DFA-02 in Patients Undergoing Colorectal Surgery
Primary Purpose
Surgical Site Infection
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
DFA-02
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Surgical Site Infection focused on measuring Surgical site infection, Colorectal surgery
Eligibility Criteria
Inclusion Criteria:
- Males and females 18 years of age or older;
If female, the patient must be:
- postmenopausal (if amenorrheic for < 1 year, postmenopausal status must be confirmed by an elevated follicle stimulating hormone [FSH] level > 30 mIU/mL; if amenorrheic for > 1 year, FSH level not required);
- surgically sterilized (does not have a uterus or has had bilateral tubal ligation); or
- if of child-bearing potential, she must have a negative serum pregnancy test on entry in the study, and agree to use adequate birth control during the study and for 30 days after the administration of study agent. Medically acceptable contraceptives include: (1) surgical sterilization (such as a tubal ligation or hysterectomy), (2) approved hormonal contraceptives (such as birth control pills, patches, implants or injections), (3) barrier methods (such as a condom or diaphragm) used with a spermicide, or (4) an intrauterine device (IUD);
- BMI 25-40, inclusive;
- Scheduled to undergo nonemergent colorectal surgery involving a laparotomy incision of 7 cm or greater (hand-assisted laparoscopic surgery is allowed). List of eligible procedures: left, right or transverse colectomy, segmental/sleeve left colon resection, total abdominal colectomy with ileorectal anastomosis, total abdominal colectomy with ileostomy, total abdominal proctocolectomy, low anterior resection, sigmoid resection, non-emergent Hartmann's procedure, colotomy with polypectomy distal to hepatic flexure, colostomy takedown through laparotomy (not peristomal) incision, ileo-pouch anal anastomosis, abdominal perineal resection of the rectum;
- Willing and able to give informed consent;
- Available for evaluation from baseline until final evaluation at 30 days post surgery.
Exclusion Criteria:
- Known history of hypersensitivity to gentamicin or vancomycin, other aminoglycoside antibiotics or the excipients of the study products (soy bean products or sesame oil);
- Emergency surgery (urgent surgery is allowed if informed consent is obtained and the study procedures can be performed);
- Significant concomitant surgical procedure (Note: concomitant appendectomy, cholecystectomy, oophorectomy, and liver biopsy/wedge resection are allowed);
- Prior laparotomy within the last 60 days of this planned procedure;
- Planned second laparotomy or colorectal surgical procedure (e.g. colostomy or ileostomy takedown) within 30 days of this planned first procedure;
- Expectation that a surgical drain will be placed;
- Preoperative sepsis, severe sepsis, or septic shock;
- Abdominal wall infection/surgical site infection from previous laparotomy/laparoscopy or for any reason;
- Active systemic infection or systemic (oral or intravenous) antibiotic therapy within the 1 week prior to the date of surgery other than specified preoperative antimicrobial prophylaxis (Note: single dose antibiotic therapy for dental or other minor procedures is allowed as is the use of oral non-absorbable antibiotics for preoperative bowel decontamination);
- Requirement for gentamicin or vancomycin preoperative antimicrobial prophylaxis (Note: systemic antibiotic therapy within 72 hours after surgery with gentamicin or vancomycin must be avoided and any systemic antibiotic therapy during that time should be discussed with the Coordinating Center PI or Medical Monitor);
- Requirement for concomitant use or use during the 30 days prior to Day 1 of any prescription or OTC drug that would interfere with the study or place the patient at undue risk. Concurrent systemic or topical use of other potentially neurotoxic, nephrotoxic, and/or ototoxic drugs, such as gentamicin, cisplatin, cephaloridine, kanamycin, amikacin, polymyxin B, colistin, paromomycin, streptomycin, tobramycin, vancomycin, ethacrynic acid, furosemide, and viomycin, should be avoided;
- Preoperative evaluation suggests an intra-abdominal process that might preclude full closure of the skin;
