Study of Ceftriaxone and Benzathine Penicillin G During Pregnancy

Official title

Phase IV Study of the Pharmacokinetics and Safety of Ceftriaxone and Benzathine Penicillin G During Pregnancy

Overview

IMPAACT 2044 is a study to characterize the pharmacokinetics (PK) and safety of ceftriaxone and benzathine penicillin G during pregnancy. Up to 78 pregnant women receiving (1) ceftriaxone for indications other than syphilis or (2) benzathine penicillin G for treatment of syphilis from non-study clinical care providers will be enrolled at study sites located in the United States. Approximately 22 infants of pregnant participants receiving benzathine penicillin G will also be enrolled.

Detailed description

IMPAACT 2044 is a Phase IV, multi-site, open-label, non-randomized, opportunistic study to characterize the pharmacokinetics (PK) and safety of ceftriaxone and benzathine penicillin G during pregnancy.

The study includes two arms, with Arm 1 subdivided by route of administration:

Arm 1A: Intravenous (IV) ceftriaxone Arm 1B: Intramuscular (IM) ceftriaxone Arm 2: IM benzathine penicillin G

Interventions

• Drug Ceftriaxon
  Ceftriaxone will not be provided as part of the study. Pregnant participants will receive these drugs as prescribed outside the study by their non-study clinical care provider
• Drug Benzathine penicillin G
  Benzathine penicillin G will not be provided as part of the study. Pregnant participants will receive these drugs as prescribed outside the study by their non-study clinical care provider

Primary outcome measures

• Geometric mean area under the curve (AUC) during the dosing interval (AUC0-tau) in the first trimester trimester [Time frame: First on-study dose through 24 hours]
• Geometric mean terminal elimination half-life (t1/2) in the first trimester [Time frame: First on-study dose through 24 hours]
• Geometric mean trough concentration (Ctrough) in the first trimester [Time frame: First on-study dose through 24 hours]
• Geometric mean AUC0-tau in the second trimester [Time frame: First on-study dose through 24 hours]
• Geometric mean t1/2 in the second trimester [Time frame: First on-study dose through 24 hours]
• Geometric mean Ctrough in the second trimester [Time frame: First on-study dose through 24 hours]
• Geometric mean AUC0-tau in the third trimester [Time frame: First on-study dose through 24 hours]
• Geometric mean t1/2 in the third trimester [Time frame: First on-study dose through 24 hours]
• Geometric mean Ctrough in the third trimester [Time frame: First on-study dose through 24 hours]
• Median maximum plasma concentration during the dose interval (Cmax) in the first trimester [Time frame: First on-study dose through up to 24 hours]

Secondary outcome measures (9)

• Proportion of participants with a maternal serious adverse event (SAE) [Time frame: First on-study dose through 7 days]
• Proportion of participants with a maternal SAE assessed as related to drug under study [Time frame: First on-study dose through 7 days]
• Proportion of participants with a maternal SAE [Time frame: First on-study dose through up to 28 days]
• Proportion of participants with a maternal SAE assessed as related to drug under study [Time frame: First on-study dose through up to 28 days]
• Proportion of participants with a spontaneous abortion or miscarriage (<20 weeks gestation) [Time frame: At pregnancy outcome/delivery/birth]
• Proportion of participants with a stillbirth (≥20 weeks gestation) [Time frame: At pregnancy outcome/delivery/birth]
• Proportion of participants with an infant small for gestational age (SGA; weight <10th percentile for gestational age, adjusted for sex) [Time frame: At pregnancy outcome/delivery/birth]
• Proportion of participants with a preterm birth (<37 weeks gestation) [Time frame: At pregnancy outcome/delivery/birth]
• Proportion of participants with an infant congenital anomaly consistent with the definition of defect provided by Metropolitan Atlanta Congenital Defects Program (MACDP) [Time frame: At pregnancy outcome/delivery/birth]

Eligibility criteria

Inclusion criteria

• Is of legal age or circumstance to provide independent informed consent as determined by site standard operating procedures (SOPs) and consistent with Institutional Review Board (IRB) policies and procedures and is willing and able to provide written informed consent for her own and, if applicable (Arm 2), her infant's study participation
• At screening, has a viable singleton intrauterine pregnancy of any gestational age confirmed by fetal ultrasound, as determined by the site investigator based on medical records, with trimester documented based on the best available obstetric estimate
• At screening, is receiving or expected to receive one of the following drugs under study as prescribed by a clinical care provider and documented in medical records:

• Ceftriaxone: IV or IM administration for an indication other than syphilis
• Benzathine penicillin G: IM administration for treatment of syphilis
• At entry, expects to remain in the geographic area of the study site during pregnancy and at least 30 days postpartum

Exclusion criteria

• Previously enrolled in this study
• Requires desensitization to ceftriaxone or benzathine penicillin G as determined by the site investigator based on pregnant participant report and available medical records
• Has any of the following as determined by the site investigator based on pregnant participant report and available medical records:

• Current indication for hemodialysis
• Current indication for intensive care unit hospitalization
• Creatinine (Cr) ≥ 3.5 x upper limit of normal (ULN) at any time during the current pregnancy and/or chronic kidney disease Stage 5
• Receipt of any of the following prohibited medications within seven days prior to entry as determined by the site investigator based on pregnant participant report and available medical records:

• Probenecid
• Penicillin
• Arm 1A: any penicillin
• Arm 1B: any penicillin
• Arm 2: penicillin other than benzathine penicillin G

• Benzapril
• Chlorpropamide
• Diflunisal
• Irbesartan
• Ketoprofen
• Ketorolac tromethamine
• Meclofenamic acid
• Mefenamic acid
• Oxaprozin
• Parecoxib
• Penciclovir
• Pioglitazone
• Telmisartan
• Valsartan
• Receipt of any investigational agent within seven days prior to entry as determined by the site investigator based on pregnant participant report and available medical records
• Has any documented or suspected clinically significant condition that, in the opinion of the site investigator, would make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving study objectives

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

United States · 8 centers

• Site 5048, USC - Maternal Child Adolescent/Adult Center — Los Angeles
• Site 5112, David Geffen School of Medicine at UCLA NICHD CRS — Los Angeles
• Site 5083, Rush Univ. Cook County Hosp. Chicago NICHD CRS — Chicago
• Site 4001, Lurie Children's Hospital of Chicago (LCH) CRS — Chicago
• Site 5040, SUNY Stony Brook NICHD CRS — Stony Brook
• Site 5114, Bronx-Lebanon Hospital Center NICHD CRS — The Bronx
• Site 5013, Jacobi Med. Ctr. Bronx NICHD CRS — The Bronx
• Site 5128, Baylor College of Medicine/Texas Children's Hospital NICHD CRS — Houston

Puerto Rico · 1 center

• Site 5129, IMPAACT/Gamma Project/UPR Pediatric HIV/AIDS Research CRS — San Juan

Identifiers

NCT: NCT07207876 · IMPAACT 2044 · UM1AI068632 · UM1AI068616 · UM1AI106716 · HHSN275201800001I

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