D-PLEX 302: Efficacy and Safety of D-PLEX in the Prevention of Sternal Infection Post Cardiac Surgery

Prospective, Multicenter, Randomized, Parallel Controlled, Two Arms, Single Blind, Study to Assess the Efficacy and Safety of D-PLEX Administered Concomitantly With the SOC IV Prophylactic Antibiotic Treatment vs. SOC in Prevention of Post-Cardiac Surgery Sternal Infections

Prospective, Multinational, Multicenter, Randomized, Parallel Controlled, Two arms, Single Blind, Study to Assess the Efficacy and Safety of D-PLEX Administered Concomitantly with the Standard of Care (SOC) IV Prophylactic Antibiotic Treatment vs. SOC in Prevention of Post-Cardiac Surgery Sternal Infections.

Study to assess D-PLEX efficacy and safety in preventing sternal infections over a period of 90 days (3 months) post cardiac surgery with median sternotomy, in patients with high risk for infection compared to the control arm.

Study Overview

• Status: Terminated
• Conditions: Cardiac Surgery; Surgical Site Infection; Sternal Infection
• Intervention / Treatment: Drug: D-PLEX; Other: Standard of Care

Detailed Description

This is Phase III study to evaluate the anti-infective efficacy and safety of D-PLEX, a new formulation of extended release of Doxycycline, over a period of 3 months post operation by preventing sternal infection post cardiac surgery in patients above the age of 18, including high risk patients for infection. Study will be conducted in about 45 sites in US (about 15 sites), Europe and Israel, recruitment period will last about 18 months. D-PLEX will be administered as a single application. For subjects randomized to the investigational treatment arm, D-PLEX treatment will be applied at the end of the index surgery just before closing the chest, as an adjunct to the SOC prophylactic antibiotic treatment. For subjects randomized to the control arm, the surgical treatment will be as per the SOC. Pre- and post-operative care for both arms will be performed per site SOC. Patients will followed-up during 6 months after surgery.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 3

Contacts and Locations

Study Locations

• Israel
  • Beersheba, Israel
    • Soroka Medical Center
• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55902
      • Mayo Clinic
  • Texas
    • Huston, Texas, United States, 77024
      • Memorial Hermann

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Subjects scheduled to elective and/or urgent median sternotomy for cardiac surgery, who are preoperative hemodynamically stable.
2. Males and females.
3. Subjects age of 18 and older.

4. Subjects with both Diabetes Mellitus AND BMI≥30 OR

   Diabetes Mellitus/BMI≥30 AND at least one of the following:

   • Current/Previous smoking history ≥30 pack year
   • Chronic Obstructive Pulmonary Disease (COPD)

5. Female of childbearing potential should have a negative serum pregnancy test prior to index procedure.

   Note: All female of childbearing potential must agree to use a highly effective method of contraception (such as double barrier, oral or parenteral hormonal, intrauterine device and spermicide) consistently and correctly for the duration of the study.

6. Subject is willing and able to provide a signed Informed Consent Form and is willing and able to comply with study's procedures including follow-up visits.

Exclusion Criteria:

1. Subjects undergoing partial sternotomy.
2. Subjects with any preoperative active significant infection.
3. Subjects that received oral or IV doxycycline during the last 4 weeks prior to screening.
4. Subjects with sensitivity to doxycycline and/or to tetracycline family of drugs and/or other study drug ingredients.
5. Subjects with known allergies to more than 3 substances. (An allergy questionnaire will be filled during the screening process).
6. Subjects with history of allergic/hypersensitivity reaction to any substance having required hospitalization and/or treatment with intra-venous steroids/epinephrine or in the opinion of the investigator the patient is at high risk of developing severe allergic/hypersensitivity reactions.
7. Subjects with uncontrolled Asthma (GINA III-IV).
8. Subjects with chronic urticaria.
9. Immunocompromised subjects from any reason, at screening.
10. Subjects with renal failure requiring dialysis.
11. Subjects scheduled to major organ transplantation and/or to other significant concomitant surgical procedure.
12. Subjects scheduled for mechanical assist device.
13. Subjects scheduled to be treated with preventive negative pressure devices.
14. Subjects undergone Cerebro-Vascular Accident (CVA)/Transient Ischemic Attack (TIA) within the past 3 months prior to randomization.
15. Subjects that have undergone previously, any cardiac surgery through sternotomy.
16. Subjects with active or previous malignancy in the chest area.
17. Any subject with active malignancy or with malignancy that has not been in complete remission for at least 5 years. Subjects who have had carcinoma in situ of the cervix, squamous cell carcinoma of the skin and basal cell carcinoma of the skin, are eligible.
18. Pregnant or breast-feeding women or women of childbearing age not protected by an effective contraceptive method of birth control (such as double barrier, oral or parenteral hormonal, intrauterine device and spermicide).
19. Subjects enrolled in any intervention study with an investigational medicinal product and/or received any investigational medicinal product within 30 days or 5½ half-lives of the product prior to enrollment (whichever is longer).
20. In the opinion of investigator, subject is not eligible to participate in the study and/or to comply with protocol requirements (e.g. due to a cognitive, medical condition or residency distanced from site that may jeopardize Follow-Up visits attendance etc.).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: D-PLEX + SOC; For subjects randomized to the investigational treatment arm, D-PLEX treatment will be applied at the end of the index surgery just before closing the chest, as an adjunct to the SOC prophylactic antibiotic treatment.	Drug: D-PLEX; D-PLEX is a new formulation of extended release of Doxycycline (active ingredient); Other: Standard of Care; The SOC prophylactic antibiotic treatment will be consistent and standardized for all sites in the clinical study. is based on "The society of thoracic surgeons practice guideline series: antibiotic prophylaxis in cardiac surgery, part II: antibiotic choice."
Other: Standard of Care; For subjects randomized to the control arm, the surgical treatment will be as per the SOC.	Other: Standard of Care; The SOC prophylactic antibiotic treatment will be consistent and standardized for all sites in the clinical study. is based on "The society of thoracic surgeons practice guideline series: antibiotic prophylaxis in cardiac surgery, part II: antibiotic choice."

