Clinical trial NCT02731573: Safety and Efficacy of D-PLEX in the Prevention of Sternal Infection Post Cardiac Surgery
Official title: 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 Primary Sternal Infection Post Cardiac Surgery.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Postoperative Wound Infection Superficial Incisional
Postoperative Wound Infection Deep Incisional Surgical Site
Keywords: Mediastenitis
Lead sponsor: PolyPid Ltd.
Sponsor class: INDUSTRY
First posted: 2016-04-07
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase Ib/II, Prospective, Multicenter, Two part study; Part 1 Open Label, Single arm \& Part 2 Randomized, Single-blinded, D-PLEX Concomitantly with Standard Of Care vs. Standard of Care alone.

Study population include subjects above the age of 18 years, that undergoing cardiac surgery through mid-sternotomy, including patients with high risk of infection, such as diabetes (Insulin and/or non-insulin dependent), patients with Peripheral Vascular Disease (PVD), Chronic Obstructive Pulmonary Disease (COPD), heavy smokers, Bilateral Mammary artery harvesting, and subjects administered chronic steroid treatment.

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 (part 1) or randomized 2:1 to D-PLEX concomitantly with standard of care vs. standard of care only (part 2).
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Sternal Infection identified within 90 days post-cardiac surgery. Primary sternal infection as measured by the proportion of subjects with at least 1 identified primary sternal infection within 90 days post-cardiac surgery.
timeFrame: Within 90 days post-cardiac surgery.
Secondary outcomes:
Other outcomes:
Locations:
city: Beer sheva
country: Israel
facility: Soroka Medical Center
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Tel Aviv
country: Israel
facility: Assuta Medical Center
city: Tel Hashomer
country: Israel
facility: Sheba Medical Center
city: Tiberias
country: Israel
facility: Poriya Medical Center
Study officials:
affiliation: Sheba MC
name: Erez Kachel, MD
role: PRINCIPAL_INVESTIGATOR
References: