); 6-11 months (7); 12-23 months (7); 2-6 years (16) Patients with Acute Kidney injury: * Pediatric and surgery units: 2 months-6 years (10) * PICU: 2 months-6 years (10) * Haematology-oncology unit: 2 months-6 years (10)

Drug: Piperacillin-tazobactam

Interventions

* Normal renal function receiving new optimized piperacillin-tazobactam dosing regimen per age, dosing (mg/kg), duration of infusion * Age (2-5 months): 80 mg/kg/dose of medication every 8 hours for 4 hours * Age (≥6 months-6y): 130 mg/kg/dose of medication every 8 hours for 4 hours * Acute Kidney injury : Dosing as prescribed by treating physician

Also known as: Piperacillin-tazobactam combination product, Tazocin
Piperacillin-tazobactam

Eligibility Criteria

Age2 Months - 6 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • Children 2 months - 6 years of age\*
  • Piperacillin-tazobactam indicated per standard of care
  • Informed consent

You may not qualify if:

  • Insufficient venous access to allow extended infusion
  • History of anaphylaxis to β-lactams
  • Supported with extracorporeal membrane oxygenation (ECMO)
  • On renal replacement therapy
  • Cystic fibrosis
  • Acute Kidney injury
  • Chronic renal insufficiency defined as defined as a glomerular filtration rate of 10-60 mL/min/1.73 m2
  • Study population #2: Acute Kidney injury
  • Children 2 months - 6 years of age
  • Piperacillin-tazobactam indicated per standard of care
  • Informed consent
  • Acute Kidney injury defined as the following:
  • Doubling of serum creatinine according to upper limit of normal for age and gender or
  • Doubling of baseline serum creatinine (defined as the creatinine level at admission, if the value is within normal limit for age and gender) We wil use the smaller value of these 2 definitions to diagnose acute kidney injury in a given subject.
  • History of anaphylaxis to β-lactams
  • +4 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

St. Justine's Hospital

Montreal, Quebec, H3T 1C5, Canada

RECRUITING

MeSH Terms

Conditions

Infections

Interventions

Piperacillin, Tazobactam Drug Combination

Intervention Hierarchy (Ancestors)

TazobactamPenicillanic AcidPenicillinsbeta-LactamsLactamsAmidesOrganic ChemicalsPiperacillinAmpicillinPenicillin GSulfur CompoundsSulfonesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsDrug CombinationsPharmaceutical Preparations

Study Officials

  • Julie Autmizguine, MD, MHS

    St. Justine's Hospital

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD, MHS

Study Record Dates

First Submitted

June 2, 2015

First Posted

June 9, 2015

Study Start

January 1, 2016

Primary Completion

December 1, 2018

Study Completion

December 1, 2018

Last Updated

April 19, 2018

Record last verified: 2018-04

Locations