Postoperative Wound Infection Deep Incisional Surgical Site, Postoperative Wound Infection Superficial Incisional
Conditions
Keywords
Mediastenitis, prevention of surgical site infection (SSI)
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.
Interventions
DRUGD-PLEX
D-PLEX will be administered as a single application during the open heart surgery (index procedure) immediately prior to sternal closure, as an adjunct to the standard care.
PROCEDUREOpen heart surgery
Subject will undergo open heart surgery according to standard of care
Sponsors
PolyPid Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
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).
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Decrease of Infection Rate as Measured by the Proportion of Subjects With at Least 1 Identified Sternal Infection Within 90 Days Post-cardiac Surgery. | Within 90 days post-cardiac surgery. | The primary endpoint was the decrease in infection rate as measured by the proportion of subjects with at least one identified sternal infection, DSWI (Deep sternal wound infections) and SSWI (Superficial Sternal Wound Infection) within 90 days of post-cardiac surgery. One patient in the Control arm had an SSWI on day 6 post-surgery. The infection was confirmed by a bacteriology test positive for Proteus mirabilis. No subjects in the D-PLEX treatment arm experienced any sternal wound infections and no infection was confirmed during 90 days post-surgery. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Decrease in the Number of Readmissions Due to Sternal Surgical Site Infection | Within 90 days post-cardiac surgery. | No readmissions due to sternal surgical site infections were reported in any treatment arm. |
| Decrease in Number of Surgical Re-interventions Due to Sternal Surgical Site Infection. | Within 90 days post-cardiac surgery. | No surgical re-interventions due to sternal surgical site infections were required in any treatment arm. |
| Time to Sternal Infection Post-cardiac Surgery. | Within 90 days post-cardiac surgery. | Only one subject in the Control arm group had an sternal infection on day 6 post cardiac surgery. |
| Decrease of Sternal Infection Rate, DSWI (Deep Sternal Wound Infections) and SSWI (Superficial Sternal Wound Infection) During the First 30 Days Post Operation. | Within 30 days post operation. | One subject in the Control arm group had a Sternal Infection during the first 30 days after surgery. None of the subjects in the D-PLEX+SOC (Treatment arm) group had any sternal infection during this period. |
| Decrease in the Total Number of Sternal Infections, DSWI (Deep Sternal Wound Infections) and SSWI (Superficial Sternal Wound Infection) Between Day 30 and 3 Months. | Between day 30 and 3 months. | No sternal surgical site infections were reported in any treatment arm between Day 30 and 90 days after the surgery. |
| Decrease in the Number of Hospitalization Days Due to Sternal Surgical Site Infection. | Within 90 days post-cardiac surgery. | No hospitalizations due to sternal surgical site infections were reported during the study. |
Countries
Israel
Contacts
PRINCIPAL_INVESTIGATORErez V. Kachel, MD
Sheba MC
Participant flow
Recruitment details
Subjects who met the eligibility criteria and provided signed informed consent were enrolled in the study. In Part 1 of the study, subjects were treated with D-PLEX concomitantly with SOC (Standard of Care). In Part 2 of the study the subjects were randomized 2:1 to receive D-PLEX concomitantly with SOC or SOC only.
Pre-assignment details
A total of 81 subjects were enrolled in the study as follows: Part 1 Open Label, Single Arm: Twenty (20) subjects were enrolled in Part 1 of the study and treated with D-PLEX concomitantly with SOC (Standard of Care). Part 2 Randomized, Single-blinded: Sixty-one (61) subjects were enrolled in Part 2 of the study and randomized to the D-PLEX + SOC (Standard of Care) treatment arm (40 subjects) or to the SOC (Standard of Care) arm (21 subjects).
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 63.5 years STANDARD_DEVIATION 11.1 |
| BMI | 31.8 kg/m^2 STANDARD_DEVIATION 4.6 |
| 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 | 78 Participants |
| Region of Enrollment Israel | 60 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 60 | 0 / 21 |
| other Total, other adverse events | 48 / 60 | 18 / 21 |
| serious Total, serious adverse events | 22 / 60 | 12 / 21 |
Outcome results
None listed