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With a Sternal Wound Infection Event	Sternal infection will be identified by predefined criteria based on modification of the CDC's Criteria for Surgical Site Infection (SSI) & Surveillance Definition for Specific Types of Infections Chapters, January 2018	within 90 days (3 months) post sternotomy for cardiac surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospitalization Days	Number of Hospitalization days post sternotomy due to sternal infection.	within 90 days (3 months) post sternotomy for cardiac surgery
Surgical Re-interventions	Number of Surgical re-interventions due to sternal surgical site infection.	90 days (3 months) post sternotomy
ASEPSIS Assessment Score	ASEPSIS is acronym of wound assessment and treatment parameters, which provides numerically score during an inspection of the surgical site. The final score is being interpreted to severity of wound appearance and the clinical consequences of the infection. Parameters and Scores: Serous discharge & Erythema will be marked between 0 - 5. Purulent exudate & Separation of deep tissue are marked between 0 - 10 - based on the proportion of the wound they affect when 0 is none and either 5 or 10 are for over 80% of the wound. Additional antibiotic treatment, a requirement for pus drainage, isolation of bacteria & stay duration as an inpatient are scored Yes or No. No equals 0. Yes is calculated as either 5 points (for some parameters) or 10 for others. The final score can be in the range of 0 - 70. 0 - 10 for wound which heals satisfactorily and over 40 for a severe wound infection.	90 days (3 month) post sternotomy

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Superficial Sternal Wound Infections (SSWI)	Incidence of Superficial Sternal Wound Infections (SSWI) during 90 days post sternotomy will be analyzed using Fisher's Exact test similarly to the primary end point.	90 days (3 months)
Incidence of Deep Sternal Wound Infection (DSWI)	Incidence of Deep Sternal Wound Infections (DSWI) during 90 days post sternotomy will be analyzed using Fisher's Exact test similarly to the primary end point.	90 days (3 months) post sternotomy
Mortality Rate Associated With Sternal Wound Infection (SWI)	The analysis of Mortality rate associated with Sternal Wound Infection (SWI) within 90 days (3 months) post sternotomy will be analyzed using Fisher's Exact test similarly to the primary end point.	within 90 days (3 month) post sternotomy
Susceptibility to Doxycycline	Determination of susceptibility to Doxycycline of any organism recovered from a Sternal Surgical Site Infection. The number of participants who have bacterial growth analyzed (if any).	up to 90 days post surgery

Collaborators and Investigators

• Sponsor: PolyPid Ltd.
• Investigators: Principal Investigator: Hartzell V. Schaff, M.D., Mayo Clinic, 220 First Street SW, Rochester, MN. 55902

Study record dates

Study Major Dates

• Study Start (Actual): December 17, 2019
• Primary Completion (Actual): October 24, 2022
• Study Completion (Actual): October 24, 2022

Study Registration Dates

• First Submitted: June 5, 2018
• First Submitted That Met QC Criteria: June 14, 2018
• First Posted (Actual): June 15, 2018

Study Record Updates

• Last Update Posted (Actual): June 30, 2026
• Last Update Submitted That Met QC Criteria: June 23, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Surgery; CABG; Heart; Cardiac; Sternotomy; Valve-replacement; Aorta-replacement
• Additional Relevant MeSH Terms: Postoperative Complications; Pathologic Processes; Infections; Wound Infection; Pathological Conditions, Signs and Symptoms; Surgical Wound Infection; Health Services Administration; Health Care Quality, Access, and Evaluation; Quality of Health Care; Quality Indicators, Health Care; Standard of Care
• Other Study ID Numbers: D-PLEX 302

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No