Clinical trial NCT03558984: D-PLEX 302: Efficacy and Safety of D-PLEX in the Prevention of Sternal Infection Post Cardiac Surgery
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Surgical Site Infection
Sternal Infection
Cardiac Surgery
Keywords: Cardiac
Surgery
Sternotomy
Heart
CABG
Valve-replacement
Aorta-replacement
Lead sponsor: PolyPid Ltd.
Sponsor class: INDUSTRY
First posted: 2018-06-15
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Eligible subjects will be randomized to either the treatment arm (D-PLEX + SOC prophylactic antibiotic treatment) or to control arm (SOC prophylactic antibiotic treatment only), in a 1:1 ratio.

Subjects will be blinded to the study arm.
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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.).

Primary outcomes:
measure: Sternal Wound Infection rate
timeFrame: within 90 days (3 months) post sternotomy for cardiac surgery
Secondary outcomes:
measure: Hospitalization days
timeFrame: 90 days
measure: Average ASEPSIS assessment score
timeFrame: 90 days (3 months) post sternotomy
measure: Number of surgical re-interventions
timeFrame: 90 days (3 months) post sternotomy
measure: Superficial Sternal Wound Infections (SSWI)
timeFrame: 90 days (3 months) post sternotomy
measure: Deep Sternal Wound Infections (DSWI)
timeFrame: 90 days (3 months) post sternotomy
measure: Mortality rate associated with Sternal Wound Infection (SWI)
timeFrame: 90 days (3 months) post sternotomy
measure: Determination of susceptibility to Doxycycline
timeFrame: 90 days (3 months) post sternotomy
Other outcomes:
measure: Overall hospitalization days
timeFrame: 6 months
measure: Readmission due to Sternal Surgical Site Infection
timeFrame: 90 days (3 months) post sternotomy
measure: Time to Sternal Wound Infection
timeFrame: 90 days (3 months) post sternotomy
measure: Analgesic treatment
timeFrame: 6 months
measure: Visual Analogue Score (VAS) assessment
timeFrame: 6 months
measure: Antibiotic treatment due to Sternal Surgical Site Infections (all routes of administration).
timeFrame: 90 days (3 months) post sternotomy
measure: Antibiotic treatment due to Sternal Surgical Site Infections (IV administration).
timeFrame: 90 days (3 months) post sternotomy
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Houston
country: United States
facility: Memorial Hermann
state: Texas
city: Beer Sheva
country: Israel
facility: Soroka Medical Center
Study officials:
affiliation: Mayo Clinic, 220 First Street SW, Rochester, MN. 55902
name: Hartzell V. Schaff, M.D.
role: PRINCIPAL_INVESTIGATOR
References: