D-PLEX 312 - Safety and Efficacy of D-PLEX in the Prevention of Post Abdominal Surgery Incisional Infection (SHIELD II)
- Conditions
- Surgical Site InfectionColon SurgeryAbdominal SurgeryPost-Op Infection
- Interventions
- Other: Standard of Care (SoC)
- Registration Number
- NCT04411199
- Lead Sponsor
- PolyPid Ltd.
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 624
- 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).
- 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).
- Male or non-pregnant female.
- Female of child-bearing potential should have a negative pregnancy test (serum or urine dipstick) prior to index procedure.
- Subjects' age 18 years old and above at screening.
- Subjects who sign the written Informed Consent Form.
- Subjects who are willing and able to participate and meet all study requirements.
- Survival expectancy of at least 60 days post randomization.
Exclusion criteria:
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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.)
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Subjects who underwent an intra-abdominal surgery within the last 6 months prior to randomization.
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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.
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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 .
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Subjects who received any anti-cancer treatment within the last 4 weeks of surgery.
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Subjects who received radiation for colorectal cancer to the abdomen and/or pelvis area, prior to the planned abdominal surgery.
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Subjects who received oral or IV Doxycycline or Tetracycline family antibiotics during the past 4 weeks prior to randomization.
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Subjects with known allergy to Doxycycline and/or to the tetracycline family of drugs or to the D-PLEX's excipients.
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Subjects with known allergies to more than 3 substances (an allergy questionnaire will be completed during the screening process).
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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.
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Subjects with End Stage Renal Disease (ESRD/ CKD stage 5).
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Subjects with severe hepatic impairment.
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Subjects with chronic urticaria.
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Subjects diagnosed with CVA within the past 6 months prior to randomization.
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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.
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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.
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Subjects with other concurrent severe and/or uncontrolled medical condition.
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Psychiatric or any other disorder that compromises ability to provide informed consent for participation in this study.
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Chronic alcoholic or drug abuse subjects.
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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.
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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.
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Subjects participating in any other interventional study.
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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).
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description D-PLEX+SoC Standard of Care (SoC) D-PLEX is provided to suitable and willing study subjects as an adjunct to the SoC treatment Standard of Care Standard of Care (SoC) The SoC for prophylactic antibiotic treatment is based on international guidelines D-PLEX+SoC D-PLEX D-PLEX is provided to suitable and willing study subjects as an adjunct to the SoC treatment
- Primary Outcome Measures
Name Time Method 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. By day 30 post surgery Infection rate as measured by the proportion of subjects with at least one abdominal incisional infection event, as determined by a blinded and independent adjudication committee, within 30 days post abdominal surgery. \[abdominal incisional infection is composed of Deep Incisional Surgical Site Infection (DSSI) and Superficial Incisional Surgical Site Infection (SSSI)\].within 30 days post abdominal surgery and determined by a blinded and independent adjudication committee.
All-cause mortality and re-interventions in the target incision within 30 days post index surgery will be analysed as treatment failure.
Incisional infection event only, occurred within 30 days post abdominal surgery and determined by a blinded and independent adjudication committee.
\[abdominal incisional infection is defined as Deep Incisional Surgical Site Infection (DSSI) and/or Superficial Incisional Surgical Site Infection (SSSI)\].Safety of D-PLEX in Prevention of Post Abdominal Surgery By day 60 post surgery Safety parameters will be evaluated by adverse events
Safety of D-PLEX in Prevention of Post Abdominal Surgery Incisional By day 60 post surgery Incisional wound healing will be assessed by a blinded Investigator, using a visual examination as well as Modified Vancouver Scar Scale wound assessment questionnaires. The questionnaire has a numeric scale from 0-4 in Vascularity, Pigmentation, Pliability and height
- Secondary Outcome Measures
Name Time Method Assessment of Infection rate in patient undergoing abdominal colon surgery At study visits: day 1, day 5, day 14 and day 30 post surgery Infection rate as measured by the proportion of subjects with at least one abdominal incisional infection event only, occurred within 30 days post abdominal surgery and determined by a blinded and independent adjudication committee.
\[abdominal incisional infection is defined as Deep Incisional Surgical Site Infection (DSSI) and/or Superficial Incisional Surgical Site Infection (SSSI)\].
