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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:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
|
| 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) |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Jagdeesh Kaur Kaur, Medical Degree | Contact | +6 0122129958 | jagdeesh_kaur@hotmail.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sarawak General Hospital | Kuching | Sarawak | 93586 | Malaysia |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 8879841 | Background | 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. | |
| 36464667 | Background |
| Label | URL |
|---|---|
| Malaysia's National Antibiotics Guidelines | View source |
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Individual participant data will not be shared because there is currently no formal data-sharing plan or repository arrangement for this investigator-initiated study.
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| ID | Term |
|---|---|
| D005322 | Fetal Membranes, Premature Rupture |
| D000071074 | Neonatal Sepsis |
| ID | Term |
|---|---|
| D007744 | Obstetric Labor Complications |
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
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| ID | Term |
|---|---|
| D000667 | Ampicillin |
| D005839 | Gentamicins |
| ID | Term |
|---|---|
| D010400 | Penicillin G |
| D010406 | Penicillins |
| D047090 | beta-Lactams |
| D007769 | Lactams |
| D000577 |
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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.
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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.
| 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. |
|
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 |
| Miri Hospital | Miri | Sarawak | 98000 | Malaysia |
|
| Sarikei Hospital | Sarikei | Sarawak | 96100 | Malaysia |
|
| 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. |
| 26819787 | 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. |
| 34343185 | 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. |
| 24141714 | 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. |
| 11168913 | 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. |
| 9376915 | 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. |
| 32847438 | 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. |
| 9580172 | 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. |
| 8598837 | 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. |
| 35438865 | 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/ |
| 28742677 | Background | Committee Opinion No. 712: Intrapartum Management of Intraamniotic Infection. Obstet Gynecol. 2017 Aug;130(2):e95-e101. doi: 10.1097/AOG.0000000000002236. |
| 40086563 | 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. |
| D018805 | Sepsis |
| D007239 | Infections |
| D007232 | Infant, Newborn, Diseases |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| Amides |
| D009930 | Organic Chemicals |
| D013457 | Sulfur Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |