Cardiac Surgery, Sternal Infection, Surgical Site Infection
Conditions
Keywords
Cardiac, Surgery, Sternotomy, Heart, CABG, Valve-replacement, Aorta-replacement
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.
Interventions
DRUGD-PLEX
D-PLEX is a new formulation of extended release of Doxycycline (active ingredient)
OTHERStandard 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."
Sponsors
PolyPid Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, 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.
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Sternal Wound Infection Event | within 90 days (3 months) post sternotomy for cardiac surgery | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hospitalization Days | within 90 days (3 months) post sternotomy for cardiac surgery | Number of Hospitalization days post sternotomy due to sternal infection. |
| Surgical Re-interventions | 90 days (3 months) post sternotomy | Number of Surgical re-interventions due to sternal surgical site infection. |
| ASEPSIS Assessment Score | 90 days (3 month) post sternotomy | 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. |
Countries
Israel, United States
Contacts
PRINCIPAL_INVESTIGATORHartzell V. Schaff, M.D.
Mayo Clinic, 220 First Street SW, Rochester, MN. 55902
Participant flow
Recruitment details
The trial was early terminated after enrolment of two patients.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 2 Participants |
| Region of Enrollment United States | 2 Participants |
| Sex/Gender, Customized Sex Female | 0 Participants |
| Sex/Gender, Customized Sex Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 1 |
| other Total, other adverse events | 0 / 1 | 1 / 1 |
| serious Total, serious adverse events | 1 / 1 | 0 / 1 |
Outcome results
None listed