TAILORED Therapeutic Regime in Patients With Preterm Premature Rupture Of Membranes to Prolong Pregnancy, Improve Maternal and Neonatal Outcomes, and Reduce Antibiotic Burden

Официальное название

Prospective Randomized Controlled Trial to Evaluate if Tailored Antibiotic and Steroid Therapy Based on the Interleukin-6 (IL-6) Value in Amniotic Fluid Obtained by Amniocentesis in Patients With Premature Rupture of Membranes is Associated With Pregnancy Prolongation Compared to Standard Management.

Обзор

The goal of this clinical trial is to learn whether tailoring antibiotic and steroid treatment based on a lab result (interleukin-6, or IL-6) from amniotic fluid can help safely prolong pregnancy in people with preterm premature rupture of membranes (pPROM). This condition means the water breaks too early, before 37 weeks of pregnancy, which increases the risk of infection and early birth. The main questions the study aims to answer are: 1. Can using IL-6 levels to guide treatment help the pregnancy last more than 7 days after pPROM? 2. Can this approach improve health outcomes for both the parent and the baby? Researchers will compare two groups: 1. A tailored treatment group, where IL-6 levels from amniotic fluid help decide when to give steroids and antibiotics. 2. A standard care group, where everyone receives the same treatment right after diagnosis. Participants will: * Be screened to confirm pPROM and eligibility. * Be randomly assigned to one of the two groups. * Receive regular check-ups and monitoring in the hospital until delivery. * In the tailored group, have weekly amniocentesis (a safe procedure to collect amniotic fluid) if needed. The study includes follow-up for 6 months after birth to track both the baby's and parent's health. This research may help doctors better time treatments, reduce unnecessary use of medications, and improve outcomes for families facing pPROM.

Вмешательства

• Процедура Tailored antibiotic and steroid therapy based on the IL-6 value in amniotic fluid obtained by amniocentesis in patients with premature rupture of membranes
  In Arm A, Amniocentesis will be performed once a week until delivery, with a maximum of seven procedures per patient. If the pregnancy continues beyond this period, follow-up will proceed without further amniocentesis. * If IL-6 ≥ 2600: * steroids and initial broad spectrum ABX will be administered, * rotation of ABX according to cultures and PCR. * If steroids already administered, a second course can be administered prior to 34+0 if at least 7 days have passed after the previous course.
• Препарат Antenatal steroids administration
  1. Clinical and/or laboratory signs of chorioamnionitis will result in an intervention consisting of the course of antenatal steroids (if not already administered, or as a single course prior 34+0 if at least 7 days have passed after the previous course), initial broad spectrum antibiotics, or delivery, depending on the week of pregnancy and clinical status. 2. Uterine activity with progression of vaginal finding will result in course of antenatal steroids (if not already administered, or as a s
• Препарат Neuroprotection
  In patients with imminent preterm birth prior 32+0 week of pregnancy, foetal neuroprotection will be administered consisting of MgSO4 in an intravenous loading dose of 4 g (administered slowly over 20-30 min), followed by a 1 g per hour maintenance dose. This regimen should continue until birth but should be stopped after 24 h if undelivered.
• Препарат antibiotic prophylaxis
  Antibiotics - Group B Streptococcus (GBS) prophylaxis + macrolides, always at admission.
• Препарат Antibiotics administration
  1. GBS prophylaxis + macrolides: Penicillin G (benzylpenicillin) 5mil IU IV initially and then 2-3 IU (dose adjusted to body weight) IV every 4h twice, then every 6h + Clarithromycin 500mg po every 12h for 7-10 days or till delivery. 2. Initial broad spectrum ABX: Ampicillin/sulbactam 3g IV every 6 hours + Gentamicin 5 mg/kg IV (\<60 kg 240 mg, 61-80 kg 320 mg, \>80 kg 400 mg) every 24h for 5-7 days according to the clinical state. Comments: Alternative ABX in patients with allergy to PCN/AMP:

Первичные конечные точки

• The latency of pregnancy of more than 7 days from premature rupture of membranes to delivery [Срок оценки: From enrollment to the delivery (0-98 days).]

Вторичные конечные точки (4)

• Latency to birth [Срок оценки: Measured in days from pPROM to birth (0-98 days).]
• Incidence of chorioamnionitis and funisitis [Срок оценки: From the enrollment to the delivery (0-98 days).]
• Short-term adverse maternal outcomes [Срок оценки: From the enrollment to the 6 weeks postpartum. Time from enrollment to delivery is 0-14 weeks. Time frame ranges from 0-20 weeks.]
• Short-term neonatal outcomes [Срок оценки: From the birth to 6-months postpartum.]

