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Direct Antibiotic Delivery of Cefazolin Into Soft Tissue Infections Using Subcutaneous Injection and Ultrasonic Dispersion (DAD)

Expanded access is currently available for this treatment.
Verified November 2014 by Silberg, Barry N., M.D.
Sponsor:
Information provided by (Responsible Party):
Barry N. Silberg, M.D., F.A.C.S., Silberg, Barry N., M.D.
ClinicalTrials.gov Identifier:
NCT01238276
First received: November 8, 2010
Last updated: November 19, 2014
Last verified: November 2014
  Purpose

This study focuses on a new drug delivery system (Direct Antibiotic Delivery) to treat soft tissue infections. In this study, cefazolin is delivered directly to the target tissues using subcutaneous injection of antibiotic solution and then dispersed using high-frequency external ultrasound. Using this system, a much higher concentration of antibiotic can be achieved than through traditional treatment methods.

Unlike traditional delivery methods, Direct Antibiotic Delivery does not rely on blood supply and is beneficial for subjects with Diabetes or subjects who have received radiation therapy and blood supply is limited.


Condition Intervention Phase
Infection, Soft Tissue
Infection, Wound
Cellulitis
Foot Ulcer, Diabetes
Drug: Cefazolin
Device: Silberg Tissue Preparation System
Phase 1

Study Type: Expanded Access     What is Expanded Access?
Official Title: Direct Antibiotic Delivery of Cefazolin Into Soft Tissue Infections Using Subcutaneous Injection and Ultrasonic Dispersion

Resource links provided by NLM:


Further study details as provided by Silberg, Barry N., M.D.:

Study Start Date: January 2014
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Cefazolin
    Cefazolin is approved for clinical use for some bacterial infections. The standard routes of administration are Intramuscular (IM) and intravenous (IV). For this study, the route of administration will be delivered using the Silberg TPS, which delivers the cefazolin by subcutaneous injection followed by external ultrasonic dispersion. The concentration delivered is one gram/100 ml saline. Cefazolin can safely be given IM at the much higher concentration of one gram/2.5 ml of saline. The maximum dose that may be administered is three gram in 300 ml, which is within the approved guidelines of a daily dose. The concentration of antibiotic will be the same; only the dose may vary depending on the size of the wound or area of induration. Each subject will receive only one treatment in this study.
    Other Names:
    • Ancef
    • Kefzol
    Device: Silberg Tissue Preparation System

    The TPS is FDA approved for the subcutaneous infusion and ultrasonic dispersion of tumescent fluid excluding the parenteral delivery of drugs. Under this study, the TPS is a device to deliver cefazolin by subcutaneous injection followed by external ultrasonic dispersion. The TPS consists of a medical grade peristaltic pump that is used to infuse antibiotic solution using a sterile blunt-tipped infusion cannula into a superficial subcutaneous plane. After the cannula has been removed, high frequency external ultrasound is delivered transcutaneously over the area of infusion in order to disperse the antibiotic solution. The power density is within the range allowed for physical therapy.

    Delivering a higher concentration of antibiotic directly into the infected soft tissues independent of blood supply allows a significantly greater concentration of antibiotic to be delivered to the target tissues than can be achieved by any other method.

    Other Names:
    • Silberg TPS (K023083)
    • Tissue Preparation System
    • TPS
    • Mettler ME800
Detailed Description:

In this study, the DOSAGE of cefazolin that is delivered is a fraction of that which is already FDA approved for intramuscular (IM) administration. However, the CONCENTRATION in the target area is much higher than what can be achieved through intravenous (IV) administration, while still being far less than what is approved for IM administration.

Previous to this study, cefazolin was considered to be ineffective in treating Methicillin-resistant Staphylococcus aureus (MRSA) as it had only been tested at the concentrations that were attainable by traditional methods. Through our study and laboratory tests conducted at the Harford Hospital, Connecticut, we have confirmed that cefazolin can be effective against even the most resistant strains of MRSA if a high enough concentration is obtained.

