Standard Vs Adjusted Dosing of Piperacillin/Tazobactam in Acute Renal Failure and Septic Shock
|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|
- 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 ]
- ICU and hospital mortality. ICU and hospital length of stay. Duration of mechanical ventilation. [ Time Frame: 1 months ] [ Designated as safety issue: No ]
|Study Start Date:||January 2009|
|Study Completion Date:||June 2011|
|Primary Completion Date:||May 2011 (Final data collection date for primary outcome measure)|
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
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
Piperacillin/Tazobactam 4.5g IV q 6h x 24 hours
Other Name: Tazocin
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00816790
|Canada, British Columbia|
|Royal Columbian Hospital|
|New Westminster, British Columbia, Canada, V3L 3W7|
|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|