- Ongoing treatment (e.g. chemotherapy, radiation) for non-colorectal cancer;
- History of significant drug or alcohol abuse within the past year;
- Serum Creatinine > 1.3 mg/dL
- Serum Bilirubin > 2.5 times upper limit of normal;
- History of uncontrolled diabetes mellitus (controlled diabetic patients whose hemoglobin A1c is ≤ 9.0% may be included);
- Patients who are immunocompromised including but not limited to systemic corticosteroid use or chemotherapy/radiation during the 30 days prior to surgery, organ transplantation, or HIV infection (Note: inhaled corticosteroids are not exclusionary and single dose use of corticosteroids to prevent PONV is allowed.);
- Any clinically meaningful hearing loss (from Medical History);
- Clinically exclusionary results on clinical laboratory, ECG, or physical examination including but not limited to positive hepatitis B or C or HIV;
- Pregnant or lactating, or if of childbearing potential not practicing a birth control method with a high degree of reliability;
- Refusal to accept medically indicated blood products;
- Participation within 30 days before the start of this study in any experimental drug or device study, or currently participating in a study in which the administration of investigational drug or device within 60 days is anticipated;
- Patients with anterior abdominal wall mesh that is not planned to be completely removed during the planned procedure;
- Unable to participate in the study for any reason in the opinion of the Principal Investigator;
- Postsurgical life expectancy of less than 30 days, in the Investigator's or Sponsor's opinion;
- Expected discharge from the hospital less than 3 days after surgery.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
DFA-02
DFA-02 placebo
Arm Description
Progressive cohorts of 10 subjects (8 active, 2 placebo) receiving 10, 20 , 30 or 40 mL of DFA-02 or matching placebo.
Outcomes
Primary Outcome Measures
Number of Patients With Adverse Events, Laboratory, Physical Examination Changes
Safety and tolerability measured by number of patients with adverse events or changes in laboratory or physical examination findings from baseline (DFA-02 application during surgery on Day 1) to 30 days after surgery.
Area Under Curve (AUC)
Area under the curve (AUC) of plasma gentamicin and vancomycin levels using sparse sampling from baseline (DFA-02 application during surgery on Day 1) to 4 days after surgery
Secondary Outcome Measures
Maximal Plasma Concentration (Cmax)
Maximal plasma concentration (Cmax)of gentamicin and vancomycin using sparse sampling from baseline (DFA-02 application during surgery on Day 1) to 4 days after surgery
Renal Function
Changes in serum creatinine from surgery on Day 1 until 14 days after surgery
Antibiotic Resistance
Methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococcus presence at surgery on Day 1 and 5 days after surgery
Incidence of Surgical Site Infection
The incidence of probable or definite surgical site infection as determined by the Investigator.
Full Information
NCT ID
NCT01496352
First Posted
December 15, 2011
Last Updated
August 15, 2014
Sponsor
Dr. Reddy's Laboratories Limited
Collaborators
Duke Clinical Research Institute
1. Study Identification
Unique Protocol Identification Number
NCT01496352
Brief Title
DFA-02 in Patients Undergoing Colorectal Surgery
Official Title
A Randomized, Double-blind, Placebo Controlled, Safety, Tolerability, and Pharmacokinetic Dose Escalation Study of DFA-02 in Patients Undergoing Colorectal Surgery
Study Type
Interventional
2. Study Status
Record Verification Date
August 2014
Overall Recruitment Status
Completed
Study Start Date
February 2012 (undefined)
Primary Completion Date
April 2013 (Actual)
Study Completion Date
June 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Dr. Reddy's Laboratories Limited
Collaborators
Duke Clinical Research Institute
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a randomized, double-blind, placebo controlled, safety, tolerability, and pharmacokinetic dose escalation Phase II study of DFA-02 in patients undergoing colorectal surgery to evaluate the safety, tolerability and pharmacokinetics of DFA-02.
