Preterm Premature Rupture of Membranes (PPROM)
Conditions
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: 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.
Interventions
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.
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.
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
DRUGantibiotic prophylaxis
Antibiotics - Group B Streptococcus (GBS) prophylaxis + macrolides, always at admission.
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
The Central and Eastern European Gynecologic Oncology Group
Brno University Hospital
General University Hospital, Prague
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
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
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The latency of pregnancy of more than 7 days from premature rupture of membranes to delivery | From enrollment to the delivery (0-98 days). | Latency ˃ 7d is an outcome traditionally used in trials studying pPROM and PTB. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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). | Diagnosed during pregnancy based on clinical criteria or postpartum based on histological examination of placenta and umbilical cord. |
| 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. | 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 |
| Short-term neonatal outcomes | From the birth to 6-months postpartum. | 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 |
Countries
Czechia
Contacts
CONTACTKaterina Mackova, MD, PhD, PhD
CONTACTMartina Boricnova, PhD
Outcome results
None listed