Postoperative Infection
Conditions
Brief summary
This is a Phase 4, open-label, single-dose, parallel-group, multicenter, safety study of cefazolin (1 g or 2 g) in pediatric subjects between 10 and 17 years of age (inclusive) scheduled for surgery.
Detailed description
Approximately 110 subjects will be enrolled and assigned to 1 of the 2 dose groups in a 1:1 ratio (55 subjects in each group). Subjects with a weight of at least 25 kg but less than 60 kg will receive a single IV dose of 1 g cefazolin. Subjects with a weight of at least 60 kg will receive a single IV dose of 2 g cefazolin. Dose groups will not be balanced by age or gender. Additional subjects may be enrolled if necessary to ensure at least 50 evaluable subjects with complete safety data per dose group complete the study. In a subset of approximately 40 subjects, 4 PK samples will be obtained to determine the cefazolin plasma concentrations in this population.
Interventions
DRUGCefazolin 1 g Infusion
1 g cefazolin infusion for pediatric surgical subjects weighing ≥25 to \<60 kg
2 g cefazolin infusion for pediatric surgical subjects weighing at least 60 kg
Sponsors
B. Braun Medical Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Masking description
n/a, this is an open label study
Intervention model description
Approximately 110 subjects will be enrolled and assigned to 1 of the 2 dose groups in a 1:1 ratio (55 subjects in each group). Subjects with a weight of at least 25 kg but less than 60 kg will receive a single IV dose of 1 g cefazolin. Subjects with a weight of at least 60 kg will receive a single IV dose of 2 g cefazolin. Dose groups will not be balanced by age or gender.
Eligibility
Sex/Gender
ALL
Age
10 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
1. The subject is between the ages of 10 and 17 years (inclusive) at the time of giving informed consent. 2. The subject is scheduled for surgery that will last less than 3 hours. 3. The subject and the subject's legally authorized representative voluntarily agree that the subject will participate in this study. In accordance with applicable laws, regulations, and institutional review board requirements, the subject signs or orally agrees to an age-appropriate assent and the subject's legally authorized representative signs both an institutional review board approved informed consent form and Health Insurance Portability and Accountability Act authorization prior to the performance of any screening procedures. 4. For subjects who agree to participate in the PK subgroup additional consent will be obtained. 5. The subject weighs (on Day 1) ≥25 kg but \<60 kg for inclusion in 1 g dose group. 6. The subject weighs (on Day 1) ≥60 kg for inclusion in 2 g dose group. 7. The subject has been scheduled for any type of surgery requiring single dose perioperative cefazolin prophylaxis.
Exclusion criteria
1. Female subjects who are pregnant or lactating/breastfeeding. 2. Female subjects of childbearing potential who are sexually active and who are not willing to use an effective method of birth control during the study period, eg, oral contraceptives, double barrier methods, hormonal injectable or implanted contraceptives, tubal ligation, or have a partner with a vasectomy. 3. The subject has impaired renal function based on the revised Schwartz formula. 4. The subject has a known allergy or hypersensitivity to β lactam/cephalosporin antibiotics, penicillins, corn products, or dextrose containing products or solutions, or any of the other ingredients of Cefazolin for Injection United States Pharmacopeia (USP) and Dextrose Injection USP in DUPLEX. 5. The subject has abnormal vital signs or an abnormal electrocardiograph (ECG) considered by the investigator to be clinically significant. 6. The subject has a result of any laboratory test (or repeat test, if done), obtained as standard of care, that is outside the normal limit of the site's laboratory reference range AND is considered by the investigator to be clinically significant. 7. The subject has a known history of human immunodeficiency virus, hepatitis B, or hepatitis C infection. 8. The subject has a history of alcohol or drug abuse. 9. The subject has received any other investigational drug/device within 30 days prior to the study drug administration. 10. The subject has a history of or is currently smoking or using nicotine-containing substances or electronic cigarettes as determined by medical history or subject's verbal report.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events [Safety] | 8 days | Safety will be assessed by monitoring adverse events (AEs), physical examinations, vital signs, ECGs, and clinical laboratory results. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cefazolin Plasma Concentration Following Infusion | Up to 4 hours after start of study drug infusion | Concentrations will be determined through analysis of 4 blood samples drawn at 0.5-1, 2, 3, and 4 hours after the start of study drug infusion. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cefazolin 1 g Infusion Pediatric surgical subjects weighing at least 25 kg to less than 60 kg will receive a single 30-minute infusion of 1 g cefazolin.
Cefazolin 1 g Infusion: 1 g cefazolin infusion for pediatric surgical subjects weighing ≥25 to \<60 kg | 33 |
| Cefazolin 2 g Infusion Pediatric surgical subjects weighing at least 60 kg will receive a single 30-minute infusion of 2 g cefazolin.
Cefazolin 2 g Infusion: 2 g cefazolin infusion for pediatric surgical subjects weighing at least 60 kg | 28 |
| Total | 61 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Physician Decision | 1 | 0 |
Baseline characteristics
| Characteristic | Cefazolin 1 g Infusion | Cefazolin 2 g Infusion | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 33 Participants | 28 Participants | 61 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 4 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 31 Participants | 24 Participants | 55 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 6 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 26 Participants | 20 Participants | 46 Participants |
| Region of Enrollment United States | 33 participants | 28 participants | 61 participants |
| Sex: Female, Male Female | 16 Participants | 16 Participants | 32 Participants |
| Sex: Female, Male Male | 17 Participants | 12 Participants | 29 Participants |
| Weight | 49.68 kg | 81.49 kg | 64.29 kg |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 33 | 0 / 28 |
| other Total, other adverse events | 13 / 33 | 14 / 28 |
| serious Total, serious adverse events | 1 / 33 | 0 / 28 |
Outcome results
Primary
Number of Participants With Treatment-Emergent Adverse Events [Safety]
Safety will be assessed by monitoring adverse events (AEs), physical examinations, vital signs, ECGs, and clinical laboratory results.
Time frame: 8 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cefazolin 1 g Infusion | Number of Participants With Treatment-Emergent Adverse Events [Safety] | 13 Participants |
| Cefazolin 2 g Infusion | Number of Participants With Treatment-Emergent Adverse Events [Safety] | 14 Participants |
Secondary
Cefazolin Plasma Concentration Following Infusion
Concentrations will be determined through analysis of 4 blood samples drawn at 0.5-1, 2, 3, and 4 hours after the start of study drug infusion.
Time frame: Up to 4 hours after start of study drug infusion
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cefazolin 1 g Infusion | Cefazolin Plasma Concentration Following Infusion | 0.5 - 1.0 HR | 124.7 mcg/mL | Standard Deviation 33.88 |
| Cefazolin 1 g Infusion | Cefazolin Plasma Concentration Following Infusion | 2 HR | 53.51 mcg/mL | Standard Deviation 14.399 |
| Cefazolin 1 g Infusion | Cefazolin Plasma Concentration Following Infusion | 3 HR | 37.35 mcg/mL | Standard Deviation 10.273 |
| Cefazolin 1 g Infusion | Cefazolin Plasma Concentration Following Infusion | 4 HR | 27.30 mcg/mL | Standard Deviation 6.0245 |
| Cefazolin 2 g Infusion | Cefazolin Plasma Concentration Following Infusion | 4 HR | 45.03 mcg/mL | Standard Deviation 20.232 |
| Cefazolin 2 g Infusion | Cefazolin Plasma Concentration Following Infusion | 0.5 - 1.0 HR | 145.5 mcg/mL | Standard Deviation 62.116 |
| Cefazolin 2 g Infusion | Cefazolin Plasma Concentration Following Infusion | 3 HR | 57.74 mcg/mL | Standard Deviation 24.106 |
| Cefazolin 2 g Infusion | Cefazolin Plasma Concentration Following Infusion | 2 HR | 93.26 mcg/mL | Standard Deviation 42.267 |