Standard Vs Adjusted Dosing of Piperacillin/Tazobactam in Acute Renal Failure and Septic Shock

September 10, 2015 updated by: Sean Keenan, Fraser Health

A Comparison of Standard Vs Renal Dosing of Piperacillin/Tazobactam in Acute Renal Failure and Septic Shock

The objective of this study is to determine the feasibility of conducting a large scale randomized controlled trial comparing standard and renally adjusted dosage of antibiotics in the septic shock patients with acute renal dysfunction. We will use Piperacillin as the prototype antibiotic in our study.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Septic shock is a significant cause of morbidity and mortality. Early Goal Directed therapy, fluid resuscitation, use of vasopressors and/or inotropes, and appropriate empiric antibiotic administration remain the cornerstone of therapy in the treatment of septic shock. Despite aggressive interventions, the death rate from septic shock in North America remains as high as 50 percent.

Septic shock is defined as severe sepsis with hypotension not reversed by adequate fluid resuscitation. This state of distributive shock often results in hypo-perfusion of all major organ systems, including the kidneys, and is a common cause of multi-organ failure. Acute renal failure in the setting of septic shock often leads clinicians to adjust dosing of empiric antibiotics according to the apparent renal function. Renally adjusted antibiotic dosing in septic shock may be insufficient for several reasons. First, renal failure secondary to hypoperfusion often reverses following fluid resuscitation and vasopressor use, leading to subsequent under dosing. Second, a hypoperfusion state theoretically results in a reduction in the amount of antibiotic delivered to the site of infection. Lastly, for drugs with large volumes of distribution or prolonged half lives, large initial doses are required to quickly to achieve therapeutic concentrations.

To date, no studies have attempted to answer this important question by comparing standard doses to renally adjusted doses of empiric antibiotics in patients with both septic shock and renal dysfunction during the initial resuscitative period. Currently there is no uniform practice among clinicians with respect to antibiotic dosing, which reflects the paucity of evidence in this area. Some clinicians currently use full dosing of antibiotics in the setting of septic shock with acute renal failure while others adjust the dose based on renal function. Well designed, prospective, randomized controlled trials are urgently needed to clarify the role of antibiotic adjustment during the resuscitative period of septic shock.

The objective of this study is to determine the feasibility of conducting a large scale randomized controlled trial comparing standard and renally adjusted dosage of antibiotics in the septic shock patients with acute renal dysfunction. We will use Tazocin as the prototype antibiotic in our study.

Study Type

Interventional

Enrollment (Anticipated)

20

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • British Columbia
      • New Westminster, British Columbia, Canada, V3L 3W7
        • Royal Columbian Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

17 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients with septic shock according to the Surviving Sepsis Campaign
  • Age > 19
  • Most recent eGFR<40 mls/min

Exclusion Criteria:

  • Pregnant
  • Known chronic renal failure patients who are dialysis dependant
  • Administration of systemic antibiotics > 1 dose
  • Not expected to survive 28 days due to an underlying medical illness
  • Allergy to Piperacillin/Tazobactam or any components of formulation within

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Dose Adjusted
This arm will receive their broad spectrum antibiotic as an adjusted dose based on their renal function as measured when sepsis is diagnosed and antimicrobials are initiated
Drug: Piperacillin/Tazobactam
eGFR 20-40 mls/min: Piperacillin/Tazobactam 3.375g IV q6h x 24 hours eGFR < 20 mls/min: Piperacillin/Tazobactam 2.25g IV q6h x 24 hours
Other Names:
  • Tazocin
Drug: Piperacillin/Tazobactam
Piperacillin/Tazobactam 4.5g IV q 6h x 24 hours
Other Names:
  • Tazocin
Experimental: Unadjusted Dose
This arm will receive their broad spectrum antibiotic as an unadjusted dose regardless of their renal function
Drug: Piperacillin/Tazobactam
eGFR 20-40 mls/min: Piperacillin/Tazobactam 3.375g IV q6h x 24 hours eGFR < 20 mls/min: Piperacillin/Tazobactam 2.25g IV q6h x 24 hours
Other Names:
  • Tazocin
Drug: Piperacillin/Tazobactam
Piperacillin/Tazobactam 4.5g IV q 6h x 24 hours
Other Names:
  • Tazocin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
To determine rate of patient accrual (ability to identify and enrol patients in a timely fashion) and protocol adherence for this pilot randomized controlled trial.
Time Frame: 4 months
4 months

Secondary Outcome Measures

Outcome Measure
Time Frame
ICU and hospital mortality. ICU and hospital length of stay. Duration of mechanical ventilation.
Time Frame: 1 months
1 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fraser Health

Investigators

  • Principal Investigator: Sean Keenan, MD, Fraser Health Authority
  • Study Director: Matthew Wiens, BSc PharmD, Fraser Health Authority
  • Study Director: Vincent Mabasa, BSc PharmD, Fraser Health Authority
  • Study Director: Sanjiv Kangura, BSc, Fraser Health Authority

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2009

Primary Completion (Actual)

May 1, 2011

Study Completion (Actual)

June 1, 2011

Study Registration Dates

First Submitted

December 31, 2008

First Submitted That Met QC Criteria

December 31, 2008

First Posted (Estimate)

January 5, 2009

Study Record Updates

Last Update Posted (Estimate)

September 14, 2015

Last Update Submitted That Met QC Criteria

September 10, 2015

Last Verified

September 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FHREB 2008-085

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Septic Shock

Clinical Trials on Piperacillin/Tazobactam

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Ireland

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe