Abdominal Surgery, Colon Surgery, Post-Op Infection, Surgical Site Infection
Conditions
Keywords
Surgical site infection, Abdominal surgery, Colon and small bowl surgery
Brief summary
Phase III, Prospective, Multinational, Multicenter, Randomized, Controlled, Two-arm, Double Blind Study to Assess Efficacy and Safety of D-PLEX Administered Concomitantly with the Standard of Care (SoC), Compared to a SoC Treated Control Arm, in Prevention of Post Abdominal Surgery Incisional Infection.
Detailed description
D-PLEX is a new formulation of extended controlled release of Doxycycline in the applied area for about 30 days. This study is aimed to assess the safety and efficacy of D-PLEX in prevention of post abdominal surgery incisional infection. The study population includes male and female, 18 years old and above at screening, undergoing an elective colorectal surgery involving colon or rectal resection, with or without a stoma formation, that includes at least 1 incision that is \> 20cm (target incision). Eligible and willing subjects will be randomly allocated into 2 blinded study arms, either to the investigational arm (D-PLEX + SoC) or to the control arm (SoC only) in a 1:1 ratio. Subjects will be stratified by type of prophylactic SoC (IV antibiotic only, IV antibiotic with mechanical bowel preparation or IV antibiotic with oral antibiotics combined with mechanical bowel preparation) and by region (US versus Europe + Israel). D-PLEX will be applied during the surgery at the final stage of incision closure. All patients will be followed up for additional 5 visits over 2 months, for safety and incisional wound assessment. This will include blood tests for hematology and chemistry as well as physician's assessment of the incisional wound.
Interventions
DRUGD-PLEX
D-PLEX is a new formulation of extended release of Doxycycline.
OTHERStandard of Care (SoC)
prophylactic, pre-operation per institution guidelines
Sponsors
PolyPid Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
This is a double-blind clinical trial. The sponsor, the subjects, outcomes assessor and all staff involved in the collection and recording of the clinical and laboratory data, based on which the independent adjudication committee will perform their assessment, will be blind to treatment assignment. In addition, all aspects of data management and clean-up will be done in blinded datasets. The study site personnel, who perform the index surgery (Operation room staff), will be trained not to disclose the treatment arm to the blinded Investigator, to the subject, his/her family, to other health care providers not present during the surgery or to the study Sponsor representatives. Wound assessment throughout the study follow-up visits will be done by a blinded Investigator, that will not be involved in the surgery. An emergency card containing the Study Name, NIH number, Center Name/number, PI's name and contact details will be provided to the subjects.
Intervention model description
Males and females, \>18 years old, undergoing scheduled abdominal colon surgery involving resection and anastomosis or a stoma, who meet the inclusion criteria and none of the exclusion criteria and provide signed informed consent will be enrolled in the study.
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
1. Subjects undergoing an elective colorectal surgery involving resection, with or without a stoma formation, that includes at least 1 abdominal incision that is \>20cm (target incision). 2. Subjects are preoperative hemodynamically stable. (BP≤180/110 and \>90/60 mmHg, and HR≤120 and \>60 bpm, and temperature ≤37.50C and \>35.50C). 3. Male or non-pregnant female. 4. Female of child-bearing potential should have a negative pregnancy test (serum or urine dipstick) prior to index procedure. 5. Subjects' age 18 years old and above at screening. 6. Subjects who sign the written Informed Consent Form. 7. Subjects who are willing and able to participate and meet all study requirements. 8. Survival expectancy of at least sixty days post randomization.
Exclusion criteria
1. Subjects with suspected/diagnosed intestinal perforation, intra-abdominal abscess, or any emergency/urgent colorectal surgery with acute intestinal obstruction (ex. toxic colitis, ileus/sub-ileus, megacolon, diverticulitis, volvulus, etc.) 2. Subjects who underwent an intra-abdominal surgery within the last six months prior to randomization. 3. Subjects with any preoperative active infection or who are receiving any antibiotic therapy in the past one week prior to randomization, excluding pre-operative prophylaxis or antibiotics for the treatment of the disease that is the indication for surgery. 4. Subjects undergoing concomitant major procedures in addition to the colorectal resection. Female sterilization surgeries (i.e. salpingo-oophorectomy etc.), involvement of a small bowel procedure or cholecystectomy may be allowed, pending an advanced consultation and approval from the Sponsor. 5. Subjects who received any anti-cancer treatment within the last four weeks of surgery. 6. Subjects who received radiation for colorectal cancer to the abdomen and/or pelvis area, within the last four weeks of the planned abdominal surgery. 7. Subjects who received oral or IV Doxycycline or Tetracycline family antibiotics during the past four weeks prior to randomization. 8. Subjects with known allergy to Doxycycline and/or to the tetracycline family of drugs or to the D-PLEX's excipients. 9. Subjects with known allergies to more than three substances. 10. Subjects with history of severe allergic reaction to any substance, having required treatment with intravenous steroids/intramuscular epinephrine, or who in the opinion of the PI is at high risk of developing severe allergic reactions. 11. Uncontrolled medical condition. 12. Subjects who underwent any abdominal surgery and current planned index surgery involves re-opening the scar of a prior abdominal surgery performed within the last three years. 13. Any subject with an active malignancy or with malignancy that has not been in complete clinical remission and without maintenance chemo or immunotherapy for at least three years.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Infection Rate as Measured by the Percentage of Subjects With SSI Event in the Target Incision Within 30 Days Post Index Surgery or Re-interventions or Death [for Any Reason] in the Population of Subjects With Target Incision Length >20 cm | By day 30 post surgery | The primary analysis is based on a composite treatment-failure (Yes/No) variable, indicating if a subject had at least one treatment-failure event, defined as follows: SSI, occurring within 30 days post abdominal surgery and determined by a blinded and independent adjudication committee, death (from any reason) or re-intervention at the target incision site within 30 days post surgery will be considered a treatment failure for the primary ITT analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Subjects With at Least One SSI Event in the Target Incision | By day 30 post surgery | Infection rate as measured by the proportion of subjects with at least one abdominal incisional infection event, occurring within 30 days post abdominal (index) surgery and determined by a blinded and independent adjudication committee. \[abdominal incisional infection is defined as Deep Incisional Surgical Site Infection (DSSI) and/or Superficial Incisional Surgical Site Infection (SSSI)\]. |
| Infection Rate as Measured by the Percentage of Subjects With SSI Event in the Target Incision Within 30 Days Post Index Surgery or Re-interventions or Death [for Any Reason] in the Population of Subjects With Target Incision Length >7 cm | 30 days post surgery | The primary analysis is based on a composite treatment-failure (Yes/No) variable, indicating if a subject had at least one treatment-failure event, defined as follows: SSI, occurring within 30 days post abdominal surgery and determined by a blinded and independent adjudication committee, and target incision length \> 7 cm, death (from any reason) or re-intervention at the target incision site within 30 days post surgery will be considered a treatment failure. |
| Percentage of Subjects With at Least 1 Score of ASEPSIS> 20, Within 30 Days Post Abdominal (Index) Surgery | 30 days post surgery | ASEPSIS (Additional Treatment, Serous Discharge, Erythema, Purulent Exudates, Separation of Deep Tissue, Isolation of Bacteria, Stay as In Patient) is an acronym of wound assessment and treatment parameters, which provides numerically score during an inspection of the surgical site. The final score is being interpreted to severity of wound appearance and the clinical consequences of the infection. |
Countries
Bosnia and Herzegovina, Georgia, Germany, Hungary, Ireland, Israel, Moldova, North Macedonia, Poland, Portugal, Romania, Serbia, United States
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 65.6 years STANDARD_DEVIATION 11.9 |
| BMI | 26.81 kg/m^2 STANDARD_DEVIATION 4.77 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 973 Participants |
| Region of Enrollment Bosnia and Herzegovina | 34 participants |
| Region of Enrollment Georgia | 14 participants |
| Region of Enrollment Germany | 1 participants |
| Region of Enrollment Hungary | 95 participants |
| Region of Enrollment Ireland | 5 participants |
| Region of Enrollment Israel | 34 participants |
| Region of Enrollment Moldova | 117 participants |
| Region of Enrollment North Macedonia | 113 participants |
| Region of Enrollment Poland | 23 participants |
| Region of Enrollment Portugal | 24 participants |
| Region of Enrollment Romania | 50 participants |
| Region of Enrollment Serbia | 135 participants |
| Region of Enrollment United States | 3 participants |
| Sex: Female, Male Female | 219 Participants |
| Sex: Female, Male Male | 268 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 10 / 481 | 19 / 493 |
| other Total, other adverse events | 399 / 481 | 401 / 493 |
| serious Total, serious adverse events | 75 / 481 | 85 / 493 |
Outcome results
None listed