Tumescent Antibiotic Delivery Pharmacokinetics
Primary Purpose
Prevention of Surgical Site Infections
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Tumescent Antibiotic Delivery of cefazolin with or without metronidazole
Intravenous Antibiotic Delivery
Sponsored by
About this trial
This is an interventional prevention trial for Prevention of Surgical Site Infections focused on measuring Surgical site infections, Prevention, Prophylaxis, Tumescent, Intravenous, Antibiotic, Absorption, Pharmacokinetics, Bioavailability
Eligibility Criteria
Inclusion Criteria:
- Healthy adult
- No allergies to cefazolin, metronidazole or lidocaine
Exclusion Criteria:
- HIV
- Hepatitis C
- Diabetes
Sites / Locations
- Capistrano Surgery Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Tumescent Antibiotic Delivery
Intravenous Antibiotic Delivery
Arm Description
TAD followed by sequential serum and interstitial tissue fluid sampling for antibiotic concentration of subsequent 24 hours
Intravenous antibiotic delivery of cefazolin with or without metronidazole followed by sequential serum and interstitial tissue fluid sampling for antibiotic concentration of subsequent 24 hours.
Outcomes
Primary Outcome Measures
Area Under the Curve (AUC) of antibiotic concentration as a function of time
Secondary Outcome Measures
Full Information
NCT ID
NCT01046981
First Posted
January 11, 2010
Last Updated
September 27, 2011
Sponsor
Klein, Jeffrey A., M.D.
1. Study Identification
Unique Protocol Identification Number
NCT01046981
Brief Title
Tumescent Antibiotic Delivery Pharmacokinetics
Official Title
Tumescent Antibiotic Delivery: Pharmacokinetic Evidence for Improved Surgical Site Infection Prevention
Study Type
Interventional
2. Study Status
Record Verification Date
September 2011
Overall Recruitment Status
Completed
Study Start Date
March 2009 (undefined)
Primary Completion Date
April 2011 (Actual)
Study Completion Date
August 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Klein, Jeffrey A., M.D.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Tumescent Antibiotic Delivery (TAD) is a technique for improving the prevention of surgical site infections (SSI). TAD involves the subcutaneous infiltration of tumescent local anesthesia (TLA) containing water soluble antibiotic(s) such as cefazolin and metronidazole. TLA consists of the subcutaneous infiltration of very dilute lidocaine (≤ 1 gram/liter) and epinephrine (≤ 1 milligram/liter) with sodium bicarbonate (10 milliequivalents/liter) in a physiologic solution of sodium chloride which produces intense local anesthesia associated with profound wide-spread vasoconstriction lasting for more than 12 hours. Compared to intravenous antibiotic delivery (IVAD), TAD is expected to produce higher local tissue concentrations of the antibiotic(s) for longer periods of time and lower systemic/serum antibiotic concentrations. This clinical trial will compare TAD to IVAD with respect to pharmacokinetic evidence for possible improved SSI prevention.
Detailed Description
The protocol entitled Absorption Kinetics of Subcutaneous Tumescent Cefazolin and Metronidazole is a Phase I dose ranging clinical study designed to document the concentration-time profile of cefazolin and lidocaine after subcutaneous infiltration of cefazolin in tumescent local anesthesia (TLA). The antibiotic cefazolin is routinely given intravenously (IV) for the prophylaxis of surgical site infections (SSI).
Tumescent local anesthesia (TLA) consists of the subcutaneous infiltration of very dilute lidocaine (≤ 1 gram/liter) and epinephrine (≤ 1 milligram/liter) with sodium bicarbonate (10 milliequivalents/liter) in a physiologic solution of sodium chloride. Clinically TLA produces intense local anesthesia associated with profound wide-spread vasoconstriction lasting for more than 12 hours. Tumescent delivery of a cefazolin refers to the subcutaneous infiltration of cefazolin dissolved in a dilute solution of tumescent local anesthesia.
For a number of surgical procedures the current standard of care for prophylaxis of surgical site infection (SSI) is IV antibiotics (e.g. cefazolin) administered within 30 to 60 minutes before a surgical incision. We hypothesize that tumescent delivery of cefazolin may be more effective in preventing SSI and possibly safer with fewer side effects compared to IV delivery of cefazolin.
This protocol is a preliminary step in exploring the possibility that tumescent delivery of cefazolin is better than standard IV delivery for the prevention of SSI. The present protocol is a phase I study that will document and compare serum and tissue cefazolin levels after IV and subcutaneous tumescent delivery. A finding that tumescent delivery provides prolonged tissue levels of cefazolin will justify a phase II study of tumescent cefazolin at the site of an anticipated surgical incision for SSI prevention.