Критерии участия

Критерии включения

• pPPROM Confirmed by Amnisure test1 and/or clinical signs of pPROM on examination (Clinical signs of pPROM: presence of visual pooling of amniotic fluid during sterile speculum examination)
• Weeks of pregnancy 22+03 - 33+64
• Singleton pregnancy
• Signed informed consent form (ICF)
• Completely uncomplicated pregnancy until the occurrence of pPROM

Критерии исключения

• active labour (uterine activity leading to cervical dilatation greater than 4 cm)
• Obstetrical reason for immediate delivery such as heavy vaginal bleeding, prolapsed cord, or foetal distress
• Multiple pregnancy
• Pregnancy with chromosomal or severe morphological abnormality
• Signs of chorioamnionitis at the admission (clinical and/or laboratory)
• Patients with severe immunological compromise (immunodeficient)
• Patients with an oncological disease/immunosuppression
• Patients with an active drug abuse
• Non-compliant patients
• Any contraindication according to the valid SmPC for the administered product

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Чехия · 3 центра

• University Hospital Brno — Brno
• General University Hospital in Prague — Prague
• Institute for Mother and Child Care in Prague - Podolí — Prague

Публикации

• Brun R, Girsberger J, Rothenbuhler M, Argyle C, Hutmacher J, Haslinger C, Leeners B. Wearable sensors for prediction of intraamniotic infection in women with preterm premature rupture of membranes: a prospective proof of principle study. Arch Gynecol Obstet. 2023 Nov;308(5):1447-1456. doi: 10.1007/s00404-022-06753-4. Epub 2022 Sep 13. PMID 36098832
• Visser GHA, Thommesen T, Di Renzo GC, Nassar AH, Spitalnik SL; FIGO Committee for Safe Motherhood, Newborn Health. FIGO/ICM guidelines for preventing Rhesus disease: A call to action. Int J Gynaecol Obstet. 2021 Feb;152(2):144-147. doi: 10.1002/ijgo.13459. Epub 2021 Jan 9. PMID 33128246
• Bond DM, Middleton P, Levett KM, van der Ham DP, Crowther CA, Buchanan SL, Morris J. Planned early birth versus expectant management for women with preterm prelabour rupture of membranes prior to 37 weeks' gestation for improving pregnancy outcome. Cochrane Database Syst Rev. 2017 Mar 3;3(3):CD004735. doi: 10.1002/14651858.CD004735.pub4. PMID 28257562
• Jung E, Romero R, Yeo L, Diaz-Primera R, Marin-Concha J, Para R, Lopez AM, Pacora P, Gomez-Lopez N, Yoon BH, Kim CJ, Berry SM, Hsu CD. The fetal inflammatory response syndrome: the origins of a concept, pathophysiology, diagnosis, and obstetrical implications. Semin Fetal Neonatal Med. 2020 Aug;25(4):101146. doi: 10.1016/j.siny.2020.101146. Epub 2020 Oct 23. PMID 33164775
• Romero R, Chaemsaithong P, Chaiyasit N, Docheva N, Dong Z, Kim CJ, Kim YM, Kim JS, Qureshi F, Jacques SM, Yoon BH, Chaiworapongsa T, Yeo L, Hassan SS, Erez O, Korzeniewski SJ. CXCL10 and IL-6: Markers of two different forms of intra-amniotic inflammation in preterm labor. Am J Reprod Immunol. 2017 Jul;78(1):e12685. doi: 10.1111/aji.12685. Epub 2017 May 19. PMID 28544362
• Middleton P, Shepherd E, Flenady V, McBain RD, Crowther CA. Planned early birth versus expectant management (waiting) for prelabour rupture of membranes at term (37 weeks or more). Cochrane Database Syst Rev. 2017 Jan 4;1(1):CD005302. doi: 10.1002/14651858.CD005302.pub3. PMID 28050900
• Romero R, Espinoza J, Goncalves LF, Kusanovic JP, Friel L, Hassan S. The role of inflammation and infection in preterm birth. Semin Reprod Med. 2007 Jan;25(1):21-39. doi: 10.1055/s-2006-956773. PMID 17205421
• Goldenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and causes of preterm birth. Lancet. 2008 Jan 5;371(9606):75-84. doi: 10.1016/S0140-6736(08)60074-4. PMID 18177778

Идентификаторы

NCT: NCT07107477 · TAILORED-PROM 2024-520237-77-0

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