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

NCT07107477 | Recruiting Phase 3 DMC

• 1 other identifier: TAILORED-PROM 2024-520237-77-0
• Study Type: interventional
• Target: 138
• Locations: 1 country
• Sites: 3

Brief 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:

• 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.

Conditions

Preterm Premature Rupture of Membranes (PPROM)

Outcome Measures

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.

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

Secondary Outcomes (4)

• Latency to birth

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

• Incidence of chorioamnionitis and funisitis

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

• Short-term adverse maternal outcomes

  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

  From the birth to 6-months postpartum.

Other Outcomes (1)

• Microbiome in mother and newborn

  Samples collected immediatelly after delivery.

Study Arms (2)

ARM A: TAilored management

EXPERIMENTAL

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

ARM B: standard care

ACTIVE COMPARATOR

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

Antenatal steroids administration DRUG

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

ARM A: TAilored management; ARM B: standard care

Tailored antibiotic and steroid therapy based on the IL-6 value in amniotic fluid obtained by amniocentesis in patients with premature rupture of membranes PROCEDURE

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

ARM A: TAilored management

Neuroprotection DRUG

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.

ARM A: TAilored management; ARM B: standard care

antibiotic prophylaxis DRUG

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

ARM A: TAilored management; ARM B: standard care

Antibiotics administration DRUG

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).

ARM B: standard care

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• The Central and Eastern European Gynecologic Oncology Group: lead
• Brno University Hospital: collaborator
• General University Hospital, Prague: collaborator

Study Sites (3)

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

RECRUITING

Related Publications (12)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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.

  PMID: 22000668 BACKGROUND

• 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.

  PMID: 37155446 BACKGROUND

• 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.

  PMID: 33121652 BACKGROUND

• Prelabor Rupture of Membranes: ACOG Practice Bulletin, Number 217. Obstet Gynecol. 2020 Mar;135(3):e80-e97. doi: 10.1097/AOG.0000000000003700.

  PMID: 32080050 BACKGROUND

MeSH Terms

Conditions

Preterm Premature Rupture of the Membranes

Interventions

Amniocentesis; Neuroprotection; Antibiotic Prophylaxis

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Paracentesis; Specimen Handling; Prenatal Diagnosis; Diagnostic Techniques, Obstetrical and Gynecological; Punctures; Surgical Procedures, Operative; Investigative Techniques; Nervous System Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Chemoprevention; Drug Therapy; Therapeutics; Premedication

Central Study Contacts

Katerina Mackova, MD, PhD, PhD

CONTACT

+420733253563; katerina.mackova@vfn.cz

Martina Boricnova, PhD

CONTACT

+420736122654; martina.borcinova@vfn.cz

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr.

Study Record Dates

• First Submitted: July 22, 2025
• First Posted: August 6, 2025
• Study Start: May 1, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): May 1, 2028
• Last Updated: June 18, 2026

Record last verified: 2026-06

Locations

CZ (3)