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

NCT ID: NCT00816790

Last Updated: 2015-09-14

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-01-31
• Study Completion Date: 2011-06-30

Brief 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.

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.

Conditions

Septic Shock; Acute Renal Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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

Group Type: ACTIVE_COMPARATOR

Piperacillin/Tazobactam

Intervention Type: DRUG

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

Unadjusted Dose

This arm will receive their broad spectrum antibiotic as an unadjusted dose regardless of their renal function

Group Type: EXPERIMENTAL

Piperacillin/Tazobactam

Intervention Type: DRUG

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

Interventions

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

Intervention Type: DRUG

Piperacillin/Tazobactam

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

Intervention Type: DRUG

Other Intervention Names

Tazocin; Tazocin

Eligibility 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

• Minimum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fraser Health

OTHER

Sponsor Role: lead

Responsible Party

Sean Keenan

Intensivist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sean Keenan, MD

Role: PRINCIPAL_INVESTIGATOR

Fraser Health Authority

Matthew Wiens, BSc PharmD

Role: STUDY_DIRECTOR

Fraser Health Authority

Vincent Mabasa, BSc PharmD

Role: STUDY_DIRECTOR

Fraser Health Authority

Sanjiv Kangura, BSc

Role: STUDY_DIRECTOR

Fraser Health Authority

Locations

Royal Columbian Hospital

New Westminster, British Columbia, Canada

Countries

Canada

Other Identifiers

FHREB 2008-085

Identifier Type: -

Identifier Source: org_study_id