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

Septic Shock Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00816790
• Other study ID #: FHREB 2008-085
• Status: Terminated
• Phase: Phase 4
• First received: December 31, 2008
• Last updated: September 10, 2015
• Start date: January 2009
• Est. completion date: June 2011

Study information

• Verified date: September 2015
• Source: Fraser Health
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Ethics Review Committee
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 20
• Est. completion date: June 2011
• Est. primary completion date: May 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 19 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Kidney Injury
• Acute Renal Failure
• Renal Insufficiency
• Septic Shock
• Shock
• Shock, Septic

Intervention

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
• Piperacillin/Tazobactam
Piperacillin/Tazobactam 4.5g IV q 6h x 24 hours

Locations

Country	Name	City	State
Canada	Royal Columbian Hospital	New Westminster	British Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Fraser Health

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		4 months	No
Secondary	ICU and hospital mortality. ICU and hospital length of stay. Duration of mechanical ventilation.		1 months	No