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D-PLEX 310: Safety and Efficacy of D-PLEX in the Prevention of Post Abdominal Surgery Incisional Infection

Primary Purpose

Abdominal Surgery, Colon Surgery, Post-Op Infection

Status
Completed
Phase
Phase 2
Locations
Israel
Study Type
Interventional
Intervention
D_PLEX
Standard of Care (SoC)
Sponsored by
PolyPid Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Abdominal Surgery focused on measuring Surgical site infection, Abdominal surgery, Colon and small bowl surgery

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Subjects undergoing elective abdominal colon surgery involving resection and anastomosis or a stoma.
  2. Male or non-pregnant female Female of childbearing potential should have a negative serum pregnancy test prior to index procedure and agree to use a highly effective method of contraception consistently and correctly for the duration of the study.
  3. Subjects who sign a written informed consent
  4. Subjects who are willing and able to participate and meet all study requirements.
  5. Survival expectancy of at least 60 days post randomization.

Exclusion Criteria:

  1. Subjects scheduled for abdominal surgery which is classified as emergency.
  2. Subjects with any preoperative active infection that is currently being treated with antibiotics.
  3. Subjects receiving any antibiotic therapy in the past 4 weeks prior to enrolment besides prophylaxis or antibiotic for the treatment of the disease that consists the indication for surgery.
  4. Patients undergoing concomitant additional procedures besides colon resection surgery, e.g. Hyper-thermic Intraperitoneal Chemotherapy, liver resection etc. Female sterilization surgery (i.e. salpingo-oophorectomy, hysterectomy etc.), or involvement of a small bowel procedure or Cholecystectomy may be allowed, pending an advanced consultation and approval from the sponsor.
  5. Subject received chemotherapy within the last 4 weeks of surgery, or radiation for colorectal cancer to the abdomen area, prior to the planned abdominal surgery (neo- adjuvant treatment).
  6. Subjects that received oral or IV doxycycline during the past 4 weeks prior to screening.
  7. Subjects with known sensitivity to doxycycline and/or to the tetracycline family of drugs or to the D-PLEX's excipients.
  8. Subjects with known allergies to more than 3 substances (an allergy questionnaire will be filled in during the screening process).
  9. Subjects with a history of allergic/hypersensitivity reaction to any substance having required hospitalization and/or treatment with intravenous steroids/intramuscular epinephrine or in the opinion of the investigator the patient is at high risk of developing severe allergic/hypersensitivity reactions.
  10. Subjects with uncontrolled Asthma (GINA III-IV).
  11. Subjects with End Stage Renal Disease [Chronic Kidney Disease (CKD) stage 5].
  12. Subjects with chronic urticaria.
  13. Subjects diagnosed with severe neurological/cardiac events within the past 1 year prior to randomization.
  14. Subjects that undergone any abdominal surgery and current planned surgery involves re-opening the scar of prior abdominal surgery.
  15. Any subject with active malignancy or with malignancy that has not been in complete remission for at least 5 years.

    Excluding:

    • subjects with potentially resectable non-metastatic colorectal cancer which consists the indication for surgery. In addition,
    • patients Patients who have had carcinoma in situ of the cervix, squamous cell carcinoma of the skin and basal cell carcinoma of the skin
    • Non-violent cancer that does not require treatment 4 weeks prior to, and throughout the entire study duration will be eligible.
  16. Subjects with other concurrent severe and/or uncontrolled medical condition that could compromise participation in the study (e.g. non-GI active infection, uncontrolled diabetes, uncontrolled hypertension, congestive heart failure, unstable angina, ventricular arrhythmias, active ischemic heart disease, uncompensated cirrhosis, active upper gastrointestinal (GI) tract ulceration).
  17. Psychiatric, addictive, or any other disorder that compromises ability to provide informed consent for participation in this study.
  18. Chronic alcoholic or drug abuse subjects.
  19. Pregnant or breast-feeding women or women of childbearing age who refuse or prohibited of using an effective contraceptive method of birth control (such as double barrier, oral or parenteral hormonal, intrauterine device and spermicide) throughout study participation including safety follow-up period.
  20. Subjects that received any investigational drug within 30 days or 5½ half-lives of enrollment to the study (whichever is longer).
  21. Subjects participating in any other interventional studies.
  22. In the opinion of investigator, subject is not eligible to participate in the study and/or to comply with protocol requirements (e.g. due to a cognitive or medical condition).