Detailed Description
Despite antibiotic prophylaxis and improvements in surgical techniques, surgical site infections (SSI) still occur. DFA-02 is a novel bioresorbable modified release gel containing both gentamicin and vancomycin to be applied during surgical incision closure for the prevention of surgical site infections (SSIs) in patients undergoing colorectal surgery.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Surgical Site Infection
Keywords
Surgical site infection, Colorectal surgery
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
DFA-02
Arm Type
Experimental
Arm Description
Progressive cohorts of 10 subjects (8 active, 2 placebo) receiving 10, 20 , 30 or 40 mL of DFA-02 or matching placebo.
Arm Title
DFA-02 placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
DFA-02
Intervention Description
Modified release product containing gentamicin and vancomycin for application at the conclusion of surgery after closure of the fascia and prior to skin closure
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
DFA-02 placebo
Primary Outcome Measure Information:
Title
Number of Patients With Adverse Events, Laboratory, Physical Examination Changes
Description
Safety and tolerability measured by number of patients with adverse events or changes in laboratory or physical examination findings from baseline (DFA-02 application during surgery on Day 1) to 30 days after surgery.
Time Frame
Baseline up to Day 30
Title
Area Under Curve (AUC)
Description
Area under the curve (AUC) of plasma gentamicin and vancomycin levels using sparse sampling from baseline (DFA-02 application during surgery on Day 1) to 4 days after surgery
Time Frame
1, 6, 24, 48 96 hours post-dose
Secondary Outcome Measure Information:
Title
Maximal Plasma Concentration (Cmax)
Description
Maximal plasma concentration (Cmax)of gentamicin and vancomycin using sparse sampling from baseline (DFA-02 application during surgery on Day 1) to 4 days after surgery
Time Frame
1, 6, 24, 48, 96 hours post-dose
Title
Renal Function
Description
Changes in serum creatinine from surgery on Day 1 until 14 days after surgery
Time Frame
Baseline up to Day 14
Title
Antibiotic Resistance
Description
Methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococcus presence at surgery on Day 1 and 5 days after surgery
Time Frame
Baseline up to Day 5
Title
Incidence of Surgical Site Infection
Description
The incidence of probable or definite surgical site infection as determined by the Investigator.
Time Frame
Up to 30 Days After Surgery
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Males and females 18 years of age or older;
If female, the patient must be:
postmenopausal (if amenorrheic for < 1 year, postmenopausal status must be confirmed by an elevated follicle stimulating hormone [FSH] level > 30 mIU/mL; if amenorrheic for > 1 year, FSH level not required);
surgically sterilized (does not have a uterus or has had bilateral tubal ligation); or
if of child-bearing potential, she must have a negative serum pregnancy test on entry in the study, and agree to use adequate birth control during the study and for 30 days after the administration of study agent. Medically acceptable contraceptives include: (1) surgical sterilization (such as a tubal ligation or hysterectomy), (2) approved hormonal contraceptives (such as birth control pills, patches, implants or injections), (3) barrier methods (such as a condom or diaphragm) used with a spermicide, or (4) an intrauterine device (IUD);
BMI 25-40, inclusive;
Scheduled to undergo nonemergent colorectal surgery involving a laparotomy incision of 7 cm or greater (hand-assisted laparoscopic surgery is allowed). List of eligible procedures: left, right or transverse colectomy, segmental/sleeve left colon resection, total abdominal colectomy with ileorectal anastomosis, total abdominal colectomy with ileostomy, total abdominal proctocolectomy, low anterior resection, sigmoid resection, non-emergent Hartmann's procedure, colotomy with polypectomy distal to hepatic flexure, colostomy takedown through laparotomy (not peristomal) incision, ileo-pouch anal anastomosis, abdominal perineal resection of the rectum;
Willing and able to give informed consent;
Available for evaluation from baseline until final evaluation at 30 days post surgery.
