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

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.

Conditions

• Preterm Premature Rupture of Membranes (PPROM)

Interventions

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

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.

DRUG

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

DRUG

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.

DRUG

antibiotic prophylaxis

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

DRUG

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: 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).

Sponsors & Collaborators

• University Hospital Brno

  collaborator UNKNOWN

• General University Hospital, Prague

  collaborator OTHER

• The Central and Eastern European Gynecologic Oncology Group

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-05-01

Primary Completion

2027-09-01

Completion

2028-05-01

Countries

• Czechia

Study Locations