D-PLEX 311: Safety and Efficacy of D-PLEX in the Prevention of Post Abdominal Surgery Incisional Infection

Surgical Site Infection Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04233424
• Other study ID #: D-PLEX 311
• Status: Completed
• Phase: Phase 3
• Start date: June 24, 2020
• Est. completion date: September 2, 2022

Study information

• Verified date: May 2022
• Source: PolyPid Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 950
• Est. completion date: September 2, 2022
• Est. primary completion date: September 2, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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).

Related Conditions & MeSH terms

• Abdominal Surgery
• Colon Surgery
• Communicable Diseases
• Infections
• Post-Op Infection
• Surgical Site Infection
• Surgical Wound Infection

Intervention

Drug:
• D-PLEX
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 ß Tri-Calcium polymer and a lipid matrix. All formulation components are biodegradable.

Other:
• Standard of Care (SoC)
prophylactic, pre-operation per institution guidelines

Locations

Country	Name	City	State
Bulgaria	"Multiprofile Hospital for Active Treatment - Blagoevgrad" AD	Blagoevgrad
Bulgaria	"Multiprofile Hospital for Active Treatment "Sveti Ivan Rilski - 2003" OOD	Dupnitsa
Bulgaria	"Multiprofile Hospital for Active Treatment St. Ivan Rilski Gorna Oryahovitsa" EOOD	Gorna Oryahovitsa
Bulgaria	"Multiprofile Hospital for Active Treatment - Haskovo" AD	Haskovo
Bulgaria	"Multiprofile Hospital for Active Treatment - Uni Hospital" OOD	Panagyurishte
Bulgaria	"MHAT "Rahila Angelova"" AD	Pernik
Bulgaria	"MHAT Sveta Caridad" EAD	Plovdiv
Bulgaria	"Multiprofile hospital for active treatment - Plovdiv" AD	Plovdiv
Bulgaria	"IV Multiprofile Hospital for Active Treatment - Sofia" EAD	Sofia
Bulgaria	"University Multiprofile Hospital for Active Treatment and Emergency Medicine N. I. Pirogov" EAD	Sofia
Bulgaria	University First Multiprofile Hospital for Active Treatment - Sofia	Sofia
Bulgaria	"Multiprofile Regional Hospital for Active Treatment "Dr. St. Cherkezov"" AD	Veliko Tarnovo
Bulgaria	Complex Oncology Center - Vratsa - EOOD	Vratsa
Bulgaria	Multiprofile Hospital for Active Treatment	Vratsa
Bulgaria	"Multiprofile Hospital for Active Treatment "Sveti Panteleymon"-Yambol AD	Yambol
Croatia	KBC Rijeka	Rijeka
Croatia	General Hospital Zadar	Zadar
Croatia	KBC Sestre milosrdnice	Zagreb
Croatia	University Hospital Centre Zagreb	Zagreb
Czechia	Fakultní Nemocnice Brno	Brno
Czechia	Krajská nemocnice Liberec	Liberec
Czechia	Fakultní Nemocnice Královské Vinohrady	Prague
Czechia	Nemocnice Na Bulovce	Prague
Czechia	Ustredni Vojenska Nemocnice Praha	Praha
Hungary	Bajai Szent Rókus Kórház, Sebészeti Osztály	Baja	Bács-Kiskun Megye
Hungary	Békés-Megyei Központi Kórház, I. Sebészeti Osztály	Gyula
Hungary	Csongrád-Csanád Megyei Egészségügyi Ellátó Központ Hódmezovásárhely - Makó	Hódmezovásárhely
Hungary	Somogy Megyei Kaposi Mór Oktató Kórház, Sebészeti Osztály	Kaposvár
Hungary	Orosházi Kórház, Invazív Mátrix Sebészet	Orosháza
Hungary	Pécsi Tudományegyetem, Klinikai Központ, Sebészeti Klinika	Pécs
Hungary	Fejér Megyei Szent György Egyetemi Oktató Kórház, Sebészeti Osztály	Székesfehérvár
Israel	West Galilee medical Center	Nahariya	Nahariya-Cabri
Israel	Rabin Medical Center	Pethah Tiqva
Israel	Sheba Medical Center	Ramat Gan	Derech Sheba 2
Israel	Kaplan Medical Center	Re?ovot	Pasternak Saint
Israel	Assuta Medical center	Tel Aviv
Israel	Sourasky Medical Center	Tel Aviv
Israel	Shamir Medical Center	Zrifin
Moldova, Republic of	IMSP Clinical republican Hospital "Timofei Mosneaga"	Chisinau
Moldova, Republic of	IMSP Institut of Emmergency Medicine	Chisinau
Moldova, Republic of	IMSP Intitute of Oncology	Chisinau
Moldova, Republic of	IMSP Municipal Clinical Hospital "Sfanta Treime"	Chisinau
Romania	"Sf. Constantin" Hospital	Brasov
Romania	Coltea Clinical Hospital	Bucharest
Romania	Emergency University Hospital Elias, Clinical Department of General Surgery	Bucharest
Romania	"Prof. Dr. Octavian Fodor"	Cluj-Napoca
Romania	Clinical County Hospital Cluj Napoca	Cluj-Napoca
Romania	County Emergency Clinical Hospital Craiova, Department of General Surgery II	Craiova
Romania	Medical Center Dr.Ianosi, Department of Surgery	Craiova
Romania	Spitalul Clinic Judetean de Urgentã Craiova	Craiova
Romania	Spitalul Clinic Judetean de Urgentã Targu-Mures	Craiova
Romania	Pelican Hospital Oradea	Oradea
Romania	County Emergency Clinical Hospital Timisoara "Pius Brînzeu"	Timisoara
United States	Summit Medical Group	Bend	Oregon
United States	Tufts Medical Center	Boston	Massachusetts
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Paradigm Clinical Research Center	Redding	California
United States	Siteman Cancer Center - South County	Saint Louis	Missouri
United States	Shoals Medical Trials	Sheffield	Alabama

Sponsors (1)

Lead Sponsor	Collaborator
PolyPid Ltd.

Countries where clinical trial is conducted

United States,  Bulgaria,  Croatia,  Czechia,  Hungary,  Israel,  Moldova, Republic of,  Romania, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Assess Safety of D-PLEX in Prevention of Post Abdominal Surgery Incisional	Safety parameters will be evaluated by adverse events	By day 60 post surgery
Other	All-cause mortality and re-interventions in the target incision due to SSI	All-cause mortality and re-intervention at the primary incision site (target) due to suspected SSI or due to poor wound healing, including wound dehiscence (as verified by the blinded adjudication committee), within 30 days post index surgery will be analysed as treatment failure.	By day 30 post surgery
Primary	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)].	By day 30 post surgery
Secondary	Assessment of Infection rate in patient undergoing abdominal colon 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)].	At study visits: day 1, day 5, day 14 and day 30 post surgery