Clinical trial NCT04233424: D-PLEX 311: Safety and Efficacy of D-PLEX in the Prevention of Post Abdominal Surgery Incisional Infection
Official title: D-PLEX 311- 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 I)
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: 2020-01-18
Enrollment: 950
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.

The final number of subjects will be determined following a comparative interim analysis for an early efficacy or futility stop or unblinded sample size re-estimation: when about 750 subjects will complete their 30 days (1 month) follow-up and evaluated for primary endpoint.
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 resection, with or without a stoma, that includes at least 1 incision that is \> 10 cm (target incision). Eligible and willing subjects will be randomly allocated into 2 blinded 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 and chemistry well as physicians assessment of the incisional wound.

The final number of subjects will be determined following a comparative interim analysis for an early efficacy or futility stop or unblinded sample size re-estimation: when about 750 subjects will complete their 30 days (1 month) follow-up and evaluated for primary endpoint

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 \> 10cm (target incision).
2. Subjects are preoperative hemodynamically stable
3. Male or non-pregnant female.
4. Female of child-bearing potential should have a negative pregnancy test 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, ect.)
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 abdominal surgery, including concomitant repair of ventral hernia. Salpingo-oophorectomy and cholecystectomy are allowed.
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 area, prior to 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, other than resectable non-metastatic colorectal cancer, that is the reason for the index surgery, or carcinoma in situ (or other cancer "in situ = Stage 0"), or squamous cell carcinoma of the skin, or basal cell carcinoma of the skin, or a malignancy that has not been in complete clinical remission and without maintenance chemo or immunotherapy for at least 3 years.
17. Subjects with other concurrent severe and/or uncontrolled medical conditions.
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
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:
measure: Assess Safety of D-PLEX in Prevention of Post Abdominal Surgery Incisional
timeFrame: By day 60 post surgery
measure: All-cause mortality and re-interventions in the target incision due to SSI
timeFrame: By day 30 post surgery
Locations:
city: Sheffield
country: United States
facility: Shoals Medical Trials
state: Alabama
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Redding
country: United States
facility: Paradigm Clinical Research Center
state: California
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Saint Louis
country: United States
facility: Siteman Cancer Center - South County
state: Missouri
city: Bend
country: United States
facility: Summit Medical Group
state: Oregon
city: Blagoevgrad
country: Bulgaria
facility: "Multiprofile Hospital for Active Treatment - Blagoevgrad" AD
city: Dupnitsa
country: Bulgaria
facility: "Multiprofile Hospital for Active Treatment "Sveti Ivan Rilski - 2003" OOD
city: Gorna Oryahovitsa
country: Bulgaria
facility: "Multiprofile Hospital for Active Treatment St. Ivan Rilski Gorna Oryahovitsa" EOOD
city: Haskovo
country: Bulgaria
facility: "Multiprofile Hospital for Active Treatment - Haskovo" AD
city: Panagyurishte
country: Bulgaria
facility: "Multiprofile Hospital for Active Treatment - Uni Hospital" OOD
city: Pernik
country: Bulgaria
facility: "MHAT "Rahila Angelova"" AD
city: Plovdiv
country: Bulgaria
facility: "MHAT Sveta Caridad" EAD
city: Plovdiv
country: Bulgaria
facility: "Multiprofile hospital for active treatment - Plovdiv" AD
