Rupture of Membranes Prior to Onset of Labor
Conditions
Keywords
Term PROM (Prelabour Rupture of Membranes), Intrapartum Antibiotic Prophylaxis, Ampicillin, Gentamicin, Clinical Chorioamnionitis, Maternal Infection, Neonatal Sepsis, Randomized Controlled Trial
Brief summary
The goal of this clinical trial is to learn whether adding gentamicin to standard ampicillin prophylaxis can better prevent clinical chorioamnionitis and other maternal and neonatal infectious complications in pregnant women aged 18 years or older with singleton, cephalic, term pregnancies and confirmed prelabour rupture of membranes. The main questions it aims to answer are: Does ampicillin plus gentamicin reduce the incidence of clinical chorioamnionitis compared with ampicillin alone? Does ampicillin plus gentamicin improve maternal infectious outcomes and neonatal infection-related outcomes compared with ampicillin alone? Researchers will compare ampicillin alone with ampicillin plus gentamicin to see whether broader antibiotic coverage reduces maternal and neonatal infectious morbidity. Participants will: 1. undergo screening and eligibility assessment 2. provide written informed consent before randomisation 3. be randomly assigned to receive either intravenous ampicillin alone or intravenous ampicillin plus gentamicin 4. start study antibiotics at 12 hours after membrane rupture and continue treatment until delivery 5. undergo routine maternal and fetal monitoring during labour and delivery have maternal and neonatal outcomes assessed during hospital stay and up to 42 days postpartum, including telephone follow-up at Day 14 and Day 42 6. optionally consent to placental tissue collection for microbiological culture at delivery
Interventions
DRUGAmpicillin
Intravenous ampicillin 2 g stat, followed by 1 g every 4 hours, initiated at 12 hours after prelabour rupture of membranes and continued until delivery.
Intravenous ampicillin 2 g stat, followed by intravenous ampicillin 1 g every 4 hours, plus intravenous gentamicin 5 mg/kg once daily. Study antibiotics will be initiated at 12 hours after prelabour rupture of membranes and continued until delivery. Gentamicin will only be administered to participants with baseline creatinine clearance of 30 mL/min or higher.
Sponsors
Sarawak General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Masking description
Participants will be blinded to treatment allocation. Treating clinicians and investigators will not be blinded because of weight-based gentamicin dosing, operational differences between antibiotic regimens, and the requirement for baseline renal function assessment prior to gentamicin administration.
Intervention model description
Participants with term prelabour rupture of membranes will be randomized in a 1:1 ratio to one of two parallel groups: intravenous ampicillin alone or intravenous ampicillin plus gentamicin. Study antibiotics will be initiated at 12 hours after membrane rupture and continued until delivery.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 18 years or older * Singleton pregnancy * Cephalic (vertex) presentation * Term gestation of 37+0 weeks or more based on obstetric dating * Confirmed prelabour rupture of membranes * Duration of prelabour rupture of membranes 12 hours or less at the time of enrolment * Unknown or negative Group B Streptococcus status in the current pregnancy * Clear amniotic fluid at presentation * Afebrile with no clinical signs of intra-amniotic infection at admission * Able to provide written informed consent * Planned delivery at a participating study hospital
Exclusion criteria
* Preterm prelabour rupture of membranes before 37+0 weeks * Fever of 38.0°C or higher, maternal tachycardia, uterine tenderness, purulent discharge, or other clinical suspicion of infection at admission * Antibiotics already initiated in the current episode of care for any reason * Receipt of systemic antibiotics in the past 7 days * Meconium-stained liquor at presentation * Contraindication to vaginal delivery, including malpresentation, major placenta praevia, maternal refusal of trial of labour after caesarean, or known absolute indication for elective lower segment caesarean section * Known Group B Streptococcus colonisation in the current pregnancy, including positive rectovaginal swab or bacteriuria * Abnormal cardiotocography on admission requiring expedited delivery * Allergy or contraindication to penicillin or aminoglycosides * Renal impairment defined as creatinine clearance less than 30 mL/min * Known renal disease * Known ototoxicity risk or vestibular/cochlear disorders * Unknown timing of prelabour rupture of membranes * Multiple gestation * Major fetal anomaly
