Clinical trial NCT04411199: D-PLEX 312 - Safety and Efficacy of D-PLEX in the Prevention of Post Abdominal Surgery Incisional Infection (SHIELD II)
Official title: D-PLEX 312 - Phase III, Prospective, Multinational, Multicenter, Randomized, Controlled, Two-arm, Double Blind Study to Assess Efficacy and Safety of D-PLEX In Prevention of Post Abdominal Surgery Incisional Infection (SHIELD II)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Surgical Site Infection
Colon Surgery
Abdominal Surgery
Post-Op Infection
Keywords: Surgical site infection
Abdominal surgery
Colon and small bowl surgery
Lead sponsor: PolyPid Ltd.
Sponsor class: INDUSTRY
First posted: 2020-06-02
Enrollment: 800
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: PREVENTION

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.

Eligibility criteria: 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 60 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 6 months prior to randomization.
3. Subjects with any preoperative active infection or who are receiving any antibiotic therapy in the past 1 week prior to randomization, excluding pre-operative prophylaxis.
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 4 weeks of surgery.
6. Subjects who received radiation for colorectal cancer to the abdomen and/or pelvis area, within the last 4 weeks of the planned abdominal surgery.
7. Subjects who received oral or IV Doxycycline or Tetracycline family antibiotics during the past 4 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 3 substances (an allergy questionnaire will be completed during the screening process).
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. Subjects with End Stage Renal Disease (ESRD/ CKD stage 5).
12. Subjects with severe hepatic impairment.
13. Subjects with chronic urticaria.
14. Subjects diagnosed with CVA within the past 6 months prior to randomization.
15. 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 3 years.
16. 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 3 years.

    Excluding: Subjects with potentially resectable non-metastatic colorectal cancer, that is the reason for the index surgery.

    Subjects who have had carcinoma in situ (or other cancer "in situ = Stage 0"), or squamous cell carcinoma of the skin, or basal cell carcinoma of the skin.

    Subjects with any additional non-violent cancer that does not require treatment 4 weeks prior to the surgery, and throughout the entire study duration.
17. Subjects with other concurrent severe and/or uncontrolled medical condition.
18. Psychiatric or any other disorder that compromises ability to provide informed consent for participation in this study.
19. Chronic alcoholic or drug abuse subjects.
20. Pregnant or breast-feeding women or women of child-bearing age who refuse or are prohibited of using an effective contraceptive method of birth control throughout study participation, including the safety follow-up period.
21. Subjects who received any investigational drug within 30 days or 5 half-lives prior to randomization to the study (whichever is longer) and through the study.
22. Subjects participating in any other interventional study.
23. Subjects who in the opinion of Investigator, are not eligible to participate in the study and/or to comply with the protocol requirements (e.g. due to a cognitive or medical condition).

