Ceftriaxone and benzathine penicillin G use during pregnancy

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

This project tests how ceftriaxone or benzathine penicillin G are processed by the body and how safe they are for pregnant women and some newborns.

Quick facts

• Study type: Observational
• Enrollment: 110 (estimated)
• Sex: Female
• Sponsor: International Maternal Pediatric Adolescent AIDS Clinical Trials Group (network)
• Locations: 9 sites (Los Angeles, California and 8 other locations)
• Trial ID: NCT07207876 on ClinicalTrials.gov

What this trial studies

IMPAACT 2044 is a Phase IV, multi-site, open-label, non-randomized, opportunistic study that will measure pharmacokinetics and safety of ceftriaxone and benzathine penicillin G during pregnancy. Up to 78 pregnant women who are already being treated with IV or IM ceftriaxone (for non-syphilis indications) or IM benzathine penicillin G (for syphilis) will be enrolled, and about 22 infants of participants receiving benzathine penicillin G will also be followed. Participants are assigned to Arm 1 (ceftriaxone, subdivided into IV and IM groups) or Arm 2 (IM benzathine penicillin G) based on the antibiotic prescribed by their clinical provider, with no randomization. The study collects blood samples and safety data around routine clinical care visits to characterize drug levels and monitor mother and infant safety.

Who should consider this trial

Good fit: Pregnant women with a viable singleton pregnancy who are already prescribed IV or IM ceftriaxone for non-syphilis indications or IM benzathine penicillin G for syphilis, who can provide informed consent and remain near a study site, are ideal candidates.

Not a fit: Women not taking ceftriaxone or benzathine penicillin G, those with multiple gestation, or those unable to remain in the geographic area for study visits are unlikely to receive benefit from participation.

Why it matters

Potential benefit: If successful, the results could help clinicians choose safer and better-informed dosing for ceftriaxone and benzathine penicillin G in pregnancy to improve outcomes for mothers and babies.

How similar studies have performed: Benzathine penicillin G is long-established for treating syphilis in pregnancy but detailed pregnancy pharmacokinetic data are limited, and ceftriaxone has some pregnancy PK data though opportunistic PK designs like this are less common.

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

Where this trial is running

Los Angeles, California and 8 other locations

• Site 5048, USC - Maternal Child Adolescent/Adult Center — Los Angeles, California, United States (NOT_YET_RECRUITING)
• Site 5112, David Geffen School of Medicine at UCLA NICHD CRS — Los Angeles, California, United States (RECRUITING)
• Site 5083, Rush Univ. Cook County Hosp. Chicago NICHD CRS — Chicago, Illinois, United States (NOT_YET_RECRUITING)
• Site 4001, Lurie Children's Hospital of Chicago (LCH) CRS — Chicago, Illinois, United States (RECRUITING)
• Site 5040, SUNY Stony Brook NICHD CRS — Stony Brook, New York, United States (RECRUITING)
• Site 5114, Bronx-Lebanon Hospital Center NICHD CRS — The Bronx, New York, United States (RECRUITING)
• Site 5013, Jacobi Med. Ctr. Bronx NICHD CRS — The Bronx, New York, United States (NOT_YET_RECRUITING)
• Site 5128, Baylor College of Medicine/Texas Children's Hospital NICHD CRS — Houston, Texas, United States (NOT_YET_RECRUITING)
• Site 5129, IMPAACT/Gamma Project/UPR Pediatric HIV/AIDS Research CRS — San Juan, Puerto Rico (NOT_YET_RECRUITING)

Study contacts

• Study coordinator: Lisa Levy

Conditions: Pregnancy, Cefriaxone, Syphilis, Benzathine Penicillin G