city: Sofia
country: Bulgaria
facility: University First Multiprofile Hospital for Active Treatment - Sofia
city: Sofia
country: Bulgaria
facility: "IV Multiprofile Hospital for Active Treatment - Sofia" EAD
city: Sofia
country: Bulgaria
facility: "University Multiprofile Hospital for Active Treatment and Emergency Medicine N. I. Pirogov" EAD
city: Veliko Tarnovo
country: Bulgaria
facility: "Multiprofile Regional Hospital for Active Treatment "Dr. St. Cherkezov"" AD
city: Vratsa
country: Bulgaria
facility: Complex Oncology Center - Vratsa - EOOD
city: Vratsa
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment
city: Yambol
country: Bulgaria
facility: "Multiprofile Hospital for Active Treatment "Sveti Panteleymon"-Yambol AD
city: Rijeka
country: Croatia
facility: KBC Rijeka
city: Zadar
country: Croatia
facility: General Hospital Zadar
city: Zagreb
country: Croatia
facility: KBC Sestre milosrdnice
city: Zagreb
country: Croatia
facility: University Hospital Centre Zagreb
city: Brno
country: Czechia
facility: Fakultní Nemocnice Brno
city: Liberec
country: Czechia
facility: Krajská nemocnice Liberec
city: Prague
country: Czechia
facility: Fakultní Nemocnice Královské Vinohrady
city: Prague
country: Czechia
facility: Nemocnice Na Bulovce
city: Praha
country: Czechia
facility: Ustredni Vojenska Nemocnice Praha
city: Baja
country: Hungary
facility: Bajai Szent Rókus Kórház, Sebészeti Osztály
state: Bács-Kiskun Megye
city: Gyula
country: Hungary
facility: Békés-Megyei Központi Kórház, I. Sebészeti Osztály
city: Hódmezővásárhely
country: Hungary
facility: Csongrád-Csanád Megyei Egészségügyi Ellátó Központ Hódmezővásárhely - Makó
city: Kaposvár
country: Hungary
facility: Somogy Megyei Kaposi Mór Oktató Kórház, Sebészeti Osztály
city: Orosháza
country: Hungary
facility: Orosházi Kórház, Invazív Mátrix Sebészet
city: Pécs
country: Hungary
facility: Pécsi Tudományegyetem, Klinikai Központ, Sebészeti Klinika
city: Székesfehérvár
country: Hungary
facility: Fejér Megyei Szent György Egyetemi Oktató Kórház, Sebészeti Osztály
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
state: Derech Sheba 2
city: Nahariya
country: Israel
facility: West Galilee medical Center
state: Nahariya-Cabri
city: Reẖovot
country: Israel
facility: Kaplan Medical Center
state: Pasternak Saint
city: Pethah Tiqvā
country: Israel
facility: Rabin Medical Center
city: Tel Aviv
country: Israel
facility: Assuta Medical center
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center
city: Zrifin
country: Israel
facility: Shamir Medical Center
city: Chisinau
country: Moldova, Republic of
facility: IMSP Institut of Emmergency Medicine
city: Chisinau
country: Moldova, Republic of
facility: IMSP Clinical republican Hospital "Timofei Mosneaga"
city: Chisinau
country: Moldova, Republic of
facility: IMSP Intitute of Oncology
city: Chisinau
country: Moldova, Republic of
facility: IMSP Municipal Clinical Hospital "Sfanta Treime"
city: Brasov
country: Romania
facility: "Sf. Constantin" Hospital
city: Bucharest
country: Romania
facility: Emergency University Hospital Elias, Clinical Department of General Surgery
city: Bucharest
country: Romania
facility: Coltea Clinical Hospital
city: Cluj-Napoca
country: Romania
facility: Clinical County Hospital Cluj Napoca
city: Cluj-Napoca
country: Romania
facility: "Prof. Dr. Octavian Fodor"
city: Craiova
country: Romania
facility: Medical Center Dr.Ianosi, Department of Surgery
city: Craiova
country: Romania
facility: County Emergency Clinical Hospital Craiova, Department of General Surgery II
city: Craiova
country: Romania
facility: Spitalul Clinic Judetean de Urgentã Craiova
city: Craiova
country: Romania
facility: Spitalul Clinic Judetean de Urgentã Targu-Mures
city: Oradea
country: Romania
facility: Pelican Hospital Oradea
city: Timisoara
country: Romania
facility: County Emergency Clinical Hospital Timisoara "Pius Brînzeu"
Study officials:
References: