D-PLEX 312 - Safety and Efficacy of D-PLEX in the Prevention of Post Abdominal Surgery Incisional Infection (SHIELD II)

NCT04411199 | Completed Phase 3 DMC FDA Drug

• 1 other identifier: D-PLEX 312
• Study Type: interventional
• Target: 800
• Locations: 13 countries
• Sites: 58

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.

Conditions

Surgical Site Infection; Colon Surgery; Abdominal Surgery; Post-Op Infection

Keywords

Surgical site infection; Abdominal surgery; Colon and small bowl surgery

Outcome Measures

Primary Outcomes (3)

• 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.

  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. \[abdominal incisional infection is defined as Deep Incisional Surgical Site Infection (DSSI) and/or Superficial Incisional Surgical Site Infection (SSSI)\].

  By day 30 post surgery

• Safety of D-PLEX in Prevention of Post Abdominal Surgery

  Safety parameters will be evaluated by adverse events

  By day 60 post surgery

• Safety of D-PLEX in Prevention of Post Abdominal Surgery Incisional

  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

  By day 60 post surgery

Secondary Outcomes (1)

• Assessment of Infection rate in patient undergoing abdominal colon surgery

  At study visits: day 1, day 5, day 14 and day 30 post surgery

Study Arms (2)

D-PLEX+SoC

EXPERIMENTAL

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

Drug: D-PLEX; Other: Standard of Care (SoC)

Standard of Care

OTHER

The SoC for prophylactic antibiotic treatment is based on international guidelines

Other: Standard of Care (SoC)

Interventions

D-PLEX DRUG

D-PLEX is a new formulation of extended release of Doxycycline. Each 5g D-PLEX vial contains 54.6mg Doxycycline free base (1.09%), which is equivalent to 63mg Doxycycline hyclate (1.26%). D-PLEX is supplied as a sterile powder to be reconstituted to paste in the operating room, using standard aseptic techniques and is intended for single administration. The non-active components of the extended release antibiotic formulation are β Tri-Calcium polymer and a lipid matrix. All formulation components are biodegradable.

D-PLEX+SoC

Standard of Care (SoC) OTHER

prophylactic, pre-operation per institution guidelines

D-PLEX+SoC; Standard of Care

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.)
• Subjects who underwent an intra-abdominal surgery within the last 6 months prior to randomization.
• 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.
• 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 .
• Subjects who received any anti-cancer treatment within the last 4 weeks of surgery.
• Subjects who received radiation for colorectal cancer to the abdomen and/or pelvis area, within the last 4 weeks of the planned abdominal surgery.
• Subjects who received oral or IV Doxycycline or Tetracycline family antibiotics during the past 4 weeks prior to randomization.
• Subjects with known allergy 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 completed during the screening process).
• 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.
• Subjects with End Stage Renal Disease (ESRD/ CKD stage 5).
• Subjects with severe hepatic impairment.
• Subjects with chronic urticaria.
• Subjects diagnosed with CVA within the past 6 months prior to randomization.

Sponsors & Collaborators

• PolyPid Ltd.: lead

Study Sites (58)

Augusta Univeristy

Augusta, Georgia, 30912, United States

Location

Ochsner Medical Center

New Orleans, Louisiana, 70121, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Penn State Health Milton S Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

University Clinical Centre of the Republic of Srpska

Banja Luka, 78000, Bosnia and Herzegovina

Location

University Clinical Center Tuzla

Tuzla, 75000, Bosnia and Herzegovina

Location

Cantonal Hospital Zenica

Zenica, 72000, Bosnia and Herzegovina

Location

LLC American Hospital Network

Tbilisi, 0102, Georgia

Location

LTD "Israeli - Georgian Medical Research Clinic Healthycore"

Tbilisi, 0112, Georgia

Location

LTD New Hospitals

Tbilisi, 0114, Georgia

Location

LTD Multiprofile Clinic Consillium Medulla

Tbilisi, 0186, Georgia

Location

University Hospital Erlangen

Erlangen, 91054, Germany

Location

University of Muenster

Münster, 48149, Germany

Location

Bajai Szent Rokus Korhaz, Sebeszeti Osztaly

Baja, 6500, Hungary

Location

Uzsoki Utcai Kórház, Sebészeti Osztály

Budapest, 1145, Hungary

Location

Heves Varmegyei Markhot Ferenc Oktatokorhaz es Rendelointezet Sebeszeti es Ersebeszeti osztaly

