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RecruitingNCT07107477TAILORED-PROMUpdated Jun 18, 2026

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

A Phase 3 interventional study of Tailored antibiotic and steroid therapy based on the IL-6 value in amniotic fluid obtained by amniocentesis in patients with premature rupture of membranes and Antenatal steroids administration in Preterm Premature Rupture of Membranes (PPROM), sponsored by The Central and Eastern European Gynecologic Oncology Group. Recruiting at 3 sites in Czechia. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-06-18.

Sponsored by The Central and Eastern European Gynecologic Oncology Group · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
138
Allocation
Randomized
Ages
18 Years and older
Sex
Female
01

Study summary

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.

02

Conditions studied

  • Preterm Premature Rupture of Membranes (PPROM)
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
Female
Accepts healthy volunteers
No

Inclusion criteria

  • 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

Exclusion criteria

Exclusion Criteria:

  • 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
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
138 participants (estimated)

Study arms

  • Experimental
    ARM A: TAilored management

    No steroids at admission Antibiotics - GBS prophylaxis + macrolides always at admission till results of amniotic fluid IL-6 Amniocentesis (Within 24 hours of admission to the hospital) * Based on the amniotic fluid IL-6 results: * IL-6 ˂ 2600 - discontinuing GBS prophylaxis + macrolides, no steroids. * IL-6 ≥ 2600 - Steroids and initial broad spectrum ABX, adjustment according to cultures and PCR

    Procedure: Tailored antibiotic and steroid therapy based on the IL-6 value in amniotic fluid obtained by amniocentesis in patients with premature rupture of membranes · Drug: Antenatal steroids administration · Drug: Neuroprotection · Drug: antibiotic prophylaxis

  • Active comparator
    ARM B: standard care

    Antenatal steroids - always at admission Antibiotics - GBS prophylaxis + macrolides, lasting for 7-10days, then discontinued.

    Drug: Antenatal steroids administration · Drug: Neuroprotection · Drug: antibiotic prophylaxis · Drug: Antibiotics administration

Interventions

  • ProcedureTailored 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.

    Also known as: amniocentesis

  • DrugAntenatal 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 single course prior 34+0 if at least 7 days have passed after the previous course) and tocolysis

  • DrugNeuroprotection

    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.

  • Drugantibiotic prophylaxis

    Antibiotics - Group B Streptococcus (GBS) prophylaxis + macrolides, always at admission.

  • DrugAntibiotics 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: Vancomycin 1g IV every 12 h or Clindamycin 600-900g IV every 8h taking antibiotic sensitivity into account. Before administering the third dose of gentamicin, its serum level should be determined (at a level \>4 umol/l, the dose must be reduced).

05

What researchers measure

Primary outcomes

  1. The latency of pregnancy of more than 7 days from premature rupture of membranes to delivery

    Latency ˃ 7d is an outcome traditionally used in trials studying pPROM and PTB.

    Time frame: From enrollment to the delivery (0-98 days).

Secondary outcomes

  1. Latency to birth

    Time frame: Measured in days from pPROM to birth (0-98 days).

  2. Incidence of chorioamnionitis and funisitis

    Diagnosed during pregnancy based on clinical criteria or postpartum based on histological examination of placenta and umbilical cord.

    Time frame: From the enrollment to the delivery (0-98 days).

  3. Short-term adverse maternal outcomes

    List of short-term adverse maternal outcomes: 1. mortality 2. infection complication: sepsis, endometritis, wound infection, endometritis 3. postpartum haemorrhage 4. postpartum hysterectomy 5. admission to the maternal intensive care unit 6. unplanned operative procedure after delivery (dilation and curettage, laparoscopy, or laparotomy) 7. injury requiring repair 8. uterine rupture 9. haemorrhage of \>1000 mL 10. transfusion 11. acute renal insufficiency 12. venous thromboembolism 13. pulmonary embolism 14. readmission to the hospital within 6 weeks

    Time frame: From the enrollment to the 6 weeks postpartum. Time from enrollment to delivery is 0-14 weeks. Time frame ranges from 0-20 weeks.

  4. Short-term neonatal outcomes

    List of short-term neonatal outcomes: 1. mortality 2. gestational week at birth, birth weight and weight percentile 3. status of antenatal steroids (expired/complete/incomplete) 4. umbilical cord pH 5. IL-6 from the umbilical cord 6. Apgar score at 1 and 5 minutes 7. need of intubation of the neonate after birth 8. surfactant application 9. days on ventilator 10. the length of non-invasive respiratory support (postmenstrual week) 11. the need for home oxygen therapy 12. early pulmonary hypertension with iNO (Inhaled nitric oxide) 13. patent ductus arteriosus (PDA) over 14 days over 1.5 mm/ ligation/ left ventricular outflow (LVO) over 450 ml/kg/min in 14 days) 14. intraventricular haemorrhage (IVH) stage III-IV or periventricular leukomalacia (PVL) or other severe injury of brain visible on ultrasound 15. bronchopulmonary dysplasia (BPD) stage II and III (Jensen) 16. retinopathy of newborn (ROP) requiring invasive treatment 17. necrotizing enterocolitis (NEC) with need of surgical so

    Time frame: From the birth to 6-months postpartum.

Other outcomes

  1. Microbiome in mother and newborn

    Microbiome sequencing based on the bucal and rectal swabs.

    Time frame: Samples collected immediatelly after delivery.

06

Study locations

3 of 3 sites recruiting
  • University Hospital Brno
    Brno, Czechia
    Recruiting
  • General University Hospital in Prague
    Prague, 128 08, Czechia
    Recruiting
  • Institute for Mother and Child Care in Prague - Podolí
    Prague, Czechia
    • Hynek Heřman, MD, Ph.D., LL.M., MHA · Contact · info@upmd.eu · +420296511111
    Recruiting
07

References and documents

Publications

  • 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. PubMed 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. PubMed 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. PubMed 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. PubMed 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. PubMed 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. PubMed 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. PubMed 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. PubMed 18177778 ↗
  • Mercer BM, Crouse DT, Goldenberg RL, Miodovnik M, Mapp DC, Meis PJ, Dombrowski MP; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. The antibiotic treatment of PPROM study: systemic maternal and fetal markers and perinatal outcomes. Am J Obstet Gynecol. 2012 Feb;206(2):145.e1-9. doi: 10.1016/j.ajog.2011.08.028. Epub 2011 Sep 8. PubMed 22000668 ↗
  • Garg A, Jaiswal A. Evaluation and Management of Premature Rupture of Membranes: A Review Article. Cureus. 2023 Mar 24;15(3):e36615. doi: 10.7759/cureus.36615. eCollection 2023 Mar. PubMed 37155446 ↗
  • Boettcher LB, Clark EAS. Neonatal and Childhood Outcomes Following Preterm Premature Rupture of Membranes. Obstet Gynecol Clin North Am. 2020 Dec;47(4):671-680. doi: 10.1016/j.ogc.2020.09.001. Epub 2020 Oct 7. PubMed 33121652 ↗
  • Prelabor Rupture of Membranes: ACOG Practice Bulletin, Number 217. Obstet Gynecol. 2020 Mar;135(3):e80-e97. doi: 10.1097/AOG.0000000000003700. PubMed 32080050 ↗

Individual participant data

Plan to share: Undecided — Only IPD used in the results publication

08

Registry details

Key details

Study ID
NCT07107477
Lead sponsor
The Central and Eastern European Gynecologic Oncology Group
Collaborators
Brno University Hospital, General University Hospital, Prague
Responsible party
David Cibula (Prof. Dr., General University Hospital, Prague) — Principal investigator
First posted
Aug 6, 2025
Start date
May 1, 2025
Primary completion
Sep 1, 2027 (estimated)
Completion
May 1, 2028 (estimated)
Last update
Jun 18, 2026

Study contacts

Katerina Mackova, MD, PhD, PhD
Contact
katerina.mackova@vfn.cz
+420733253563
Martina Boricnova, PhD
Contact
martina.borcinova@vfn.cz
+420736122654

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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