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

NCT07563504 | Not Yet Recruiting Phase 4

• 1 other identifier: PROMab-2026-01
• Study Type: interventional
• Target: 320
• Locations: 1 country
• Sites: 3

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. 1.undergo screening and eligibility assessment
2. 2.provide written informed consent before randomisation
3. 3.be randomly assigned to receive either intravenous ampicillin alone or intravenous ampicillin plus gentamicin
4. 4.start study antibiotics at 12 hours after membrane rupture and continue treatment until delivery
5. 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. 6.optionally consent to placental tissue collection for microbiological culture at delivery

Conditions

Rupture of Membranes Prior to Onset of Labor

Keywords

Term PROM (Prelabour Rupture of Membranes); Intrapartum Antibiotic Prophylaxis; Ampicillin; Gentamicin; Clinical Chorioamnionitis; Maternal Infection; Neonatal Sepsis; Randomized Controlled Trial

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (15)

• Intrapartum Maternal Fever

  From admission (diagnosis of PROM) until delivery (72 hours)

• Postpartum Fever During Index Admission

  From admission (diagnosis of PROM) until delivery 7 days postpartum

• Early Postpartum Endometritis During Index Admission

  From admission (diagnosis of PROM) until delivery 7 days postpartum

• Peripartum Infection During Index Admission

  From admission (diagnosis of PROM) until delivery 7 days postpartum

• Postpartum Antibiotic Treatment Exceeding 24 Hours

  From admission (diagnosis of PROM) until delivery 7 days postpartum

Study Arms (2)

Ampicillin Alone

ACTIVE COMPARATOR

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

Ampicillin Plus Gentamicin

EXPERIMENTAL

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

Interventions

Ampicillin DRUG

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.

Ampicillin Alone

Ampicillin + gentamicin DRUG

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.

Ampicillin Plus Gentamicin

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sarawak General Hospital: lead

Study Sites (3)

Sarawak General Hospital

Kuching, Sarawak, 93586, Malaysia

Location

Miri Hospital

Miri, Sarawak, 98000, Malaysia

Location

Sarikei Hospital

Sarikei, Sarawak, 96100, Malaysia

Location

Related Publications (13)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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.

  PMID: 9580172 BACKGROUND

• 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.

  PMID: 8598837 BACKGROUND

• Inducing labour. London: National Institute for Health and Care Excellence (NICE); 2021 Nov 4. Available from http://www.ncbi.nlm.nih.gov/books/NBK579537/

  PMID: 35438865 BACKGROUND

• Committee Opinion No. 712: Intrapartum Management of Intraamniotic Infection. Obstet Gynecol. 2017 Aug;130(2):e95-e101. doi: 10.1097/AOG.0000000000002236.

  PMID: 28742677 BACKGROUND

• 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.

  PMID: 40086563 BACKGROUND

Related Links

• Malaysia's National Antibiotics Guidelines

MeSH Terms

Conditions

Fetal Membranes, Premature Rupture; Neonatal Sepsis

Interventions

Ampicillin; Gentamicins

Condition Hierarchy (Ancestors)

Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Sepsis; Infections; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Penicillin G; Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Central Study Contacts

Jagdeesh Kaur Kaur, Medical Degree

CONTACT

+6 0122129958; jagdeesh_kaur@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: 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.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Obstetrics and Gynaecology Specialist, Maternal-Fetal Medicine Fellow

Model Details: 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.

Study Record Dates

• First Submitted: April 16, 2026
• First Posted: May 4, 2026
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): March 31, 2027
• Last Updated: May 4, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

MY (3)