Pregnancy
Conditions
Keywords
Cefriaxone, Syphilis, Pregnancy, Benzathine Penicillin G
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.
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
DRUGCeftriaxon
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
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
Sponsors
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
National Institute of Allergy and Infectious Diseases (NIAID)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institute of Mental Health (NIMH)
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Geometric mean area under the curve (AUC) during the dosing interval (AUC0-tau) in the first trimester trimester | First on-study dose through 24 hours | Arm 1A |
| Geometric mean terminal elimination half-life (t1/2) in the first trimester | First on-study dose through 24 hours | Arm 1A |
| Geometric mean trough concentration (Ctrough) in the first trimester | First on-study dose through 24 hours | Arm 1A |
| Geometric mean AUC0-tau in the second trimester | First on-study dose through 24 hours | Arm 1A |
| Geometric mean t1/2 in the second trimester | First on-study dose through 24 hours | Arm 1A |
| Geometric mean Ctrough in the second trimester | First on-study dose through 24 hours | Arm 1A |
| Geometric mean AUC0-tau in the third trimester | First on-study dose through 24 hours | Arm 1A |
| Geometric mean t1/2 in the third trimester | First on-study dose through 24 hours | Arm 1A |
| Geometric mean Ctrough in the third trimester | First on-study dose through 24 hours | Arm 1A |
| Median maximum plasma concentration during the dose interval (Cmax) in the first trimester | First on-study dose through up to 24 hours | Arm 1B |
| Median time to Cmax (Tmax) in the first trimester | First on-study dose through up to 24 hours | Arm 1B |
| Median Cmax in the second trimester | First on-study dose through up to 24 hours | Arm 1B |
| Median Tmax in the second trimester | First on-study dose through up to 24 hours | Arm 1B |
| Median Cmax in the third trimester | First on-study dose through up to 24 hours | Arm 1B |
| Median Tmax in the third trimester | First on-study dose through up to 24 hours | Arm 1B |
| Geometric mean AUC at 7 days (AUC 0-7d) in the first trimester | First on-study dose through 7 days | Arm 2 |
| Geometric mean AUC at 14 days (AUC0-14d) in the first trimester | First on-study dose through 14 days | Arm 2 |
| Geometric mean plasma concentration at 2 hours (C2h) in the first trimester | 2 hours post-first on-study dose | Arm 2 |
| Geometric mean plasma concentration at 24 hours (C24h) in the first trimester | 24 hours post-first on-study dose | Arm 2 |
| Geometric mean plasma concentration at 4 days (C4d) in the first trimester | 4 days post-first on-study dose | Arm 2 |
| Geometric mean plasma concentration at 7 days (C7d) in the first trimester | 7 days post-first on-study dose | Arm 2 |
| Geometric mean plasma concentration at 14 days (C14d) in the first trimester | 14 days post-first on-study dose | Arm 2 |
| Geometric mean AUC0-7d in the second trimester | First on-study dose through 7 days | Arm 2 |
| Geometric mean AUC0-14d in the second trimester | First on-study dose through 14 days | Arm 2 |
| Geometric mean C2h in the second trimester | 2 hours post-first on-study dose | Arm 2 (as defined above) |
| Geometric mean C24h in the second trimester | 24 hours post-first on-study dose | Arm 2 (as defined above) |
| Geometric mean C4d in the second trimester | 4 days post-first on-study dose | Arm 2 (as defined above) |
| Geometric mean C7d in the second trimester | 7 days post-first on-study dose | Arm 2 (as defined above) |
| Geometric mean C14d in the second trimester | 14 days post-first on-study dose | Arm 2 (as defined above) |
| Geometric mean AUC0-7d in the third trimester | First on-study dose through 7 days | Arm 2 |
| Geometric mean AUC0-14d in the third trimester | First on-study dose through 14 days | Arm 2 |
| Geometric mean C2h in the third trimester | 2 hours post-first on-study dose | Arm 2 (as defined above) |
| Geometric mean C24h in the third trimester | 24 hours post-first on-study dose | Arm 2 (as defined above) |
| Geometric mean C4d in the third trimester | 4 days post-first on-study dose | Arm 2 (as defined above) |
| Geometric mean C7d in the third trimester | 7 days post-first on-study dose | Arm 2 (as defined above) |
| Geometric mean C14d in the third trimester | 14 days post-first on-study dose | Arm 2 (as defined above) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants with a maternal serious adverse event (SAE) | First on-study dose through 7 days | Arm 1A and Arm 1B |
| Proportion of participants with a maternal SAE assessed as related to drug under study | First on-study dose through 7 days | Arm 1A and Arm 1B |
| Proportion of participants with a maternal SAE | First on-study dose through up to 28 days | Arm 2 |
| Proportion of participants with a spontaneous abortion or miscarriage (<20 weeks gestation) | At pregnancy outcome/delivery/birth | Arm 1A, Arm1B, and Arm 2 |
| Proportion of participants with a stillbirth (≥20 weeks gestation) | At pregnancy outcome/delivery/birth | Arm 1A, Arm1B, and Arm 2 |
| Proportion of participants with an infant small for gestational age (SGA; weight <10th percentile for gestational age, adjusted for sex) | At pregnancy outcome/delivery/birth | Arm 1A, Arm1B, and Arm 2 |
| Proportion of participants with a preterm birth (<37 weeks gestation) | At pregnancy outcome/delivery/birth | Arm 1A, Arm1B, and Arm 2 |
| Proportion of participants with an infant congenital anomaly consistent with the definition of defect provided by Metropolitan Atlanta Congenital Defects Program (MACDP) | At pregnancy outcome/delivery/birth | Arm 1A, Arm1B, and Arm 2 |
Countries
Puerto Rico, United States
Contacts
CONTACTLisa Levy
STUDY_CHAIRJason Zucker
Columbia Physicians & Surgeons (P&S) CRS
Outcome results
None listed