Under this study, treatment is only available to subjects that have already undergone standard therapy, but were not able to resolve the infection.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Subjects with pathologically confirmed presence of serious or immediately life-threatening soft tissue infection, cellulitis or open wound caused by bacteria for which cefazolin at this concentration is likely to have activity to inhibit the bacteria, for example, Staphylococcus species or Streptococcus species, Escherichia coli, Proteus mirabilis.
  • Wounds must demonstrate the presence of skin and skin structure infection, which may be demonstrated by one or more of the following: Culture results as aforementioned, swelling of the tissues, discoloration, open wounds, and/or drainage, which may or may not be associated with pain and/or tenderness.
  • Confirmed presence of soft tissue cellulitis caused by bacteria for which cefazolin is likely to have activity to inhibit the bacteria will be evidenced by microbiologic cultures taken no greater than ten (10) days prior to treatment.
  • Subject must have previously been treated by a qualified licensed physician using traditional surgical and/or medical treatments, which may include courses of IV antibiotics, but where Subject was unable to resolve their infection through traditional surgical and/or medical treatments for soft tissue cellulitis caused by bacteria for which cefazolin is likely to have activity to inhibit the bacteria at a maximum concentration of 1 gram per 100 ml saline, as demonstrated by the presence of induration, redness, open wounds, and/or soft tissue swelling.
  • Subject must be referred by his or her treating physician to the Wound Care Center of the investigational hospital.
  • The Wound Care Center of the investigational hospital has confirmed that standard therapies have failed to cure the subject's infection and the infection is still present.
  • Subjects are not on concomitant antibacterial drugs since these drugs have failed to treat the subject's infection.
  • Subject may be male or female and must be at least 18 years of age.
  • Subject must sign informed consent as approved by the Institutional Review Board (IRB).

Exclusion Criteria:

  • Subjects who have not received treatment by traditional surgical and/or medical therapies.
  • Subjects who are allergic to cefazolin.
  • Subjects who have a serious allergy to penicillin.
  • Subjects with infections that involve body cavities.
  • Subjects designated to be vulnerable, i.e., pregnant women, subjects under the age of 18, and subjects who need to have consent provided by a Legally Authorized Representative (LAR).
  • Subjects who are unable or unwilling to comply with the protocol.
  • Subjects who have a history of clinically significant or uncontrolled cardiac disease, including congestive heart failure, angina, myocardial infarction, arrhythmia, including New York Heart Association (NYHA) functional classification of 3.
  • Subjects who have any other life-threatening illness or organ system dysfunction, which, in the opinion of the investigator, would either compromise subject safety or interfere with the evaluation of the safety of the test drug.
  • Subjects who cannot understand English.
  • Subjects who have received a treatment under this study are not eligible for re-admittance for thirty (30) days from the date of their last treatment.
  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: NCT01238276

Contacts
Contact: Barry N Silberg, M.D. 707-528-0911 drsilberg@silberg.com
Contact: Michele Brule, MBA 707-479-5928 mbrule@sonic.net

Locations
United States, California
TBD
Santa Rosa, California, United States, 95403
Contact: TBD , M.D.         
Principal Investigator: Barry N Silberg, MD, FACS         
Sponsors and Collaborators
Silberg, Barry N., M.D.
Investigators
Principal Investigator: Barry N Silberg, MD Palm Drive Hospital, Santa Rosa Memorial Hospital, Sutter Health
Study Director: Roger A Klein, MD TBD
  More Information

Additional Information:
Publications:
Responsible Party: Barry N. Silberg, M.D., F.A.C.S., Sponsor/Investigator, Silberg, Barry N., M.D.
ClinicalTrials.gov Identifier: NCT01238276     History of Changes
Other Study ID Numbers: IND 75,736
Study First Received: November 8, 2010
Last Updated: November 19, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Silberg, Barry N., M.D.:
soft tissue infection
wound infection
cellulitis
foot ulcer
Diabetes
antibiotics
cefazolin
cephazolin
Ancef
Kefzol
subcutaneous fluid administration
ultrasound
MRSA
Methicillin-resistant Staphylococcus aureus

Additional relevant MeSH terms:
Cellulitis
Communicable Diseases
Foot Ulcer
Infection
Soft Tissue Infections
Wound Infection
Connective Tissue Diseases
Foot Diseases
Inflammation
Leg Ulcer
Pathologic Processes
Skin Diseases
Skin Diseases, Infectious
Skin Ulcer
Suppuration
Wounds and Injuries
Anti-Bacterial Agents
Antibiotics, Antitubercular
Cefazolin
Anti-Infective Agents
Antitubercular Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014