Sites / Locations

  • Wolfson MC
  • Meir MC
  • Rabin MC, Campus Beilinson
  • Sheba MC, Tel-Hashomer
  • Kaplan MC
  • Assuta Ramat-HaHayal
  • Tel-Aviv Sourasky MC
  • Assaf-Harofeh MC

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Experimental

Arm Label

Standard of Care (SoC)

D-PLEX + SoC

Arm Description

SOC prophylactic treatment pre-operation will be as per Israeli Ministry of Health and international guidelines: 1st or 2nd generation of Cephalosporine family, plus Metronidazole.

D-PLEX is provided to suitable and willing study subjects as an adjunct to the SoC treatment

Outcomes

Primary Outcome Measures

Infection rate as measured by the proportion of subjects with abdominal incisional infection event
Infection rate as measured by the proportion of subjects with abdominal incisional infection event, as determined by a blinded and independent adjudication committee, within 30 days post abdominal surgery.

Secondary Outcome Measures

Average ASEPSIS assessment score (Additional treatment, Serous discharge, Erythema, Purulent exudate, Separation of deep tissue, Isolation of bacteria, Stay duration as inpatient) during 30 days post-surgery.
ASEPSIS is acronym of wound assessment and treatment parameters (described in the title), 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. Each parameter will be evaluated and numerically scored. Some (Serous discharge & Erythema) will be marked between 0 - 5 and others (Purulent exudate & Separation of deep tissue) are marked between 0 - 10 - based on the proportion of the wound they affect when 0 is none and either 5 or 10 are for over 80% of the wound. Other parameters (Additional antibiotic treatment, a requirement for pus drainage, solation of bacteria & Stay duration as an inpatient) are scored Yes or No. No equals 0. Yes is calculated as either 5 points (for some parameters) or 10 for others. The final score can in the range of 0 - 70. 0 - 10 for wound which heals satisfactorily and over 40 for a severe wound infection.
Incidence of Deep Surgical Site Infection during 30 days post-surgery
Number of deep surgical site infections events during the 30 days post surgery, as confirmed by an independent adjudication committee.
Incidence of Superficial Surgical Site Infection during 30 days post-surgery
Number of superficial surgical site infections events during the 30 days post surgery, as confirmed by an independent adjudication committee.
Mortality rate within 60 days post abdominal surgery
Death from any reason
Susceptibility to Doxycycline
Susceptibility to Doxycycline for any organisms recovered from an abdominal surgery incisional Infection site will be done using a central lab. When an infection is suspected in the incisional wound, a sample will be taken and sent for a bacteriology test in a central lab. Any organism which will grow (if), will be further tested for Doxycycline susceptibility.
Number of overall hospitalization days post surgery
Number of hospitalization days after surgery and until discharge. Will include prolongation of primary hospitalization compared to the average of the rest of the recruited patients and re-admission due to infection
Number of re-admissions due to surgical site infection
Out of the entire hospitalization period, how many days were attributed due to a surgical site infection
Number of antibiotic treatment days post surgery
Number of days antibiotic treatment is administered (any route) to treat an incisional infection.
Time to surgical site infection
Number of days between surgery and a confirmed incisional surgery infection

Full Information

First Posted
June 21, 2018
Last Updated
May 17, 2020
Sponsor
PolyPid Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT03633123
Brief Title
D-PLEX 310: Safety and Efficacy of D-PLEX in the Prevention of Post Abdominal Surgery Incisional Infection
Official Title
Phase II, Multicentre, Randomized, Controlled, Two Arm, Single Blind Study to Assess Safety and Efficacy of D-PLEX Administered Concomitantly With SOC, Compared to SOC, in Prevention of Post Abdominal Surgery Incisional Infection.
Study Type
Interventional

2. Study Status

Record Verification Date
May 2020
Overall Recruitment Status
Completed
Study Start Date
October 4, 2018 (Actual)
Primary Completion Date
September 6, 2019 (Actual)
Study Completion Date
October 6, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
PolyPid Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Subjects who are planned to undergo an abdominal (colon) surgery and who will meet the study entry criteria will be randomly divided into 2 groups: for half D-PLEX will be administered concomitantly with the standard of care (SOC). The other half will receive the Standard of Care treatment. Following the surgery subjects will be followed up for additional 5 visits, at least half are in line with the routine practice of surgery Follow-Ups. Visits will include patient safety and wound assessments.
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. Eligible and willing subjects will be randomly divided, in a single-blinded manor into 2 study arms D-PLEX with SOC or SOC alone. 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, chemistry and PK (for some only) as well as physicians assessment of the incisional wound.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Abdominal Surgery, Colon Surgery, Post-Op Infection
Keywords
Surgical site infection, Abdominal surgery, Colon and small bowl surgery

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
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. Subjects will be randomized to either the investigational arm (SOC + D-PLEX) or to the control arm (SOC only) in a 1:1 ratio. Subjects will be blinded to the study arm.
Masking
Participant
Masking Description
Subject will be blinded to the treatment arm assignment. Physicians which were not part of the team in the surgery room, or from the hospital's infectious diseases dept. will remain blinded to the study arm, and will be those assessing the incisional wound for the study primary endpoint at each follow-up visit post the index surgery. On top, for each suspicion of infection, an external, independent and blinded adjudication committee will be the one making the final decision whether an infection occured or not.
Allocation
Randomized
Enrollment
200 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Standard of Care (SoC)
Arm Type
Other
Arm Description
SOC prophylactic treatment pre-operation will be as per Israeli Ministry of Health and international guidelines: 1st or 2nd generation of Cephalosporine family, plus Metronidazole.
Arm Title
D-PLEX + SoC
Arm Type
Experimental
Arm Description
D-PLEX is provided to suitable and willing study subjects as an adjunct to the SoC treatment
Intervention Type
Drug
Intervention Name(s)
D_PLEX
Intervention Description
D_PLEX is reconstituted into paste and administered in a single application following closure of the fascia, on the fascia suture line, and on the soft tissues of the abdominal wall along the whole length of the surgical wound (including muscle, fat and dermis).
Intervention Type
Other
Intervention Name(s)
Standard of Care (SoC)
Intervention Description
Prophylactic, pre-operation: 1st or 2nd generation of Cephalosporine family, plus Metronidazole. Post-operation: this is each participating center standard practice for this type of procedure
Primary Outcome Measure Information:
Title
Infection rate as measured by the proportion of subjects with abdominal incisional infection event
Description
Infection rate as measured by the proportion of subjects with abdominal incisional infection event, as determined by a blinded and independent adjudication committee, within 30 days post abdominal surgery.
Time Frame
By day 30 post surgery
Secondary Outcome Measure Information:
Title
Average ASEPSIS assessment score (Additional treatment, Serous discharge, Erythema, Purulent exudate, Separation of deep tissue, Isolation of bacteria, Stay duration as inpatient) during 30 days post-surgery.
Description
ASEPSIS is acronym of wound assessment and treatment parameters (described in the title), 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. Each parameter will be evaluated and numerically scored. Some (Serous discharge & Erythema) will be marked between 0 - 5 and others (Purulent exudate & Separation of deep tissue) are marked between 0 - 10 - based on the proportion of the wound they affect when 0 is none and either 5 or 10 are for over 80% of the wound. Other parameters (Additional antibiotic treatment, a requirement for pus drainage, solation of bacteria & Stay duration as an inpatient) are scored Yes or No. No equals 0. Yes is calculated as either 5 points (for some parameters) or 10 for others. The final score can in the range of 0 - 70. 0 - 10 for wound which heals satisfactorily and over 40 for a severe wound infection.
Time Frame
At post surgery study visits : day 1, day 5, day 14 & day 30
Title
Incidence of Deep Surgical Site Infection during 30 days post-surgery
Description
Number of deep surgical site infections events during the 30 days post surgery, as confirmed by an independent adjudication committee.
Time Frame
At study visits: day 1, day 5, day 14 and day 30 post surgery
Title
Incidence of Superficial Surgical Site Infection during 30 days post-surgery
Description
Number of superficial surgical site infections events during the 30 days post surgery, as confirmed by an independent adjudication committee.
Time Frame
At study visits: day 1, day 5, day 14 and day 30 post surgery
Title
Mortality rate within 60 days post abdominal surgery
Description
Death from any reason
Time Frame
During 60 days of study participation
Title
Susceptibility to Doxycycline
Description
Susceptibility to Doxycycline for any organisms recovered from an abdominal surgery incisional Infection site will be done using a central lab. When an infection is suspected in the incisional wound, a sample will be taken and sent for a bacteriology test in a central lab. Any organism which will grow (if), will be further tested for Doxycycline susceptibility.
Time Frame
At study visits: day 1, day 5, day 14 and day 30 post surgery
Title
Number of overall hospitalization days post surgery
Description
Number of hospitalization days after surgery and until discharge. Will include prolongation of primary hospitalization compared to the average of the rest of the recruited patients and re-admission due to infection
Time Frame
During 60 days of study participation
Title
Number of re-admissions due to surgical site infection
Description
Out of the entire hospitalization period, how many days were attributed due to a surgical site infection
Time Frame
During 60 days of study participation
Title
Number of antibiotic treatment days post surgery
Description
Number of days antibiotic treatment is administered (any route) to treat an incisional infection.
Time Frame
During 60 days of study participation
Title
Time to surgical site infection
Description
Number of days between surgery and a confirmed incisional surgery infection
Time Frame
At study visits: day 1, day 5, day 14 and day 30 post surgery

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects undergoing elective abdominal colon surgery involving resection and anastomosis or a stoma. Male or non-pregnant female Female of childbearing potential should have a negative serum pregnancy test prior to index procedure and agree to use a highly effective method of contraception consistently and correctly for the duration of the study. Subjects who sign a written informed consent Subjects who are willing and able to participate and meet all study requirements. Survival expectancy of at least 60 days post randomization. Exclusion Criteria: Subjects scheduled for abdominal surgery which is classified as emergency. Subjects with any preoperative active infection that is currently being treated with antibiotics. Subjects receiving any antibiotic therapy in the past 4 weeks prior to enrolment besides prophylaxis or antibiotic for the treatment of the disease that consists the indication for surgery. Patients undergoing concomitant additional procedures besides colon resection surgery, e.g. Hyper-thermic Intraperitoneal Chemotherapy, liver resection etc. Female sterilization surgery (i.e. salpingo-oophorectomy, hysterectomy etc.), or involvement of a small bowel procedure or Cholecystectomy may be allowed, pending an advanced consultation and approval from the sponsor. Subject received chemotherapy within the last 4 weeks of surgery, or radiation for colorectal cancer to the abdomen area, prior to the planned abdominal surgery (neo- adjuvant treatment). Subjects that received oral or IV doxycycline during the past 4 weeks prior to screening. Subjects with known sensitivity to doxycycline and/or to the tetracycline family of drugs or to the D-PLEX's excipients. Subjects with known allergies to more than 3 substances (an allergy questionnaire will be filled in during the screening process). Subjects with a history of allergic/hypersensitivity reaction to any substance having required hospitalization and/or treatment with intravenous steroids/intramuscular epinephrine or in the opinion of the investigator the patient is at high risk of developing severe allergic/hypersensitivity reactions. Subjects with uncontrolled Asthma (GINA III-IV). Subjects with End Stage Renal Disease [Chronic Kidney Disease (CKD) stage 5]. Subjects with chronic urticaria. Subjects diagnosed with severe neurological/cardiac events within the past 1 year prior to randomization. Subjects that undergone any abdominal surgery and current planned surgery involves re-opening the scar of prior abdominal surgery. Any subject with active malignancy or with malignancy that has not been in complete remission for at least 5 years. Excluding: subjects with potentially resectable non-metastatic colorectal cancer which consists the indication for surgery. In addition, patients Patients who have had carcinoma in situ of the cervix, squamous cell carcinoma of the skin and basal cell carcinoma of the skin Non-violent cancer that does not require treatment 4 weeks prior to, and throughout the entire study duration will be eligible. Subjects with other concurrent severe and/or uncontrolled medical condition that could compromise participation in the study (e.g. non-GI active infection, uncontrolled diabetes, uncontrolled hypertension, congestive heart failure, unstable angina, ventricular arrhythmias, active ischemic heart disease, uncompensated cirrhosis, active upper gastrointestinal (GI) tract ulceration). Psychiatric, addictive, or any other disorder that compromises ability to provide informed consent for participation in this study. Chronic alcoholic or drug abuse subjects. Pregnant or breast-feeding women or women of childbearing age who refuse or prohibited of using an effective contraceptive method of birth control (such as double barrier, oral or parenteral hormonal, intrauterine device and spermicide) throughout study participation including safety follow-up period. Subjects that received any investigational drug within 30 days or 5½ half-lives of enrollment to the study (whichever is longer). Subjects participating in any other interventional studies. In the opinion of investigator, subject is not eligible to participate in the study and/or to comply with protocol requirements (e.g. due to a cognitive or medical condition).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Noam Emanuel, Dr.
Organizational Affiliation
Chief Scientist
Official's Role
Study Director
Facility Information:
Facility Name
Wolfson MC
City
Holon
Country
Israel
Facility Name
Meir MC
City
Kfar Saba
Country
Israel
Facility Name
Rabin MC, Campus Beilinson
City
Petach Tikva
Country
Israel
Facility Name
Sheba MC, Tel-Hashomer
City
Ramat Gan
Country
Israel
Facility Name
Kaplan MC
City
Reẖovot
Country
Israel
Facility Name
Assuta Ramat-HaHayal
City
Tel Aviv
Country
Israel
Facility Name
Tel-Aviv Sourasky MC
City
Tel Aviv
Country
Israel
Facility Name
Assaf-Harofeh MC
City
Zrifin
Country
Israel

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

D-PLEX 310: Safety and Efficacy of D-PLEX in the Prevention of Post Abdominal Surgery Incisional Infection

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