Safety of 1 g and 2 g of Cefazolin in Pediatric Subjects

Phase 4, Open-Label, Single-Dose, Parallel-Group Study to Evaluate the Safety of 1 g of Cefazolin in Pediatric Subjects Weighing 25 to Less Than 60 kg and 2 g of Cefazolin in Pediatric Subjects Weighing at Least 60 kg Scheduled for Surgery

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.

Study Overview

• Status: Terminated
• Conditions: Postoperative Infection
• Intervention / Treatment: Drug: Cefazolin 1 g Infusion; Drug: Cefazolin 2 g Infusion

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.

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Arkansas Children's Research Institute
  • Missouri
    • Columbia, Missouri, United States, 65212
      • University of Missouri Health Care System
  • Texas
    • Dallas, Texas, United States, 75235
      • Children's Medical Center Dallas
    • Houston, Texas, United States, 77030
      • The University of Texas Health Science Center at Houston
  • Virginia
    • Roanoke, Virginia, United States, 24013
      • Carilion Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 17 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: 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.	Drug: Cefazolin 1 g Infusion; 1 g cefazolin infusion for pediatric surgical subjects weighing ≥25 to <60 kg
ACTIVE_COMPARATOR: Cefazolin 2 g Infusion; Pediatric surgical subjects weighing at least 60 kg will receive a single 30-minute infusion of 2 g cefazolin.	Drug: Cefazolin 2 g Infusion; 2 g cefazolin infusion for pediatric surgical subjects weighing at least 60 kg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	8 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 4 hours after start of study drug infusion

Collaborators and Investigators

• Sponsor: B. Braun Medical Inc.

Publications and helpful links

Helpful Links

• Ancef (cefazolin for injection) [package insert]. GlaxoSmithKline. Research Triangle Park (NC); 2004 [cited 2016 Jun 08]
• Cefazolin and Dextrose for Injection [package insert]. B. Braun Medical Inc. Bethlehem [PA]; revised 10/2015

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 20, 2017
• Primary Completion (ACTUAL): July 31, 2019
• Study Completion (ACTUAL): July 31, 2019

Study Registration Dates

• First Submitted: July 25, 2017
• First Submitted That Met QC Criteria: July 25, 2017
• First Posted (ACTUAL): July 27, 2017

Study Record Updates

• Last Update Posted (ACTUAL): July 13, 2020
• Last Update Submitted That Met QC Criteria: June 30, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Anti-Infective Agents; Anti-Bacterial Agents; Cefazolin
• Other Study ID Numbers: HC-G-H-1601

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No