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

Sponsor

PolyPid Ltd. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03558984

Collaborator

(none)

1,600

Enrollment

Locations

Arms

35.5

Anticipated Duration (Months)

533.3

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Surgical Site Infection Sternal Infection Cardiac Surgery	Drug: D-PLEX Other: Standard of Care	Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

1600 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

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.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.

Masking:

Double (Participant, Outcomes Assessor)

Masking Description:

Subjects will be blinded to the treatment arm assignment. The study site personnel present at the baseline procedure as well as the physician performing the procedure will be trained not to disclose the treatment arm to the subject, his/her family, to health care providers outside of the surgery department and to the study sponsor. Two independent of the sponsor/investigator committees will be involved in the assessment of study outcomes.

Primary Purpose:

Prevention

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

Actual Study Start Date :

Dec 17, 2019

Anticipated Primary Completion Date :

Sep 1, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

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."

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

Outcome Measures

Primary Outcome Measures

Sternal Wound Infection rate [within 90 days (3 months) post sternotomy for cardiac surgery]
Infection rate as measured by the proportion of subjects with a sternal wound infection event. Sternal wound infection is composed of Deep Sternal Wound Infection (DSWI) & Superficial Sternal Wound Infection (SSWI). Mortality from any reason within 90 days (3 months) post sternotomy, will be analyzed as treatment failure.

Secondary Outcome Measures

Hospitalization days [90 days]
Average number of Hospitalization days post sternotomy due to sternal infection.
Average ASEPSIS assessment score [90 days (3 months) post sternotomy]
ASEPSIS (Additional treatment, Serous discharge, Erythema, Purulent exudate, Separation of deep tissue, Isolation of bacteria, Stay duration as inpatient), for 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 infections.
Number of surgical re-interventions [90 days (3 months) post sternotomy]
Number of surgical re-intervention due to sternal surgical site infection.
Superficial Sternal Wound Infections (SSWI) [90 days (3 months) post sternotomy]
Incidence of Superficial Sternal Wound Infections (SSWI)
Deep Sternal Wound Infections (DSWI) [90 days (3 months) post sternotomy]
Incidence of Deep Sternal Wound Infections (DSWI)
Mortality rate associated with Sternal Wound Infection (SWI) [90 days (3 months) post sternotomy]
Mortality rate associated with Sternal Wound Infection (SWI)
Determination of susceptibility to Doxycycline [90 days (3 months) post sternotomy]
Determination of susceptibility to Doxycycline of any organism recovered from a Sternal Surgical Site Infection.

Other Outcome Measures

Overall hospitalization days [6 months]
Overall Hospitalization days, for any reason.
Readmission due to Sternal Surgical Site Infection [90 days (3 months) post sternotomy]
Number of readmissions due to Sternal Surgical Site Infection
Time to Sternal Wound Infection [90 days (3 months) post sternotomy]
Time to sternal wound infection (Post Operating Day) post sternotomy.
Analgesic treatment [6 months]
Average number of analgesic treatment days
Visual Analogue Score (VAS) assessment [6 months]
VAS score assessment, self-completed by the respondent, from 0 (no pain) to 10 (worst imaginable pain)
Antibiotic treatment due to Sternal Surgical Site Infections (all routes of administration). [90 days (3 months) post sternotomy]
Average number of Antibiotic Treatment (overall IV and other administration modes, e.g. oral) days due to sternal Surgical Site Infection (SSWI & DSWI)
Antibiotic treatment due to Sternal Surgical Site Infections (IV administration). [90 days (3 months) post sternotomy]
Average number of Antibiotic Treatment (IV administration) days due to sternal Surgical Site Infection (SSWI & DSWI)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

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.

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:

Subjects undergoing partial sternotomy.
Subjects with any preoperative active significant infection.
Subjects that received oral or IV doxycycline during the last 4 weeks prior to screening.
Subjects with sensitivity to doxycycline and/or to tetracycline family of drugs and/or other study drug ingredients.
Subjects with known allergies to more than 3 substances. (An allergy questionnaire will be filled during the screening process).
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.
Subjects with uncontrolled Asthma (GINA III-IV).
Subjects with chronic urticaria.
Immunocompromised subjects from any reason, at screening.
Subjects with renal failure requiring dialysis.
Subjects scheduled to major organ transplantation and/or to other significant concomitant surgical procedure.
Subjects scheduled for mechanical assist device.
Subjects scheduled to be treated with preventive negative pressure devices.
Subjects undergone Cerebro-Vascular Accident (CVA)/Transient Ischemic Attack (TIA) within the past 3 months prior to randomization.
Subjects that have undergone previously, any cardiac surgery through sternotomy.
Subjects with active or previous malignancy in the chest area.
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.
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).
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).
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.).