Primary outcomes:
measure: To assess the anti-infective efficacy of D-PLEX over a period of 30 days post operation, by preventing surgical site infection (SSI), defined as superficial and deep infection, in the target incision(s), compared to the SoC treated control.
timeFrame: By day 30 post surgery
measure: Safety of D-PLEX in Prevention of Post Abdominal Surgery
timeFrame: By day 60 post surgery
measure: Safety of D-PLEX in Prevention of Post Abdominal Surgery Incisional
timeFrame: By day 60 post surgery
Secondary outcomes:
measure: Assessment of Infection rate in patient undergoing abdominal colon surgery
timeFrame: At study visits: day 1, day 5, day 14 and day 30 post surgery
Other outcomes:
Locations:
city: Augusta
country: United States
facility: Augusta Univeristy
state: Georgia
city: New Orleans
country: United States
facility: Ochsner Medical Center
state: Louisiana
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Hershey
country: United States
facility: Penn State Health Milton S Hershey Medical Center
state: Pennsylvania
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Banja Luka
country: Bosnia and Herzegovina
facility: University Clinical Centre of the Republic of Srpska
city: Tuzla
country: Bosnia and Herzegovina
facility: University Clinical Center Tuzla
city: Zenica
country: Bosnia and Herzegovina
facility: Cantonal Hospital Zenica
city: Tbilisi
country: Georgia
facility: LLC American Hospital Network
city: Tbilisi
country: Georgia
facility: LTD "Israeli - Georgian Medical Research Clinic Healthycore"
city: Tbilisi
country: Georgia
facility: LTD New Hospitals
city: Tbilisi
country: Georgia
facility: LTD Multiprofile Clinic Consillium Medulla
city: Erlangen
country: Germany
facility: University Hospital Erlangen
city: Muenster
country: Germany
facility: University of Muenster
city: Baja
country: Hungary
facility: Bajai Szent Rokus Korhaz, Sebeszeti Osztaly
city: Budapest
country: Hungary
facility: Uzsoki Utcai Kórház, Sebészeti Osztály
city: Eger
country: Hungary
facility: Heves Varmegyei Markhot Ferenc Oktatokorhaz es Rendelointezet Sebeszeti es Ersebeszeti osztaly
city: Gyöngyös
country: Hungary
facility: Bugát Pál Kórház, Gasztroenterológia - Sebészet
city: Kecskemét
country: Hungary
facility: Bács-Kiskun Megyei Kórház
city: Kistarcsa
country: Hungary
facility: Pest Megyei Flór Ferenc Kórház Sebészeti Osztály
city: Nyíregyháza
country: Hungary
facility: Szabolcs-Szatmar-Bereg Varmegyei Korhazak es Egyetemi Oktatokorhaz, Josa Andras Oktatokorhaz, Sebeszeti Osztaly
city: Szeged
country: Hungary
facility: University of Szeged, Faculty of Medicine, Dep.of Surgery
city: Székesfehérvár
country: Hungary
facility: Fejer-County Saint George University Teaching Hospital, Department of Surgery
city: Drogheda
country: Ireland
facility: Our Lady of Lourdes Hospital
city: Be'er Sheva
country: Israel
facility: Soroka Medical Center
city: Haifa
country: Israel
facility: Bnai Zion Medical Center
city: Haifa
country: Israel
facility: Carmel Medical Center
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: Nahariya
country: Israel
facility: Galilee Medical Center
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
city: Rehovot
country: Israel
facility: Kaplan Medical Center
city: Zerifin
country: Israel
facility: Assaf Harofeh Medical Center
city: Chisinau
country: Moldova, Republic of
facility: IMSP Institutul de Medicina Urgenta
city: Chisinau
country: Moldova, Republic of
facility: IMSP Clinical republican Hospital "Timofei Mosneaga"
city: Chisinau
country: Moldova, Republic of
facility: IMSP Institutul of Oncologic
city: Chisinau
country: Moldova, Republic of
facility: IMSP Spitalul Clinic Republican "Timofei Mosneaga"
city: Chisinau
country: Moldova, Republic of
facility: IMSP Spitalul Clinic Municipal "Gheorghe Paladi"
city: Chisinau
country: Moldova, Republic of
facility: IMSP Spitalul Clinic Municipal "Sfanta Treime"
city: Prilep
country: North Macedonia
facility: PHI General Hospital "Borka Taleski" Prilep
city: Skopje
country: North Macedonia
facility: PHI University Clinic for digestive Surgery
city: Skopje
country: North Macedonia
facility: PHI University Clinic for Surgical Diseases "st.Naum Ohridski - Skopje"
city: Skopje
country: North Macedonia
facility: PHI Clinical Hospital - Shtip
city: Strumica
country: North Macedonia
facility: PHI General Hospital - Strumica
city: Ostrów Mazowiecka
country: Poland
facility: Szpital Powiatowy im. Marii Skłodowskiej - Curie w Ostrowie Mazowieckiej SPZZOZ
city: Łódź
country: Poland
facility: Centrum Medyczne Med-Gastr
city: Aveiro
country: Portugal
facility: Unidade Local de Saúde da Região de Aveiro E. P. E.
city: Braga
country: Portugal
facility: Centro Clinico Academico de Braga Associação - Hospital de Braga
city: Guarda
country: Portugal
facility: Unidade de Saúde Local da Guarda
city: Braşov
country: Romania
facility: Sf. Constantin Hospital
city: Craiova
country: Romania
facility: Spitalul Clinic Judetean de Urgenta Craiova, Sectia Cbirurgie Generala II
city: Craiova
country: Romania
facility: Spitalul Clinic Judetean de Urgenta Craiova, Sectia Chirurgie Generala III
city: Timisoara
country: Romania
facility: Spitalul Clinic JudeIean de Urgenta "Pius Brinzeu", Sectia Chirurgie Generala II
city: Târgu-Mureş
country: Romania
facility: Mures County Clinical Hospital
city: Belgrade
country: Serbia
facility: First Surgical Clinic
city: Nis
country: Serbia
facility: UCC Nis
city: Sremska Kamenica
country: Serbia
facility: Oncology Institute of Vojvodina
city: Sremska Mitrovica
country: Serbia
facility: General Hospital Sremska Mitrovica
city: Valjevo
country: Serbia
facility: Health Center Valjevo
Study officials:
References: