None listed
Conditions
Brief summary
There is an urgent need for new treatments for syphilis in pregnancy to prevent congenital syphilis. Benzathine penicillin G (BPG; 2.4 MU) is currently the only recommended treatment for pregnant patients to treat maternal syphilis and prevent congenital syphilis, however global challenges with BPG supply and distribution have led to recurrent global shortages which have compounded the local challenges of poor adherence and low acceptability of intramuscular (IM) BPG. Cefixime, an oral broad-spectrum cephalosporin, may be an effective alternative to IM BPG for treatment of syphilis and prevention of congenital syphilis. There is little data on the pharmacology of cefixime in pregnancy, and no comprehensive pharmacokinetic studies have been performed in pregnant women, justifying detailed pharmacokinetic safety and dose finding studies prior to further deployment of this alternative treatment strategy. The overall aim of this research is to inform the suitability and optimal dosing strategy for cefixime as an alternative treatment to BPG for antenatal syphilis. Study 2, a safety, tolerability and population pharmacokinetic study of prolonged, optimised cefixime (daily dose to be adapted from results from Study 1) in pregnant Papua New Guinean women, aims to evaluate the safety, tolerability and pharmacokinetic disposition of cefixime after multiple doses are administered. Data generated within this study will inform whether a 14-day regimen of cefixime is safe and well tolerated for use in pregnancy, whilst population pharmacokinetics will inform optimised treatment doses and duration. Furthermore, simulations of foetal transplacental exposure generated in Study 1 will be optimised based on multiple dose profiles determined in this study. Furthermore, data generated in Study 2 will inform interpretation and modelling of pharmacokinetic data generated in Study 3
Interventions
Healthy pregnant women (14-32 weeks gestation): Oral cefixime 400 mg (capsule) twice daily (12-h apart) for 14 days. Morning doses to be administered as directly observed treatment by study staff, with evening doses dispensed daily with dosing instructions (evening treatment confirmed by return of empty pill container, and verbal confirmation).
Sponsors
World Health Organization
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Prevention
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
All pregnant women will be eligible to participate in the trial, providing they have the following inclusion criteria: a) In the second or third trimester of pregnancy (14-32 weeks gestation). b) >/=18 years of age at time of enrolment c) Provides informed consent (including verbal consent from husband/father, as culturally appropriate, should the woman feel appropriate) d) Tested negative for syphilis and HIV e) No signs of malaria or other significant concomitant disease f) Haemoglobin concentration >10 g/dL g) No known allergies to penicillin or cephalosporins – confirmed through verbal reporting and review of woman’s health book for evidence of medical documentation. h) No history of complicated pregnancies i) Agreement to attend all study visits.
Exclusion criteria
Pregnant women will not be eligible to participate in the trial, if they have the following exclusion criteria: a) Are not in the second or third trimester of pregnancy (14-32 weeks gestation). b) < 18 years of age at time of enrolment c) Does not provide informed consent (including verbal consent from husband/father, as culturally appropriate, should the woman feel appropriate) d) Tested positive for syphilis and HIV (as documented in participant health book; testing conducted as part of routine antenatal care prior to study screening procedures) e) Has signs of malaria or other significant concomitant disease f) Haemoglobin concentration <10 g/dL g) Is allergic to penicillin or cephalosporins – confirmed through verbal reporting and review of woman’s health book for evidence of medical documentation. h) History of complicated pregnancies i) Does not agree to attend all study visits.
Outcome results
None listed