Eger, 3300, Hungary

Location

Bugát Pál Kórház, Gasztroenterológia - Sebészet

Gyöngyös, 3200, Hungary

Location

Bács-Kiskun Megyei Kórház

Kecskemét, 6000, Hungary

Location

Pest Megyei Flór Ferenc Kórház Sebészeti Osztály

Kistarcsa, 2143, Hungary

Location

Szabolcs-Szatmar-Bereg Varmegyei Korhazak es Egyetemi Oktatokorhaz, Josa Andras Oktatokorhaz, Sebeszeti Osztaly

Nyíregyháza, 4400, Hungary

Location

University of Szeged, Faculty of Medicine, Dep.of Surgery

Szeged, 6725, Hungary

Location

Fejer-County Saint George University Teaching Hospital, Department of Surgery

Székesfehérvár, 8000, Hungary

Location

Our Lady of Lourdes Hospital

Drogheda, A92 VW28, Ireland

Location

Soroka Medical Center

Beersheba, 8457108, Israel

Location

Bnai Zion Medical Center

Haifa, 3339419, Israel

Location

Carmel Medical Center

Haifa, 3436212, Israel

Location

Shaare Zedek Medical Center

Jerusalem, 9372212, Israel

Location

Galilee Medical Center

Nahariya, 2210001, Israel

Location

Sheba Medical Center

Ramat Gan, 5262000, Israel

Location

Kaplan Medical Center

Rehovot, 7661041, Israel

Location

Assaf Harofeh Medical Center

Ẕerifin, 70300, Israel

Location

IMSP Institutul de Medicina Urgenta

Chisinau, MD2004, Moldova

Location

IMSP Clinical republican Hospital "Timofei Mosneaga"

Chisinau, MD2025, Moldova

Location

IMSP Institutul of Oncologic

Chisinau, MD2025, Moldova

Location

IMSP Spitalul Clinic Republican "Timofei Mosneaga"

Chisinau, MD2025, Moldova

Location

IMSP Spitalul Clinic Municipal "Gheorghe Paladi"

Chisinau, MD2038, Moldova

Location

IMSP Spitalul Clinic Municipal "Sfanta Treime"

Chisinau, MD2068, Moldova

Location

PHI General Hospital "Borka Taleski" Prilep

Prilep, 7500, North Macedonia

Location

PHI University Clinic for digestive Surgery

Skopje, 1000, North Macedonia

Location

PHI University Clinic for Surgical Diseases "st.Naum Ohridski - Skopje"

Skopje, 1000, North Macedonia

Location

PHI Clinical Hospital - Shtip

Skopje, 2000, North Macedonia

Location

PHI General Hospital - Strumica

Strumica, 2400, North Macedonia

Location

Centrum Medyczne Med-Gastr

Lodz, 91-034, Poland

Location

Szpital Powiatowy im. Marii Skłodowskiej - Curie w Ostrowie Mazowieckiej SPZZOZ

Ostrów Mazowiecka, 07-300, Poland

Location

Unidade Local de Saúde da Região de Aveiro E. P. E.

Aveiro, 3810-164, Portugal

Location

Centro Clinico Academico de Braga Associação - Hospital de Braga

Braga, 4710-243, Portugal

Location

Unidade de Saúde Local da Guarda

Guarda, 6300-749, Portugal

Location

Sf. Constantin Hospital

Brasov, 500388, Romania

Location

Spitalul Clinic Judetean de Urgenta Craiova, Sectia Cbirurgie Generala II

Craiova, 200642, Romania

Location

Spitalul Clinic Judetean de Urgenta Craiova, Sectia Chirurgie Generala III

Craiova, 200642, Romania

Location

Mures County Clinical Hospital

Târgu Mureş, 540103, Romania

Location

Spitalul Clinic JudeIean de Urgenta "Pius Brinzeu", Sectia Chirurgie Generala II

Timișoara, 300723, Romania

Location

First Surgical Clinic

Belgrade, 11000, Serbia

Location

Oncology Institute of Vojvodina

Kamenitz, 21204, Serbia

Location

UCC Nis

Niš, 18000, Serbia

Location

General Hospital Sremska Mitrovica

Sremska Mitrovica, 22000, Serbia

Location

Health Center Valjevo

Valjevo, 14000, Serbia

Location

MeSH Terms

Conditions

Surgical Wound Infection

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Wound Infection; Infections; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: 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.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: May 27, 2020
• First Posted: June 2, 2020
• Study Start: December 15, 2020
• Primary Completion: April 14, 2025
• Study Completion: May 10, 2025
• Last Updated: June 10, 2025

Record last verified: 2025-06

Locations

HU (9); PL (2); US (5); SE (5); GE (4); RO (5); BO (3); DE (2); MO (6); IL (8); PT (3); IE (1); NO (5)