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

Sponsor

PolyPid Ltd. (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04233424

Collaborator

(none)

950

Enrollment

Locations

Arms

26.3

Anticipated Duration (Months)

16.1

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Surgical Site Infection Colon Surgery Abdominal Surgery Post-Op Infection	Drug: D-PLEX Other: Standard of Care (SoC)	Phase 3

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

Study Design

Study Type:

Interventional

Actual Enrollment :

950 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

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.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.

Masking:

Triple (Participant, Care Provider, Investigator)

Masking Description:

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.

Primary Purpose:

Prevention

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)

Actual Study Start Date :

Jun 24, 2020

Anticipated Primary Completion Date :

Aug 2, 2022

Anticipated Study Completion Date :

Sep 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: D-PLEX+SoC D-PLEX is provided to suitable and willing study subjects as an adjunct to the SoC treatment	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 β Tri-Calcium polymer and a lipid matrix. All formulation components are biodegradable.
Other: Standard of care The SoC for prophylactic antibiotic treatment is based on international guidelines	Other: Standard of Care (SoC) prophylactic, pre-operation per institution guidelines

Arm

Intervention/Treatment

Experimental: D-PLEX+SoC

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

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 β Tri-Calcium polymer and a lipid matrix. All formulation components are biodegradable.

Other: Standard of care

The SoC for prophylactic antibiotic treatment is based on international guidelines

Other: Standard of Care (SoC)

prophylactic, pre-operation per institution guidelines

Outcome Measures

Primary Outcome Measures

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)].

Secondary Outcome Measures

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, 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)].

Other Outcome Measures

Assess Safety of D-PLEX in Prevention of Post Abdominal Surgery Incisional [By day 60 post surgery]
Safety parameters will be evaluated by adverse events
All-cause mortality and re-interventions in the target incision due to SSI [By day 30 post surgery]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

INCLUSION CRITERIA:

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).
Subjects are preoperative hemodynamically stable
Male or non-pregnant female.
Female of child-bearing potential should have a negative pregnancy test 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

