{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T17:58:43Z","timestamp":1781719123057,"version":"3.54.5"},"reference-count":27,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016374","name":"Cures Within Reach","doi-asserted-by":"publisher","award":["2025CWR-LMIC-1051321858"],"award-info":[{"award-number":["2025CWR-LMIC-1051321858"]}],"id":[{"id":"10.13039\/100016374","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000061","name":"Fogarty International Center","doi-asserted-by":"publisher","award":["K43TW011930"],"award-info":[{"award-number":["K43TW011930"]}],"id":[{"id":"10.13039\/100000061","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Despite significant advancements in obstetric care, the incidence of preeclampsia remains a substantial public health challenge, and effective strategies to prevent the disease progression remain limited, particularly in low-resource settings. N-acetylcysteine (NAC), an antioxidant and glutathione precursor, has demonstrated anti-inflammatory and vasodilatory effects, making it a promising candidate for repurposing. However, robust evidence from well-powered randomized controlled trials is lacking.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study will evaluate the impact of NAC on the time-to-disease progression in pregnant women with early-onset preeclampsia in Lagos, Nigeria.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This is the study protocol for a proof-of-concept, double-blind, randomized, controlled trial to be conducted between April 2026 to July 2028 at the maternity units of the two teaching hospitals in Lagos, Nigeria. At baseline, n\u2009=\u2009153 sexually active women aged 18 years or older diagnosed with early-onset preeclampsia at 24\u201334 weeks\u2019 gestation will be randomised to receive either daily oral tablet containing 600 mg of NAC or a placebo tablet that is matched for appearance and the dosing regimen in addition to standard antenatal care from diagnosis (randomisation) until either 34 weeks\u2019 gestation or delivery, whichever comes first. The primary endpoint is the time-to-progression (in days) of early-onset preeclampsia to severe disease. The data analysis will be conducted on an intention-to-treat basis. Kaplan-Meier estimates with a Log-rank test will be used to calculate and compare the time-to-disease progression for the treatment groups, while Cox proportional hazard models with a backwards conditional method will be used to compare the primary endpoint between the treatment arms while adjusting for other covariates for precision using hazard ratios (HRs) and 95% confidence intervals (95%CIs). Subgroup analyses will also be performed to assess the differential effects of significant covariates on the impact of NAC on disease progression. Statistical significance will be reported as\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.05.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>This study will evaluate the efficacy of daily oral NAC compared to placebo in treating pregnant women with early-onset preeclampsia. If proven effective, NAC could offer a safe, affordable, and scalable intervention to reduce the burden of preeclampsia, particularly in resource-constrained settings.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0347695","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T17:27:54Z","timestamp":1781717274000},"page":"e0347695","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["A randomized controlled trial of N-acetylcysteine in the treatment of early-onset preeclampsia: Study Protocol"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0957-7389","authenticated-orcid":true,"given":"Kehinde S.","family":"Okunade","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adebola 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