Surgical Site Infections
Conditions
Brief summary
This is a randomized, blinded, placebo and standard of care controlled study of the efficacy of a novel antibiotic containing gel compared to placebo gel in preventing surgical site infection after abdominal surgery. patients will be randomized to active or placebo gel in a double-blind manner. The gel will be applied a single time in the incision during closure at the end of surgery. A cohort of patients will also be randomized to standard of care, saline irrigation at prior to skin closure, in an open manner. The efficacy, safety and tolerability of the active gel will be assessed compared to the control group (combined placebo gel and standard of care groups). Patients will be randomized to DFA-02 active gel: placebo gel: standard of care in a 4:1:1 ratio.
Interventions
DRUGDFA-02 Antibiotic Gel
DRUGDFA-02 Placebo Gel
Sponsors
Duke Clinical Research Institute
Dr. Reddy's Laboratories Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Males and females 18 years of age or older; 2. If female, the subject must be postmenopausal, surgically sterilized or, if of child-bearing potential, she must have a negative serum or urine pregnancy test within 48 hours of surgery and agree to use adequate birth control during the study and for 30 days after the administration of study agent; 3. Body mass index (BMI) ≥ 20; 4. Scheduled to undergo non-emergent abdominal surgery involving a planned incision of 7 cm or greater; 5. Willing and able to give informed consent; 6. Available for evaluation from Baseline until final evaluation at 30 days post-surgery.
Exclusion criteria
1. Known hypersensitivity to gentamicin, vancomycin, other aminoglycoside antibiotics or the excipients of the study products; 2. Emergency surgery; 3. Significant concomitant surgical procedure; 4. Prior laparotomy within the last 60 days of the planned procedure; 5. Planned second laparotomy or abdominal surgical procedure within 30 days of the planned first procedure; 6. Expectation that a surgical drain will be placed in the incision; 7. Preoperative sepsis, severe sepsis, or septic shock; 8. Abdominal wall infection/surgical site infection from previous laparotomy/laparoscopy or for any reason; 9. 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; 10. Requirement for gentamicin or vancomycin preoperative antimicrobial prophylaxis; 11. Concurrent systemic use of other potentially neurotoxic, nephrotoxic, and/or ototoxic drugs; 12. Preoperative evaluation suggesting an intra-abdominal process that might preclude full closure of the skin; 13. Ongoing treatment (e.g. chemotherapy, radiation) for non-colorectal cancer; 14. History of significant drug or alcohol abuse; 15. Serum Creatinine \> 1.8 mg/dL; 16. Serum Bilirubin \> 2.5 times upper limit of normal; 17. Subjects 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; 18. Known history of HIV; 19. Pregnant or lactating, or if of childbearing potential not practicing a birth control method with a high degree of reliability; 20. Refusal to accept medically indicated blood products; 21. 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; 22. Unable to participate in the study for any reason in the opinion of the Principal Investigator; 23. Postsurgical life expectancy of less than 30 days; 24. Expected discharge from the hospital less than 3 days after surgery.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Patients With Surgical Site Infections | Within 30 days of surgery |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Adverse Events | Within 30 days of surgery | — |
| Change in Serum Creatinine Measurements From Baseline | Within 4 days of surgery | Change from baseline in micromoles/liter |
| Cumulative ASEPSIS Score for Each Patient | Through post-operative Day 4 | Total ASEPSIS score with a range of 0-65 points with lower scores being better. The score is the sum of: Antibiotic Use (10 points), Drainage of Pus Under Local Anesthesia (5 points), Debridement Under General Anesthesia (10 points), Serous Discharge (5 points), Erythema (5 points), Purulent Exudate (5 points), Separation of Deep Tissues (10 points) and Isolation of Bacteria from Discharge (10 points). Source: Wilson AP, Treasure T, Sturridge MF, Gruneberg RN. Lancet. 1986:1(8476):311-3. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| DFA-02 Antibiotic Gel Up to 20 mL of DFA-02 antibiotic gel will be placed in the surgical incision after closure of the fascia and before skin closure.
DFA-02 Antibiotic Gel | 296 |
| DFA-02 Placebo Gel Up to 20 mL of DFA-02 placebo gel will be placed in the surgical incision after closure of the fascia and before skin closure.