Trial Locations
- Locations (68)
Pest Megyei Flór Ferenc Kórház Sebészeti Osztály
🇭🇺Kistarcsa, Hungary
Augusta Univeristy
🇺🇸Augusta, Georgia, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Ochsner Medical Center
🇺🇸New Orleans, Louisiana, United States
Penn State Health Milton S Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Baptist Medical Group Oncology Surgical Associates
🇺🇸Memphis, Tennessee, United States
University Clinical Centre of the Republic of Srpska
🇧🇦Banja Luka, Bosnia and Herzegovina
General Hospital "Prim. dr. Abdulah Nakas"
🇧🇦Sarajevo, Bosnia and Herzegovina
University Clinical Center Tuzla
🇧🇦Tuzla, Bosnia and Herzegovina
Cantonal Hospital Zenica
🇧🇦Zenica, Bosnia and Herzegovina
LLC American Hospital Network
🇬🇪Tbilisi, Georgia
LTD "Israeli - Georgian Medical Research Clinic Healthycore"
🇬🇪Tbilisi, Georgia
LTD New Hospitals
🇬🇪Tbilisi, Georgia
LTD Multiprofile Clinic Consillium Medulla
🇬🇪Tbilisi, Georgia
University Hospital Erlangen
🇩🇪Erlangen, Germany
Saarland University Hospital
🇩🇪Homburg/Saar, Germany
University of Muenster
🇩🇪Muenster, Germany
Bajai Szent Rokus Korhaz, Sebeszeti Osztaly
🇭🇺Baja, Hungary
Uzsoki Utcai Kórház, Sebészeti Osztály
🇭🇺Budapest, Hungary
Heves Varmegyei Markhot Ferenc Oktatokorhaz es Rendelointezet Sebeszeti es Ersebeszeti osztaly
🇭🇺Eger, Hungary
Szabolcs-Szatmar-Bereg Varmegyei Korhazak es Egyetemi Oktatokorhaz, Josa Andras Oktatokorhaz, Sebeszeti Osztaly
🇭🇺Nyíregyháza, Hungary
PHI University Clinic for digestive Surgery
🇲🇰Skopje, North Macedonia
University of Szeged, Faculty of Medicine, Dep.of Surgery
🇭🇺Szeged, Hungary
Fejer-County Saint George University Teaching Hospital, Department of Surgery
🇭🇺Székesfehérvár, Hungary
Portiuncula University Hospital
🇮🇪Ballinasloe, Ireland
Our Lady of Lourdes Hospital
🇮🇪Drogheda, Ireland
Connolly Hospital Blanchardstown
🇮🇪Dublin 15, Ireland
Shaare Zedek Medical Center
🇮🇱Jerusalem, Israel
Galilee Medical Center
🇮🇱Nahariya, Israel
Sheba Medical Center
🇮🇱Ramat Gan, Israel
Kaplan Medical Center
🇮🇱Rehovot, Israel
Assaf Harofeh Medical Center
🇮🇱Zerifin, Israel
Ospedale Policlinico San Martino
🇮🇹Genoa, Italy
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
🇮🇹Rome, Italy
IMSP Institutul de Medicina Urgenta
🇲🇩Chisinau, Moldova, Republic of
IMSP Clinical republican Hospital "Timofei Mosneaga"
🇲🇩Chisinau, Moldova, Republic of
IMSP Institutul of Oncologic
🇲🇩Chisinau, Moldova, Republic of
IMSP Spitalul Clinic Republican "Timofei Mosneaga"
🇲🇩Chisinau, Moldova, Republic of
IMSP Spitalul Clinic Municipal "Gheorghe Paladi"
🇲🇩Chisinau, Moldova, Republic of
IMSP Spitalul Clinic Municipal "Sfanta Treime"
🇲🇩Chisinau, Moldova, Republic of
PHI General Hospital "Borka Taleski" Prilep
🇲🇰Prilep, North Macedonia
PHI University Clinic for Surgical Diseases "st.Naum Ohridski - Skopje"
🇲🇰Skopje, North Macedonia
HD Research LLC / Memorial Hermann Southeast Hospital
🇺🇸Houston, Texas, United States
PHI Clinical Hospital - Shtip
🇲🇰Skopje, North Macedonia
PHI General Hospital - Strumica
🇲🇰Strumica, North Macedonia
Szpital Powiatowy im. Marii Skłodowskiej - Curie w Ostrowie Mazowieckiej SPZZOZ
🇵🇱Ostrów Mazowiecka, Poland
Wojewodzki Szpital Specjalistyczny we Wroclawiu
🇵🇱Wrocław, Poland
Centrum Medyczne Med-Gastr
🇵🇱Łódź, Poland
Unidade Local de Saúde da Região de Aveiro E. P. E.
🇵🇹Aveiro, Portugal
Centro Clinico Academico de Braga Associação - Hospital de Braga
🇵🇹Braga, Portugal
Unidade de Saúde Local da Guarda
🇵🇹Guarda, Portugal
Sf. Constantin Hospital
🇷🇴Braşov, Romania
Spitalul Clinic Judetean de Urgenta Craiova, Sectia Cbirurgie Generala II
🇷🇴Craiova, Romania
Spitalul Clinic Judetean de Urgenta Craiova, Sectia Chirurgie Generala III
🇷🇴Craiova, Romania
Spitalul Clinic JudeIean de Urgenta "Pius Brinzeu", Sectia Chirurgie Generala II
🇷🇴Timisoara, Romania
Mures County Clinical Hospital
🇷🇴Târgu-Mureş, Romania
UCC Zvezdara
🇷🇸Belgrade, Serbia
UCC Nis
🇷🇸Nis, Serbia
Oncology Institute of Vojvodina
🇷🇸Sremska Kamenica, Serbia
Health Center Valjevo
🇷🇸Valjevo, Serbia
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Baylor University Medical Center
🇺🇸Dallas, Texas, United States
Bács-Kiskun Megyei Kórház
🇭🇺Kecskemét, Hungary
Szent Borbála Kórház
🇭🇺Tatabánya, Hungary
Soroka Medical Center
🇮🇱Be'er Sheva, Israel
Bnai Zion Medical Center
🇮🇱Haifa, Israel
Carmel Medical Center
🇮🇱Haifa, Israel
Clinical Centre Kragujevac, General and Thoracic Surgery Clinic
🇷🇸Kragujevac, Serbia