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Standard-of-care (SOC) for BV are antibiotics; however, cure rates are low. Probiotics for vaginal health may be useful in improving cure and recurrence although the regulatory framework governing probiotics and the conduct of randomized clinical trials to evaluate these has not been established in South Africa. We performed an exploratory single-blind trial evaluating a commercial oral-vaginal-combination probiotic as adjunct to SOC for BV treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Women with symptomatic vaginal discharge were screened for BV and common sexually transmitted infections (STIs). BV+ (Nugent 7\u201310) but STI- women were randomized to vaginal metronidazole alone (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200912) or to metronidazole followed by a commercial oral\/vaginal probiotic (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200918). The primary qualitative outcome was to test the regulatory landscape for conducting randomized probiotic trials in South Africa; and acceptability of vaginal application by women. BV cure at 1 month (Nugent\u22643) was the primary quantitative endpoint. Secondary quantitative endpoints were BV recurrence, symptoms, vaginal microbiota and genital cytokine changes over 5 months post-treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The\u00a0 South African Health Products Regulatory Authority (SAHPRA) reviewed and approved this trial. As probiotics continue to be regulated as health supplements in South Africa, SAHPRA required a notification application for this trial. Acceptability and adherence to the oral and vaginal application of the probiotic were high, although women reported a preference for oral capsules. 44.8% of women cleared BV one-month post-treatment, and no significant differences in BV cure (RR\u2009=\u20090.52, 95% CI\u2009=\u20090.24\u20131.16), recurrence, vaginal pH, symptoms, microbiota or vaginal IL-1\u03b1 concentrations were found between SOC and intervention groups in this pilot study with an over-the-counter product.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Navigation of the SAHPRA registration process for evaluating a commercial probiotic in a randomised trial laid the foundation for planned larger trials of improved probiotic products for vaginal health in South Africa. Although adherence to the vaginally delivered probiotic was high, women preferred oral application and we recommend that improvements in the content and method of application for future probiotics for vaginal health should be considered.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>\n                      This trial was registered on 17 October 2017 with the South African National Clinical Trial Register (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.sanctr.gov.za\/\">http:\/\/www.sanctr.gov.za\/<\/jats:ext-link>\n                      ; BV-trial1;\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.sanctr.gov.za\/SAClinicalbrnbspTrials\/tabid\/169\/Default.aspx\">DOH-27-1117-5579<\/jats:ext-link>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12879-020-05210-4","type":"journal-article","created":{"date-parts":[[2020,7,10]],"date-time":"2020-07-10T03:03:42Z","timestamp":1594350222000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Testing the regulatory framework in South Africa \u2013 a single-blind randomized pilot trial of commercial probiotic supplementation to standard therapy in women with bacterial vaginosis"],"prefix":"10.1186","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3658-8638","authenticated-orcid":false,"given":"Anna-Ursula","family":"Happel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravesh","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nireshni","family":"Mitchev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koleka","family":"Mlisana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather B.","family":"Jaspan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaun L.","family":"Barnabas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo-Ann S.","family":"Passmore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,7,10]]},"reference":[{"issue":"6","key":"5210_CR1","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1016\/j.ajog.2013.05.006","volume":"209","author":"C Kenyon","year":"2013","unstructured":"Kenyon C, Colebunders R, Crucitti T. 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The trial was registered with the South African National Clinical Trial Register of the Department of Health (DOH-27-1117-5579; PI: S. Barnabas) and conducted in full compliance with South African Good Clinical Practice (SA-GCP) and International Conference on Harmonisation (ICH)-GCP, supported by the UCT Clinical Research Centre (CRC). Before undergoing any trial-related procedures, all women provided written informed consent.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"None of the authors reported any conflict of interest. We confirm that none of the manufacturers were involved in the design or testing of this product and did not contribute financially in any way towards the conduct of this study. In addition, we confirm that none of the authors involved in this study are associated in any way financially or otherwise with the manufacturers.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"491"}}