Study of Ceftriaxone and Benzathine Penicillin G During Pregnancy

NCT07207876 | Recruiting DMC FDA Drug

• 5 other identifiers: IMPAACT 2044UM1AI068632UM1AI068616UM1AI106716HHSN275201800001I
• Study Type: observational
• Target: 110
• Locations: 2 countries
• Sites: 9

Brief Summary

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.

Conditions

Pregnancy

Keywords

Cefriaxone; Syphilis; Pregnancy; Benzathine Penicillin G

Outcome Measures

Primary Outcomes (36)

• Geometric mean area under the curve (AUC) during the dosing interval (AUC0-tau) in the first trimester trimester

  Arm 1A

  First on-study dose through 24 hours

• Geometric mean terminal elimination half-life (t1/2) in the first trimester

  Arm 1A

  First on-study dose through 24 hours

• Geometric mean trough concentration (Ctrough) in the first trimester

  Arm 1A

  First on-study dose through 24 hours

• Geometric mean AUC0-tau in the second trimester

  Arm 1A

  First on-study dose through 24 hours

• Geometric mean t1/2 in the second trimester

  Arm 1A

  First on-study dose through 24 hours

• Geometric mean Ctrough in the second trimester

  Arm 1A

  First on-study dose through 24 hours

• Geometric mean AUC0-tau in the third trimester

  Arm 1A

  First on-study dose through 24 hours

• Geometric mean t1/2 in the third trimester

  Arm 1A

  First on-study dose through 24 hours

• Geometric mean Ctrough in the third trimester

  Arm 1A

  First on-study dose through 24 hours

• Median maximum plasma concentration during the dose interval (Cmax) in the first trimester

  Arm 1B

  First on-study dose through up to 24 hours

• Median time to Cmax (Tmax) in the first trimester

  Arm 1B

  First on-study dose through up to 24 hours

• Median Cmax in the second trimester

  Arm 1B

  First on-study dose through up to 24 hours

• Median Tmax in the second trimester

  Arm 1B

  First on-study dose through up to 24 hours

• Median Cmax in the third trimester

  Arm 1B

  First on-study dose through up to 24 hours

• Median Tmax in the third trimester

  Arm 1B

  First on-study dose through up to 24 hours

• Geometric mean AUC at 7 days (AUC 0-7d) in the first trimester

  Arm 2

  First on-study dose through 7 days

• Geometric mean AUC at 14 days (AUC0-14d) in the first trimester

  Arm 2

  First on-study dose through 14 days

• Geometric mean plasma concentration at 2 hours (C2h) in the first trimester

  Arm 2

  2 hours post-first on-study dose

• Geometric mean plasma concentration at 24 hours (C24h) in the first trimester

  Arm 2

  24 hours post-first on-study dose

• Geometric mean plasma concentration at 4 days (C4d) in the first trimester

  Arm 2

  4 days post-first on-study dose

• Geometric mean plasma concentration at 7 days (C7d) in the first trimester

  Arm 2

  7 days post-first on-study dose

• Geometric mean plasma concentration at 14 days (C14d) in the first trimester

  Arm 2

  14 days post-first on-study dose

• Geometric mean AUC0-7d in the second trimester

  Arm 2

  First on-study dose through 7 days

• Geometric mean AUC0-14d in the second trimester

  Arm 2

  First on-study dose through 14 days

• Geometric mean C2h in the second trimester

  Arm 2 (as defined above)

  2 hours post-first on-study dose

• Geometric mean C24h in the second trimester

  Arm 2 (as defined above)

  24 hours post-first on-study dose

• Geometric mean C4d in the second trimester

  Arm 2 (as defined above)

  4 days post-first on-study dose

• Geometric mean C7d in the second trimester

  Arm 2 (as defined above)

  7 days post-first on-study dose

• Geometric mean C14d in the second trimester

  Arm 2 (as defined above)

  14 days post-first on-study dose

• Geometric mean AUC0-7d in the third trimester

  Arm 2

  First on-study dose through 7 days

• Geometric mean AUC0-14d in the third trimester

  Arm 2

  First on-study dose through 14 days

• Geometric mean C2h in the third trimester

  Arm 2 (as defined above)

  2 hours post-first on-study dose

• Geometric mean C24h in the third trimester

  Arm 2 (as defined above)

  24 hours post-first on-study dose

• Geometric mean C4d in the third trimester

  Arm 2 (as defined above)

  4 days post-first on-study dose

• Geometric mean C7d in the third trimester

  Arm 2 (as defined above)

  7 days post-first on-study dose

• Geometric mean C14d in the third trimester

  Arm 2 (as defined above)

