PROMab Trial: Ampicillin With or Without Gentamicin for Term Prelabour Rupture of Membranes

Official title

Term Prelabour Rupture of Membranes Antibiotic Prophylaxis (PROMab) Trial

Overview

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

• Drug Ampicillin
  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.
• Drug Ampicillin + gentamicin
  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.

Primary outcome measures

• Clinical Chorioamnionitis [Time frame: From admission (diagnosis of PROM) until delivery (72 hours)]

Secondary outcome measures (12)

• Intrapartum Maternal Fever [Time frame: From admission (diagnosis of PROM) until delivery (72 hours)]
• Postpartum Fever During Index Admission [Time frame: From admission (diagnosis of PROM) until delivery 7 days postpartum]
• Early Postpartum Endometritis During Index Admission [Time frame: From admission (diagnosis of PROM) until delivery 7 days postpartum]
• Peripartum Infection During Index Admission [Time frame: From admission (diagnosis of PROM) until delivery 7 days postpartum]
• Postpartum Antibiotic Treatment Exceeding 24 Hours [Time frame: From admission (diagnosis of PROM) until delivery 7 days postpartum]
• Puerperal Endometritis After Discharge [Time frame: From discharge until 42 days postpartum.]
• Wound Infection [Time frame: From delivery until 42 days postpartum.]
• Infection-related Hospitalisation Longer Than 5 Days or Readmission for Infection [Time frame: From delivery until 42 days postpartum.]
• Culture-proven Early-onset Neonatal Sepsis [Time frame: Within the first 72 hours of life]
• Neonatal Sepsis Evaluation [Time frame: From birth till 7 days of life]
• NICU Admission [Time frame: From birth till 7 days of life]
• Composite Neonatal Adverse Outcome [Time frame: From birth till 7 days of life]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Prevention

Study locations

Malaysia · 3 centers

• Sarawak General Hospital — Kuching
• Miri Hospital — Miri
• Sarikei Hospital — Sarikei

Publications

• Rutanen EM, Karkkainen TH, Lehtovirta J, Uotila JT, Hinkula MK, Hartikainen AL. Evaluation of a rapid strip test for insulin-like growth factor binding protein-1 in the diagnosis of ruptured fetal membranes. Clin Chim Acta. 1996 Sep 30;253(1-2):91-101. doi: 10.1016/0009-8981(96)80001-e. PMID 8879841
• Abu Shqara R, Bussidan S, Glikman D, Rechnitzer H, Lowenstein L, Frank Wolf M. Clinical implications of uterine cultures obtained during urgent caesarean section. Aust N Z J Obstet Gynaecol. 2023 Jun;63(3):344-351. doi: 10.1111/ajo.13630. Epub 2022 Dec 4. PMID 36464667
• Montelongo EM, Blue NR, Lee RH. Placenta Accreta in a Woman with Escherichia coli Chorioamnionitis with Intact Membranes. Case Rep Obstet Gynecol. 2015;2015:121864. doi: 10.1155/2015/121864. Epub 2015 Dec 27. PMID 26819787
• Solomon S, Akeju O, Odumade OA, Ambachew R, Gebreyohannes Z, Van Wickle K, Abayneh M, Metaferia G, Carvalho MJ, Thomson K, Sands K, Walsh TR, Milton R, Goddard FGB, Bekele D, Chan GJ. Prevalence and risk factors for antimicrobial resistance among newborns with gram-negative sepsis. PLoS One. 2021 Aug 3;16(8):e0255410. doi: 10.1371/journal.pone.0255410. eCollection 2021. PMID 34343185
• World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013 Nov 27;310(20):2191-4. doi: 10.1001/jama.2013.281053. No abstract available. PMID 24141714
• Santschi EM, Papich MG. Pharmacokinetics of gentamicin in mares in late pregnancy and early lactation. J Vet Pharmacol Ther. 2000 Dec;23(6):359-63. doi: 10.1046/j.1365-2885.2000.00298.x. PMID 11168913
• Gribomont AC, Stragier A. [Idiopathic epimacular membrane and vitreo-macular traction syndrome: vitrectomy functional results]. Bull Soc Belge Ophtalmol. 1996;262:123-6. French. PMID 9376915
• Senat MV, Schmitz T, Bouchghoul H, Diguisto C, Girault A, Paysant S, Sibiude J, Lassel L, Sentilhes L. Term prelabor rupture of membranes: guidelines for clinical practice from the French College of Gynaecologists and Obstetricians (CNGOF). J Matern Fetal Neonatal Med. 2022 Aug;35(16):3105-3109. doi: 10.1080/14767058.2020.1810230. Epub 2020 Aug 27. PMID 32847438

Identifiers

NCT: NCT07563504 · PROMab-2026-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