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, which will be determined through the undertaking of a series of pharmacokinetic studies (Study 1-3). Study 3, a transplacental cefixime transfer study, aims to investigate the mechanisms of maternal/neonate transfer of cefixime, and the transfer dynamics of cefixime into breast milk. As participants from Study 1 and Study 2 will also participate in Study 3, the data generated in Study 3 will be used alongside previous generated pharmacokinetic data (both individual and population) to determine whether current dosing strategies provide sufficient cefixime exposure to the foetus to effectively treat syphilis (Treponema bacterium), preventing congenital syphilis.
Interventions
At the time of active labour, once the cervix is confirmed to be dilated >6cm, participants will be given a single 400 mg oral (capsule) dose of Cefixime with water as directly observed treatment
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
Yes
Inclusion criteria
Pregnant women who have previously participated in Study 1 and Study 2 of the broader Cefixime dose ranging pharmacokinetic studies are prioritised for recruitment into the transplacental PK study (Study 3 of broad program). Key inclusion criteria includes: ii) >/=18 years of age at time of enrolment ii) Provides informed consent (including verbal consent from husband/father, as culturally appropriate, should the woman feel appropriate) iii) Agreement to deliver their baby at the Alexishafen Health Centre Labour ward iv) No signs of maternal malaria or other significant concomitant disease v) No allergies to penicillin or cephalosporins – confirmed through verbal reporting and review of woman’s health book for evidence of medical documentation.
Exclusion criteria
i) <18 years of age at time of enrolment ii) Does not provide informed consent (including verbal consent from husband/father, as culturally appropriate, should the woman feel appropriate) iii) Does not agree to deliver their baby at the Alexishafen Health Centre Labour ward iv) Signs of maternal malaria or other significant concomitant disease at time of delivery v) Reported allergies to penicillin or cephalosporins
Outcome results
None listed