Background <p>Preterm premature rupture of membranes is a major cause of preterm birth and is associated with substantial maternal and neonatal morbidity. Current management is largely uniform and includes routine administration of antibiotics and antenatal corticosteroids, although a considerable proportion of women do not have infection or inflammation at the time of membrane rupture. This approach may lead to unnecessary exposure to medication and suboptimal timing of treatment. Measurement of interleukin-6 in amniotic fluid is a promising marker of intra-amniotic inflammation and may allow a more individualized management strategy. The aim of this study is to evaluate whether tailored antibiotic and corticosteroid therapy based on interleukin-6 levels in amniotic fluid can prolong pregnancy compared with standard care.</p> Methods <p>This is a prospective, randomised controlled trial conducted at two tertiary perinatal centres. Pregnant women aged 18 years or older with singleton pregnancies complicated by confirmed preterm premature rupture of membranes between 22 + 0 and 33 + 6 weeks of gestation will be eligible. After providing signed informed consent, participants will be randomised in a 1:1 ratio to tailored management or standard care. In the tailored arm, transabdominal amniocentesis will be performed within 24&#xa0;h of admission, and subsequent antibiotic and corticosteroid therapy will be guided by the interleukin-6 concentration in amniotic fluid. In the standard care arm, antibiotics and antenatal corticosteroids will be administered at admission according to current guidelines. The primary outcome is pregnancy latency longer than 7 days from membrane rupture to delivery. Secondary outcomes include overall latency to birth, maternal infectious and non-infectious morbidity, and short-term neonatal outcomes. A total of 138 women will be randomised to account for the expected drop-out and non-feasible amniocentesis.</p> Discussion <p>This trial addresses an important clinical question by testing a personalised approach to the management of preterm premature rupture of membranes. If effective, tailored treatment based on interleukin-6 measurement may prolong pregnancy, reduce unnecessary exposure to antibiotics and corticosteroids, and improve maternal and neonatal outcomes. The results may support a change toward more individualised care in this high-risk obstetric population.</p> Trial registration <p>EU Clinical Trials Register: 2024-520237-77-00. Registered on 30th March 2025.</p>