Exclusion Criteria:
Known history of hypersensitivity to gentamicin or vancomycin, other aminoglycoside antibiotics or the excipients of the study products (soy bean products or sesame oil);
Emergency surgery (urgent surgery is allowed if informed consent is obtained and the study procedures can be performed);
Significant concomitant surgical procedure (Note: concomitant appendectomy, cholecystectomy, oophorectomy, and liver biopsy/wedge resection are allowed);
Prior laparotomy within the last 60 days of this planned procedure;
Planned second laparotomy or colorectal surgical procedure (e.g. colostomy or ileostomy takedown) within 30 days of this planned first procedure;
Expectation that a surgical drain will be placed;
Preoperative sepsis, severe sepsis, or septic shock;
Abdominal wall infection/surgical site infection from previous laparotomy/laparoscopy or for any reason;
Active systemic infection or systemic (oral or intravenous) antibiotic therapy within the 1 week prior to the date of surgery other than specified preoperative antimicrobial prophylaxis (Note: single dose antibiotic therapy for dental or other minor procedures is allowed as is the use of oral non-absorbable antibiotics for preoperative bowel decontamination);
Requirement for gentamicin or vancomycin preoperative antimicrobial prophylaxis (Note: systemic antibiotic therapy within 72 hours after surgery with gentamicin or vancomycin must be avoided and any systemic antibiotic therapy during that time should be discussed with the Coordinating Center PI or Medical Monitor);
Requirement for concomitant use or use during the 30 days prior to Day 1 of any prescription or OTC drug that would interfere with the study or place the patient at undue risk. Concurrent systemic or topical use of other potentially neurotoxic, nephrotoxic, and/or ototoxic drugs, such as gentamicin, cisplatin, cephaloridine, kanamycin, amikacin, polymyxin B, colistin, paromomycin, streptomycin, tobramycin, vancomycin, ethacrynic acid, furosemide, and viomycin, should be avoided;
Preoperative evaluation suggests an intra-abdominal process that might preclude full closure of the skin;
Ongoing treatment (e.g. chemotherapy, radiation) for non-colorectal cancer;
History of significant drug or alcohol abuse within the past year;
Serum Creatinine > 1.3 mg/dL
Serum Bilirubin > 2.5 times upper limit of normal;
History of uncontrolled diabetes mellitus (controlled diabetic patients whose hemoglobin A1c is ≤ 9.0% may be included);
Patients who are immunocompromised including but not limited to systemic corticosteroid use or chemotherapy/radiation during the 30 days prior to surgery, organ transplantation, or HIV infection (Note: inhaled corticosteroids are not exclusionary and single dose use of corticosteroids to prevent PONV is allowed.);
Any clinically meaningful hearing loss (from Medical History);
Clinically exclusionary results on clinical laboratory, ECG, or physical examination including but not limited to positive hepatitis B or C or HIV;
Pregnant or lactating, or if of childbearing potential not practicing a birth control method with a high degree of reliability;
Refusal to accept medically indicated blood products;
Participation within 30 days before the start of this study in any experimental drug or device study, or currently participating in a study in which the administration of investigational drug or device within 60 days is anticipated;
Patients with anterior abdominal wall mesh that is not planned to be completely removed during the planned procedure;
Unable to participate in the study for any reason in the opinion of the Principal Investigator;
Postsurgical life expectancy of less than 30 days, in the Investigator's or Sponsor's opinion;
Expected discharge from the hospital less than 3 days after surgery.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kent Allenby, MD
Organizational Affiliation
Dr. Reddy's Laboratories
Official's Role
Study Director
Facility Information:
City
Florence
State/Province
Alabama
Country
United States
City
Tampa
State/Province
Florida
Country
United States
City
Columbus
State/Province
Ohio
Country
United States
City
Bellaire
State/Province
Texas
Country
United States
City
Temple
State/Province
Texas
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
27313846
Citation
Bennett-Guerrero E, Minkowitz HS, Segura-Vasi AM, Marcet JE, White JA, Corey GR, Allenby KS. A randomized, double-blind, placebo controlled safety, tolerability, and pharmacokinetic dose escalation study of a gentamicin vancomycin gel in patients undergoing colorectal surgery. Perioper Med (Lond). 2016 Jun 16;5:17. doi: 10.1186/s13741-016-0043-2. eCollection 2016.
Results Reference
derived
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DFA-02 in Patients Undergoing Colorectal Surgery
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