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

A Phase Ib/II Prospective, Multicenter, Two Part Study; Part 1 - Open Label, Single Arm & Part 2 Randomized, Single-blinded Study to Assess Safety and Efficacy of D-PLEX Concomitantly With Standard of Care vs. Standard of Care Alone in the Prevention of Sternal Infection Post Cardiac Surgery.

This study is aimed to assess the anti-infective efficacy of D-PLEX over a period of 3 months post operation as well as the safety over a period of 6 months, by preventing sternal infection post cardiac surgery in patients above the age of 18, including high risk patients for infection. This study is a 2 parts study: part 1 is a single arm, part 2 is randomized controlled study.

D-PLEX is a new formulation of extended controlled release Doxycycline.

Subjects who meet the eligibility criteria and provide signed informed consent, will be enrolled into the study and will be treated with D-PLEX concomitantly with standard of care.

D-PLEX will be administered as a single application during a cardiac surgery (index procedure) immediately prior to sternal closure, as an adjunct to the standard care.

The study will assess the efficacy and safety of the controlled release antibiotic (doxycycline) by the reduction in the number of sternal infections observed during the treatment period in any subject above the age of 18 years, including patients with high risk for infection.

Additional follow up for prolonged safety assessments only, will be done as follows until 24 weeks.

Inclusion Criteria:

1. Male or non-pregnant female above 18 years old

2. 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.

3. Subjects undergoing elective or urgent cardiac surgery, who are preoperative stable hemodynamically.

4. Subjects with (20≤BMI≤40)

5. Subjects who sign a written informed consent.

Exclusion Criteria:

1. Received any investigational drug within 30 days of start of study or within 5½ half-lives (pharmacokinetic or pharmacodynamics) prior to enrollment (whichever is longer).

2. Are ineligible to receive treatment with:

   • Any preoperative active significant infection
   • Antibiotic sensitivity to Doxycycline and/or tetracycline family of drugs
   • Known allergies to more than 3 substances.(Patients should fill the allergy questioners during the enrolment process)
   • 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.
   • History of uncontrolled Asthma (GINA III-IV)
   • History of chronic urticaria

3. Pregnant or breastfeeding women.

4. Subjects who have taken oral or IV doxycycline during the last 4 weeks prior to screening.

5. Subjects who undergo cardiac/open chest surgeries, which are classified as emergency.

6. Immunocompromised subjects from any reason, at screening.

7. Subjects that undergone TIA/ CVA within the last 3 months prior to enrollment.

8. Subjects that previously underwent any cardiac surgery through mid-sternum.

9. In the opinion of investigator, subject is not eligible to participate in the study due to a cognitive status, medical condition or medication status (other than items listed above)