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

Term Prelabour Rupture of Membranes Antibiotic Prophylaxis (PROMab) Trial

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

Study Overview

• Status: Not yet recruiting
• Conditions: Rupture of Membranes Prior to Onset of Labor
• Intervention / Treatment: Drug: Ampicillin; Drug: Ampicillin + gentamicin

• Study Type: Interventional
• Enrollment (Estimated): 320
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jagdeesh Kaur Kaur, Medical Degree; Phone Number: +6 0122129958; Email: jagdeesh_kaur@hotmail.com

Study Locations

• Malaysia
  • Sarawak
    • Kuching, Sarawak, Malaysia, 93586
      • Sarawak General Hospital
      • Contact: Jagdeesh Kaur, Medical Degree; Phone Number: +6 0122129958; Email: jagdeesh_kaur@hotmail.com
      • Contact: Yan Hian Voon, Medical Degree; Phone Number: +6 0162317072; Email: vhaxyn@gmail.com
    • Miri, Sarawak, Malaysia, 98000
      • Miri Hospital
      • Contact: Shan Pau Foong, Medical Degree; Phone Number: +6 0189071927; Email: mushroomatwork@gmail.com
    • Sarikei, Sarawak, Malaysia, 96100
      • Sarikei Hospital
      • Contact: Cheng Ming Chai, Medical Degree; Phone Number: +6 0168709882; Email: mingcheng.cmc@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ampicillin Alone; Participants randomized to this arm will receive intravenous ampicillin 2 g stat, followed by intravenous ampicillin 1 g every 4 hours. Study antibiotics will be initiated at 12 hours after prelabour rupture of membranes and continued until delivery. If clinical chorioamnionitis develops, study prophylaxis will be discontinued and therapeutic antibiotics will be started according to local hospital protocol.	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.
Experimental: Ampicillin Plus Gentamicin; Participants randomized to this arm will receive 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. If clinical chorioamnionitis develops, study prophylaxis will be discontinued and therapeutic antibiotics will be started according to local hospital protocol	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Chorioamnionitis	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.	From admission (diagnosis of PROM) until delivery (72 hours)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intrapartum Maternal Fever	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.	From admission (diagnosis of PROM) until delivery (72 hours)
Postpartum Fever During Index Admission	Incidence of postpartum fever, defined as axillary temperature ≥38.0°C recorded at any time after delivery until discharge during the index hospital admission.	From admission (diagnosis of PROM) until delivery 7 days postpartum
Early Postpartum Endometritis During Index Admission	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.	From admission (diagnosis of PROM) until delivery 7 days postpartum
Peripartum Infection During Index Admission	Incidence of peripartum infection, defined as the occurrence of clinical chorioamnionitis and/or early postpartum endometritis during the same hospital admission.	From admission (diagnosis of PROM) until delivery 7 days postpartum
Postpartum Antibiotic Treatment Exceeding 24 Hours	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.	From admission (diagnosis of PROM) until delivery 7 days postpartum
Puerperal Endometritis After Discharge	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.	From discharge until 42 days postpartum.
Wound Infection	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.	From delivery until 42 days postpartum.
Infection-related Hospitalisation Longer Than 5 Days or Readmission for Infection	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	From delivery until 42 days postpartum.
Culture-proven Early-onset Neonatal Sepsis	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.	Within the first 72 hours of life
Neonatal Sepsis Evaluation	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.	From birth till 7 days of life
NICU Admission	Incidence of admission to the neonatal intensive care unit at any time during the neonatal hospital stay, for any indication.	From birth till 7 days of life
Composite Neonatal Adverse Outcome	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.	From birth till 7 days of life
Presumed Early-onset Neonatal Sepsis	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.	From birth till 7 days of life.
Infection-related Neonatal Hospitalisation Longer Than 5 Days or Readmission	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.	From birth until 42 days of life.
Placental Chorioamniotic Tissue Culture	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.	At delivery

Collaborators and Investigators

• Sponsor: Sarawak General Hospital

Publications and helpful links

General Publications

• 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.
• Hannah ME, Ohlsson A, Farine D, Hewson SA, Hodnett ED, Myhr TL, Wang EE, Weston JA, Willan AR. Induction of labor compared with expectant management for prelabor rupture of the membranes at term. TERMPROM Study Group. N Engl J Med. 1996 Apr 18;334(16):1005-10. doi: 10.1056/NEJM199604183341601.
• Committee Opinion No. 712: Intrapartum Management of Intraamniotic Infection. Obstet Gynecol. 2017 Aug;130(2):e95-e101. doi: 10.1097/AOG.0000000000002236.
• 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.
• 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.
• 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.
• 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.
• 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.
• Gribomont AC, Stragier A. [Idiopathic epimacular membrane and vitreo-macular traction syndrome: vitrectomy functional results]. Bull Soc Belge Ophtalmol. 1996;262:123-6. French.
• 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.
• Cararach V, Botet F, Sentis J, Almirall R, Perez-Picanol E. Administration of antibiotics to patients with rupture of membranes at term: a prospective, randomized, multicentric study. Collaborative Group on PROM. Acta Obstet Gynecol Scand. 1998 Mar;77(3):298-302.
• Inducing labour. London: National Institute for Health and Care Excellence (NICE); 2021 Nov 4. Available from http://www.ncbi.nlm.nih.gov/books/NBK579537/
• Abu Shqara R, Glikman D, Goldinfeld G, Braude O, Assy S, Hassan D, Sgayer I, Ganem N, Shasha-Lavsky H, Yefet E, Matanis M, Lowenstein L, Frank Wolf M. Ampicillin and gentamicin prophylaxis is superior to ampicillin alone in patients with prelabor rupture of membranes at term: the results of a randomized clinical trial. Am J Obstet Gynecol. 2025 Oct;233(4):321.e1-321.e10. doi: 10.1016/j.ajog.2025.03.011. Epub 2025 Mar 12.

Helpful Links

• Malaysia's National Antibiotics Guidelines

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): March 31, 2027

Study Registration Dates

• First Submitted: April 16, 2026
• First Submitted That Met QC Criteria: April 25, 2026
• First Posted (Actual): May 4, 2026

Study Record Updates

• Last Update Posted (Actual): May 4, 2026
• Last Update Submitted That Met QC Criteria: April 25, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Ampicillin; Randomized Controlled Trial; Gentamicin; Neonatal Sepsis; Intrapartum Antibiotic Prophylaxis; Term PROM (Prelabour Rupture of Membranes); Clinical Chorioamnionitis; Maternal Infection
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Female Urogenital Diseases and Pregnancy Complications; Obstetric Labor Complications; Pregnancy Complications; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Neonatal Sepsis; Fetal Membranes, Premature Rupture; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Carbohydrates; Glycosides; Amides; Aminoglycosides; Penicillin G; beta-Lactams; Lactams; Penicillins; Ampicillin; Gentamicins
• Other Study ID Numbers: PROMab-2026-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared because there is currently no formal data-sharing plan or repository arrangement for this investigator-initiated study.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No