  14 days post-first on-study dose

Secondary Outcomes (9)

• Proportion of participants with a maternal serious adverse event (SAE)

  First on-study dose through 7 days

• Proportion of participants with a maternal SAE assessed as related to drug under study

  First on-study dose through 7 days

• Proportion of participants with a maternal SAE

  First on-study dose through up to 28 days

• Proportion of participants with a maternal SAE assessed as related to drug under study

  First on-study dose through up to 28 days

• Proportion of participants with a spontaneous abortion or miscarriage (<20 weeks gestation)

  At pregnancy outcome/delivery/birth

Study Arms (3)

Active comparator: Arm 1A: IV ceftriaxone

Intravenous ceftriaxone

Drug: Ceftriaxon

Active Comparator: Arm 1B: IM ceftriaxone

Intramuscular ceftriaxone

Drug: Ceftriaxon

Active Comparator: Arm 2: IM benzathine penicillin G

Intramuscular benzathine penicillin G

Drug: Benzathine penicillin G

Interventions

Ceftriaxon DRUG

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

Active Comparator: Arm 1B: IM ceftriaxone; Active comparator: Arm 1A: IV ceftriaxone

Benzathine penicillin G DRUG

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

Active Comparator: Arm 2: IM benzathine penicillin G

Eligibility Criteria

• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Women receiving or expecting to receive ceftriaxone for indications other than syphilis or benzathine penicillin G for treatment of syphilis during pregnancy in the United States (US). The infants of pregnant participants receiving benzathine penicillin G will also be enrolled.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• International Maternal Pediatric Adolescent AIDS Clinical Trials Group: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• National Institute of Mental Health (NIMH): collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (9)

Site 5048, USC - Maternal Child Adolescent/Adult Center

Los Angeles, California, 90033, United States

NOT YET RECRUITING

Site 5112, David Geffen School of Medicine at UCLA NICHD CRS

Los Angeles, California, 90095, United States

RECRUITING

Site 5083, Rush Univ. Cook County Hosp. Chicago NICHD CRS

Chicago, Illinois, 60612, United States

NOT YET RECRUITING

Site 4001, Lurie Children's Hospital of Chicago (LCH) CRS

Chicago, Illinois, 60614, United States

RECRUITING

Site 5040, SUNY Stony Brook NICHD CRS

Stony Brook, New York, 11794, United States

RECRUITING

Site 5114, Bronx-Lebanon Hospital Center NICHD CRS

The Bronx, New York, 10457, United States

RECRUITING

Site 5013, Jacobi Med. Ctr. Bronx NICHD CRS

The Bronx, New York, 10461, United States

NOT YET RECRUITING

Site 5128, Baylor College of Medicine/Texas Children's Hospital NICHD CRS

Houston, Texas, 77030, United States

NOT YET RECRUITING

Site 5129, IMPAACT/Gamma Project/UPR Pediatric HIV/AIDS Research CRS

San Juan, 00935, Puerto Rico

NOT YET RECRUITING

MeSH Terms

Conditions

Syphilis

Interventions

Ceftriaxone; Penicillin G

Condition Hierarchy (Ancestors)

Treponemal Infections; Spirochaetales Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Sexually Transmitted Diseases, Bacterial; Sexually Transmitted Diseases; Communicable Diseases; Genital Diseases; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Cefotaxime; Cephacetrile; Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Penicillins

Study Officials

• Jason Zucker

  Columbia Physicians & Surgeons (P&S) CRS

  STUDY CHAIR

Central Study Contacts

Lisa Levy

CONTACT

2028848480; impaact.ctgov@fstrf.org

Lisa Levy

CONTACT

2028848480; llevy@fhi360.org

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 19, 2025
• First Posted: October 6, 2025
• Study Start: February 16, 2026
• Primary Completion (Estimated): August 29, 2026
• Study Completion (Estimated): May 17, 2027
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 3 months following publication and available throughout period of funding of the International Maternal Pediatric Adolescent AIDS Clinical Trial (IMPAACT) Network by NIH.
• Access Criteria: * With whom? Researchers who provide a methodologically sound proposal for use of the data that is approved by the IMPAACT Network. * For what types of analyses? To achieve aims in the proposal approved by the IMPAACT Network. * By what mechanism will data be made available? Researchers may submit a request for access to data using the IMPAACT "Data Request" form at: https://www.impaactnetwork.org/studies/submit-research-proposal. Researchers of approved proposals will need to sign an IMPAACT Data Use Agreement before receiving the data.

Locations

PR (1); US (8)