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

This study has suspended participant recruitment.
(Study stopped because of study personel movement to another institution.)
Sponsor:
Information provided by:
Fraser Health
ClinicalTrials.gov Identifier:
NCT00816790
First received: December 31, 2008
Last updated: June 30, 2010
Last verified: October 2009
  Purpose

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.


Condition Intervention Phase
Septic Shock
Acute Renal Failure
Drug: Piperacillin/Tazobactam
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Treatment
Official Title: A Comparison of Standard Vs Renal Dosing of Piperacillin/Tazobactam in Acute Renal Failure and Septic Shock

Resource links provided by NLM:


Further study details as provided by Fraser Health:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • ICU and hospital mortality. ICU and hospital length of stay. Duration of mechanical ventilation. [ Time Frame: 1 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: January 2009
Estimated Study Completion Date: June 2011
Estimated Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Tazocin
Experimental: Unadjusted Dose
This arm will receive their broad spectrum antibiotic as an unadjusted dose regardless of their renal function
Drug: Piperacillin/Tazobactam
Piperacillin/Tazobactam 4.5g IV q 6h x 24 hours
Other Name: Tazocin

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.

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00816790

Locations
Canada, British Columbia
Royal Columbian Hospital
New Westminster, British Columbia, Canada, V3L 3W7
Sponsors and Collaborators
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
  More Information

No publications provided

Responsible Party: Dr Sean Keenan, MD, FRCPC, Department of Critical Care Medicine, Royal Columbian Hospital
ClinicalTrials.gov Identifier: NCT00816790     History of Changes
Other Study ID Numbers: FHREB 2008-085
Study First Received: December 31, 2008
Last Updated: June 30, 2010
Health Authority: Canada: Ethics Review Committee

Keywords provided by Fraser Health:
Septic shock
Acute Renal Failure
Antimicrobial
Drug Dosing
Feasibility Study

Additional relevant MeSH terms:
Acute Kidney Injury
Renal Insufficiency
Shock
Shock, Septic
Infection
Inflammation
Kidney Diseases
Pathologic Processes
Sepsis
Systemic Inflammatory Response Syndrome
Urologic Diseases
Penicillanic Acid
Piperacillin
Piperacillin-tazobactam combination product
Tazobactam
Anti-Bacterial Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014