• Summary of Experimental Design of Clinical Trial Protocol The tumescent cefazolin study protocol is organized as follows. The tumescent cefazolin clinical study protocol will involve four adult volunteer subjects/participants. Each subject will participate in up to four (4) separate 12 to 24-hour investigative procedures at least one to two weeks apart. Concentrations of drugs in the solution of tumescent local anesthesia will be: lidocaine ≤ 1000 mg/L, epinephrine ≤ 1.0 mg/L, sodium bicarbonate 10 meq/L, cefazolin ≤ 1 gm/L with or without metronidazole 500mg/L . Maximum total cefazolin dose will be 1 gm. The maximum total metronidazole dose will be 500 mg. The maximum tumescent lidocaine dosage will be 20 mg/kg. TLA will be delivered into subcutaneous fat by peristaltic infiltration pump using blunt-tipped infiltration cannulas.
Procedures 1 & 2: Subcutaneous infiltration of tumescent cefazolin: Two of the four investigative procedures will begin with infiltration of a solution of tumescent local anesthesia containing cefazolin. Following infiltration of subcutaneous tumescent local anesthesia containing cefazolin approximately 9 sequential blood and tissue samples are taken over 12 to 24 hours. In these two studies a minimal volume of liposuction (10 ml to 12 ml using a hand held syringe) will be done in order to obtain samples of subcutaneous fat and tumescent subcutaneous interstitial tissue-fluid for measurement of cefazolin and metronidazole concentration.
Procedure 3: IV infusion of cefazolin or metronidazole: In the control study the patient is given 1 gm of IV cefazolin with or without 500 mg of metronidazole and subsequent sequential serum samples for antibiotic concentration will be obtained over 12 hours.
Serum Samples: Sequential sampling of serum and fat will be obtained at 0, 1, 3, 6, 9, 12, 18, and 24 hour (T0, T1, T3, T6, T9, T12, T15, T18 and T24), where T0 = time of completion of tumescent infiltration or IV infusion. Serum samples will be obtained from a peripheral vein via an indwelling catheter and analyzed for cefazolin concentration by HPLC.
Tissue Fluid Samples: Samples of subcutaneous tissue fluid will be obtained by liposuction of approximately 10 ml of subcutaneous fat and tumescent anesthetic solution using a hand-held syringe, the aspirate being centrifuged to obtain an aqueous infranate from which cefazolin, metronidazole and lidocaine concentration will be measured by HPLC. Clinical experience has shown that tumescent local anesthesia persists for at least 12 hours. If the patient experiences any significant discomfort during the aspiration of subcutaneous fat using a hand-held syringe, then no further subcutaneous tissue samples will be taken for the duration of that clinical procedure.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prevention of Surgical Site Infections
Keywords
Surgical site infections, Prevention, Prophylaxis, Tumescent, Intravenous, Antibiotic, Absorption, Pharmacokinetics, Bioavailability
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
4 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Tumescent Antibiotic Delivery
Arm Type
Experimental
Arm Description
TAD followed by sequential serum and interstitial tissue fluid sampling for antibiotic concentration of subsequent 24 hours
Arm Title
Intravenous Antibiotic Delivery
Arm Type
Experimental
Arm Description
Intravenous antibiotic delivery of cefazolin with or without metronidazole followed by sequential serum and interstitial tissue fluid sampling for antibiotic concentration of subsequent 24 hours.
Intervention Type
Procedure
Intervention Name(s)
Tumescent Antibiotic Delivery of cefazolin with or without metronidazole
Other Intervention Name(s)
Cefazolin, Metronidazole
Intervention Description
TAD of cefazolin with or without metronidazole followed by sequential serum and interstitial fluid samples over 14 to 24 hours for antibiotic concentrations
Intervention Type
Procedure
Intervention Name(s)
Intravenous Antibiotic Delivery
Intervention Description
Intravenous antibiotic delivery of cefazolin with or without metronidazole followed by sequential serum sampling for antibiotic concentration of subsequent 12 to 24 hours.
Primary Outcome Measure Information:
Title
Area Under the Curve (AUC) of antibiotic concentration as a function of time
Time Frame
24 hours
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Healthy adult
No allergies to cefazolin, metronidazole or lidocaine
Exclusion Criteria:
HIV
Hepatitis C
Diabetes
Facility Information:
Facility Name
Capistrano Surgery Center
City
San Juan Capistrano
State/Province
California
ZIP/Postal Code
92675
Country
United States
12. IPD Sharing Statement
Links:
URL
http://www.tumescent.org
Description
Information about tumescent drug delivery
Learn more about this trial
Tumescent Antibiotic Delivery Pharmacokinetics
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