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Chorioamnionitis | From admission (diagnosis of PROM) until delivery (72 hours) | Incidence of clinical chorioamnionitis, defined as maternal temperature ≥39.0°C once, or maternal temperature 38.0-38.9°C plus at least one of the following: leukocytosis \>15,000/mm³, purulent cervical or vaginal discharge, fetal tachycardia (baseline fetal heart rate \>160 bpm for ≥10 minutes), or malodorous liquor. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Intrapartum Maternal Fever | From admission (diagnosis of PROM) until delivery (72 hours) | Incidence of intrapartum maternal fever, defined as axillary temperature ≥38.0°C on a single reading, or ≥37.5°C on two readings at least 1 hour apart during labour. |
| Postpartum Fever During Index Admission | From admission (diagnosis of PROM) until delivery 7 days postpartum | Incidence of postpartum fever, defined as axillary temperature ≥38.0°C recorded at any time after delivery until discharge during the index hospital admission. |
| Early Postpartum Endometritis During Index Admission | From admission (diagnosis of PROM) until delivery 7 days postpartum | Incidence of early postpartum endometritis diagnosed during the index hospital admission, defined as axillary temperature ≥38.0°C in the absence of an alternative identifiable cause and at least one associated clinical feature, including uterine tenderness, purulent or foul-smelling lochia, maternal tachycardia, or lower abdominal or uterine pain. |
| Peripartum Infection During Index Admission | From admission (diagnosis of PROM) until delivery 7 days postpartum | Incidence of peripartum infection, defined as the occurrence of clinical chorioamnionitis and/or early postpartum endometritis during the same hospital admission. |
| Postpartum Antibiotic Treatment Exceeding 24 Hours | From admission (diagnosis of PROM) until delivery 7 days postpartum | Incidence of systemic antibiotic therapy continued for more than 24 hours after delivery during the index hospital admission for suspected or confirmed infection, excluding routine single-dose perioperative prophylaxis for caesarean section. |
| Puerperal Endometritis After Discharge | From discharge until 42 days postpartum. | Incidence of puerperal endometritis diagnosed after hospital discharge and up to 42 days postpartum, based on clinical documentation and/or requirement for antibiotic treatment for endometritis. |
| Wound Infection | From delivery until 42 days postpartum. | Incidence of wound infection involving the caesarean section wound and/or perineal wound or episiotomy within 42 days postpartum, as evidenced by clinical diagnosis and/or treatment such as antibiotics, wound drainage, opening, or debridement. |
| Infection-related Hospitalisation Longer Than 5 Days or Readmission for Infection | From delivery until 42 days postpartum. | Incidence of infection-related hospitalisation longer than 5 days during the index admission and/or hospital readmission within 42 days postpartum with a primary diagnosis of infection and/or requiring systemic antibiotic therapy |
| Culture-proven Early-onset Neonatal Sepsis | Within the first 72 hours of life | Incidence of culture-proven early-onset neonatal sepsis, defined as isolation of a pathogenic organism from blood and/or cerebrospinal fluid culture, with clinical features consistent with infection. |
| Neonatal Sepsis Evaluation | From birth till 7 days of life | Incidence of neonatal sepsis evaluation, defined as performance of a neonatal septic work-up including one or more of the following: blood culture, full blood count, or other investigations performed as part of routine neonatal sepsis assessment. |
| NICU Admission | From birth till 7 days of life | Incidence of admission to the neonatal intensive care unit at any time during the neonatal hospital stay, for any indication. |
| Composite Neonatal Adverse Outcome | From birth till 7 days of life | Incidence of a composite neonatal adverse outcome defined as the occurrence of one or more of the following: requirement for ventilator support, tachypnoea with or without oxygen supplementation persisting beyond 6 hours of life, temperature instability requiring clinical intervention, or requirement for second-line antibiotics. |
| Presumed Early-onset Neonatal Sepsis | From birth till 7 days of life. | Incidence of presumed early-onset neonatal sepsis, defined as culture-negative infants who receive at least 5 days of intravenous antibiotics based on clinical assessment, with or without supportive laboratory findings, as determined by the neonatal team. |
| Infection-related Neonatal Hospitalisation Longer Than 5 Days or Readmission | From birth until 42 days of life. | Incidence of neonatal hospitalisation longer than 5 days primarily attributed to suspected or confirmed infection and/or readmission within 42 days of life with a primary diagnosis of infection and/or requiring intravenous antibiotic therapy. |
| Placental Chorioamniotic Tissue Culture | At delivery | Placental chorioamniotic tissue culture results obtained at delivery and categorized into predefined microbiological groups, including Enterobacteriaceae, Group B Streptococcus, anaerobes, Enterococcus faecalis, and negative cultures. |
Countries
Malaysia
Contacts
CONTACTJagdeesh Kaur Kaur, Medical Degree
Outcome results
None listed