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.)
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 abdominal surgery, including concomitant repair of ventral hernia. Salpingo-oophorectomy and cholecystectomy are allowed.
Subjects who received any anti-cancer treatment within the last 4 weeks of surgery.
Subjects who received radiation for colorectal cancer to the abdomen area, prior to 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.
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.
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.
Subjects with other concurrent severe and/or uncontrolled medical conditions.
Psychiatric or any other disorder that compromises ability to provide informed consent for participation in this study.
Chronic alcoholic or drug abuse subjects.
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.
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.
Subjects participating in any other interventional study.
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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Shoals Medical Trials	Sheffield	Alabama	United States	35660
2	Cedars-Sinai Medical Center	Los Angeles	California	United States	90048
3	Paradigm Clinical Research Center	Redding	California	United States	96001
4	Tufts Medical Center	Boston	Massachusetts	United States	02111
5	Siteman Cancer Center - South County	Saint Louis	Missouri	United States	63110
6	Summit Medical Group	Bend	Oregon	United States	97701
7	"Multiprofile Hospital for Active Treatment - Blagoevgrad" AD	Blagoevgrad		Bulgaria	2700
8	"Multiprofile Hospital for Active Treatment "Sveti Ivan Rilski - 2003" OOD	Dupnitsa		Bulgaria	2600
9	"Multiprofile Hospital for Active Treatment St. Ivan Rilski Gorna Oryahovitsa" EOOD	Gorna Oryahovitsa		Bulgaria	5100
10	"Multiprofile Hospital for Active Treatment - Haskovo" AD	Haskovo		Bulgaria	6304
11	"Multiprofile Hospital for Active Treatment - Uni Hospital" OOD	Panagyurishte		Bulgaria	4500
12	"MHAT "Rahila Angelova"" AD	Pernik		Bulgaria	2300
13	"MHAT Sveta Caridad" EAD	Plovdiv		Bulgaria	4004
14	"Multiprofile hospital for active treatment - Plovdiv" AD	Plovdiv		Bulgaria	4027
15	University First Multiprofile Hospital for Active Treatment - Sofia	Sofia		Bulgaria	1154
16	"IV Multiprofile Hospital for Active Treatment - Sofia" EAD	Sofia		Bulgaria	1606
17	"University Multiprofile Hospital for Active Treatment and Emergency Medicine N. I. Pirogov" EAD	Sofia		Bulgaria	1606
18	"Multiprofile Regional Hospital for Active Treatment "Dr. St. Cherkezov"" AD	Veliko Tarnovo		Bulgaria	5002
19	Complex Oncology Center - Vratsa - EOOD	Vratsa		Bulgaria	3000
20	Multiprofile Hospital for Active Treatment	Vratsa		Bulgaria	3001
21	"Multiprofile Hospital for Active Treatment "Sveti Panteleymon"-Yambol AD	Yambol		Bulgaria	8600
22	KBC Rijeka	Rijeka		Croatia	51000
23	General Hospital Zadar	Zadar		Croatia	23000
24	KBC Sestre milosrdnice	Zagreb		Croatia	10000
25	University Hospital Centre Zagreb	Zagreb		Croatia	10000
26	Fakultní Nemocnice Brno	Brno		Czechia	62500
27	Krajská nemocnice Liberec	Liberec		Czechia	46001
28	Fakultní Nemocnice Královské Vinohrady	Prague		Czechia	100 34
29	Nemocnice Na Bulovce	Prague		Czechia	18081
30	Ustredni Vojenska Nemocnice Praha	Praha		Czechia	169 02
31	Bajai Szent Rókus Kórház, Sebészeti Osztály	Baja	Bács-Kiskun Megye	Hungary	6500
32	Békés-Megyei Központi Kórház, I. Sebészeti Osztály	Gyula		Hungary	5600
33	Csongrád-Csanád Megyei Egészségügyi Ellátó Központ Hódmezővásárhely - Makó	Hódmezővásárhely		Hungary	6800
34	Somogy Megyei Kaposi Mór Oktató Kórház, Sebészeti Osztály	Kaposvár		Hungary	7400
35	Orosházi Kórház, Invazív Mátrix Sebészet	Orosháza		Hungary	5900
36	Pécsi Tudományegyetem, Klinikai Központ, Sebészeti Klinika	Pécs		Hungary	7624
37	Fejér Megyei Szent György Egyetemi Oktató Kórház, Sebészeti Osztály	Székesfehérvár		Hungary	8000
38	Sheba Medical Center	Ramat Gan	Derech Sheba 2	Israel
39	West Galilee medical Center	Nahariya	Nahariya-Cabri	Israel	22100
40	Kaplan Medical Center	Reẖovot	Pasternak Saint	Israel	76100
41	Rabin Medical Center	Pethah Tiqvā		Israel
42	Assuta Medical center	Tel Aviv		Israel
43	Sourasky Medical Center	Tel Aviv		Israel
44	Shamir Medical Center	Zrifin		Israel
45	IMSP Institut of Emmergency Medicine	Chisinau		Moldova, Republic of	2004
46	IMSP Clinical republican Hospital "Timofei Mosneaga"	Chisinau		Moldova, Republic of	2025
47	IMSP Intitute of Oncology	Chisinau		Moldova, Republic of	2025
48	IMSP Municipal Clinical Hospital "Sfanta Treime"	Chisinau		Moldova, Republic of	2068
49	"Sf. Constantin" Hospital	Brasov		Romania	500388
50	Emergency University Hospital Elias, Clinical Department of General Surgery	Bucharest		Romania	11461
51	Coltea Clinical Hospital	Bucharest		Romania	30171
52	Clinical County Hospital Cluj Napoca	Cluj-Napoca		Romania	400006
53	"Prof. Dr. Octavian Fodor"	Cluj-Napoca		Romania	400162
54	Medical Center Dr.Ianosi, Department of Surgery	Craiova		Romania	200061
55	County Emergency Clinical Hospital Craiova, Department of General Surgery II	Craiova		Romania	200642
56	Spitalul Clinic Judetean de Urgentã Craiova	Craiova		Romania	200642
57	Spitalul Clinic Judetean de Urgentã Targu-Mures	Craiova		Romania	200642
58	Pelican Hospital Oradea	Oradea		Romania	410469
59	County Emergency Clinical Hospital Timisoara "Pius Brînzeu"	Timisoara		Romania	300723