DFA-02 Placebo Gel | 71 |
| Standard of Care Prior to final closure of the surgical incision, the incision will be irrigated with normal saline and no gel will be applied. | 78 |
| Total | 445 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | 30-Day Visit Too Early (< 28 Days) | 1 | 0 | 0 |
| Overall Study | Death | 2 | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 1 | 0 |
| Overall Study | Physician Decision | 3 | 4 | 2 |
| Overall Study | Protocol Violation | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | DFA-02 Antibiotic Gel | Total | Standard of Care | DFA-02 Placebo Gel |
|---|---|---|---|---|
| Age, Continuous | 60.1 years STANDARD_DEVIATION 14.6 | 59.8 years STANDARD_DEVIATION 14.8 | 59.6 years STANDARD_DEVIATION 14.7 | 58.8 years STANDARD_DEVIATION 15.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 8 Participants | 9 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 31 Participants | 45 Participants | 4 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 255 Participants | 389 Participants | 74 Participants | 60 Participants |
| Region of Enrollment United States | 296 participants | 445 participants | 78 participants | 71 participants |
| Sex: Female, Male Female | 142 Participants | 220 Participants | 45 Participants | 33 Participants |
| Sex: Female, Male Male | 154 Participants | 225 Participants | 33 Participants | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 267 / 284 | 61 / 64 | 86 / 93 |
| serious Total, serious adverse events | 59 / 284 | 14 / 64 | 21 / 93 |
Outcome results
Primary
Number of Patients With Surgical Site Infections
Time frame: Within 30 days of surgery
Population: The number of SSIs from the day of surgery to 30 days post-op could only be assessed in the 427 completed patients. Central adjudication by the Clinical Events Committee was not able to assess the presence or absence of SSI for two patients, one in the DFA-02 group and one in the SOC group so the total analyzed is only 425.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DFA-02 Antibiotic Gel | Number of Patients With Surgical Site Infections | 42 participants |
| DFA-02 Placebo Gel | Number of Patients With Surgical Site Infections | 14 participants |
| Standard of Care | Number of Patients With Surgical Site Infections | 25 participants |
Secondary
Change in Serum Creatinine Measurements From Baseline
Change from baseline in micromoles/liter
Time frame: Within 4 days of surgery
Population: 402 of the 445 patients had both baseline and post-operative creatinine measurements. Safety analyses were as treated so patients randomized to gel but did not receive it in surgery were counted in the SOC group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DFA-02 Antibiotic Gel | Change in Serum Creatinine Measurements From Baseline | -10.2 micromoles/liter | Standard Deviation 18.2 |
| DFA-02 Placebo Gel | Change in Serum Creatinine Measurements From Baseline | -9.9 micromoles/liter | Standard Deviation 12.8 |
| Standard of Care | Change in Serum Creatinine Measurements From Baseline | -10.2 micromoles/liter | Standard Deviation 27 |
Secondary
Cumulative ASEPSIS Score for Each Patient
Total ASEPSIS score with a range of 0-65 points with lower scores being better. The score is the sum of: Antibiotic Use (10 points), Drainage of Pus Under Local Anesthesia (5 points), Debridement Under General Anesthesia (10 points), Serous Discharge (5 points), Erythema (5 points), Purulent Exudate (5 points), Separation of Deep Tissues (10 points) and Isolation of Bacteria from Discharge (10 points). Source: Wilson AP, Treasure T, Sturridge MF, Gruneberg RN. Lancet. 1986:1(8476):311-3.
Time frame: Through post-operative Day 4
Population: Safety analyses were as treated so patients who were randomized to gel but did not receive it are counted as SOC. For 4 patients, the actual treatment given could not be assigned due to conflicting data excluding them from the analysis leaving 441 subjects out of the 445 randomized.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DFA-02 Antibiotic Gel | Cumulative ASEPSIS Score for Each Patient | 17.5 units on a scale | Standard Deviation 8.1 |
| DFA-02 Placebo Gel | Cumulative ASEPSIS Score for Each Patient | 18.5 units on a scale | Standard Deviation 3.5 |
| Standard of Care | Cumulative ASEPSIS Score for Each Patient | 23.0 units on a scale | Standard Deviation 3.5 |
Secondary
Number of Patients With Adverse Events
Time frame: Within 30 days of surgery
Population: The safety analysis was as treated. For 4 patients the actual treatment given could not be assigned due to conflicting data excluding them from the analysis leaving 441 subjects out of the 445 randomized. The DFA-02 Gel and Placebo Gel groups were decreased as the patients who did not receive gel were counted in the SOC group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DFA-02 Antibiotic Gel | Number of Patients With Adverse Events | 267 participants |
| DFA-02 Placebo Gel | Number of Patients With Adverse Events | 61 participants |
| Standard of Care | Number of Patients With Adverse Events | 86 participants |