Ignite Creation Date:
2025-12-24 @ 3:33 PM
Ignite Modification Date:
2025-12-25 @ 10:51 PM
Study NCT ID:
NCT04762992
Status:
ENROLLING_BY_INVITATION
Last Update Posted:
2025-08-13
First Post:
2021-02-17
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
LMWH for Treatment of Early Fetal Growth Restriction (HepaGrowth)
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D005317', 'term': 'Fetal Growth Retardation'}, {'id': 'D047928', 'term': 'Premature Birth'}, {'id': 'D011225', 'term': 'Pre-Eclampsia'}], 'ancestors': [{'id': 'D005315', 'term': 'Fetal Diseases'}, {'id': 'D011248', 'term': 'Pregnancy Complications'}, {'id': 'D005261', 'term': 'Female Urogenital Diseases and Pregnancy Complications'}, {'id': 'D000091642', 'term': 'Urogenital Diseases'}, {'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}, {'id': 'D006130', 'term': 'Growth Disorders'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D007752', 'term': 'Obstetric Labor, Premature'}, {'id': 'D007744', 'term': 'Obstetric Labor Complications'}, {'id': 'D046110', 'term': 'Hypertension, Pregnancy-Induced'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D059039', 'term': 'Standard of Care'}], 'ancestors': [{'id': 'D019984', 'term': 'Quality Indicators, Health Care'}, {'id': 'D011787', 'term': 'Quality of Health Care'}, {'id': 'D006298', 'term': 'Health Services Administration'}, {'id': 'D017530', 'term': 'Health Care Quality, Access, and Evaluation'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'DOUBLE', 'whoMasked': ['CARE_PROVIDER', 'OUTCOMES_ASSESSOR'], 'maskingDescription': 'Blinded to clinicians performing the ultrasound and outcomes assessor'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'pharmacological intervention and standard of care arms'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 12}}, 'statusModule': {'overallStatus': 'ENROLLING_BY_INVITATION', 'startDateStruct': {'date': '2022-07-18', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-03', 'completionDateStruct': {'date': '2026-12-30', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-08-07', 'studyFirstSubmitDate': '2021-02-17', 'studyFirstSubmitQcDate': '2021-02-17', 'lastUpdatePostDateStruct': {'date': '2025-08-13', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2021-02-21', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2026-07-30', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Gestational age at delivery', 'timeFrame': 'day of delivery', 'description': 'Best assessment of the time of gestation, either by first trimester sonography, last menstrual day or day of implantation of in vitro conception product'}], 'secondaryOutcomes': [{'measure': 'Neonatal birtweight and birthweight centile', 'timeFrame': 'day of delivery', 'description': 'Weight at birth of the newborn (in grams) and respective percentile'}, {'measure': 'Newborn Apgar Score in the 5th minute', 'timeFrame': 'day of delivery', 'description': 'Newborn Apgar score in the 5th minute, assessed by a nurse or pediatrician'}, {'measure': 'Newborn Umbilical Artery pH', 'timeFrame': 'day of delivery', 'description': 'pH of the umbilical artery, assessed immediately after delivery'}, {'measure': 'Stillbirth, neonatal intensive care admission and duration of admission', 'timeFrame': 'from randomization up to 1 year after delivery', 'description': 'A composite outcome of severe neonatal morbidity (evidence of one or more of: intraventricular hemorrhage grade 3 or 4; cystic periventricular leukomalacia; chronic lung disease; retinopathy of prematurity requiring treatment; necrotizingenterocolitis requiring surgery'}, {'measure': 'Maternal and fetal Doppler parameters', 'timeFrame': 'from randomization to delivery', 'description': 'Pulsatility index (PI) of the uterine arteries, PI anddiastolic flow in the umbilical artery, PI in the middle cerebral artery, cerebro-placental ratio, ductusvenosus PI and a wave'}, {'measure': 'Placental pathology', 'timeFrame': 'day of delivery', 'description': 'Percentage of placenta occupied by fibrosis or infarcts'}, {'measure': 'Sflt1-PLGF ratio', 'timeFrame': 'from randomization to delivery', 'description': 'Evolution of Sflt1-PLGF ratio from diagnosis of FGR to delivery'}, {'measure': 'Syncytiotrophoblast membrane extracellular vesicles (STB-EV)', 'timeFrame': 'from randomization up to 1 week after delivery', 'description': 'Protein and genetic composition'}, {'measure': 'Gestational hypertension or preeclampsia; placental abruption', 'timeFrame': 'from randomization up to 1 week after delivery', 'description': 'Pregnancy induced hypertension, preeclamspia,HELLP syndrome'}, {'measure': 'Antepartum hemorrhage; maternal thrombocytopenia (platelets < 100 000 x 10 9/L); postpartum hemorrhage', 'timeFrame': 'from randomization up to 1 week after delivery', 'description': 'Hemorrhage, bruising,pain'}, {'measure': 'Mode and indication for delivery', 'timeFrame': 'from randomization up to 48h after delivery', 'description': 'As spontaneous vaginal birth, operative vaginal birth (forceps orvacuum/ventouse), or cesarean section. For induced labor or planned cesarean section, theindication for scheduling the delivery will be documented (e.g., gestational age, maternal or fetalindications). In cases of operative vaginal or cesarean delivery, the indication for intervention willbe specified (e.g., non-reassuring fetal status, labor dystocia).'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Fetal Growth Retardation', 'Prematurity', 'Pre-Eclampsia', 'Placenta'], 'conditions': ['Fetal Growth Retardation', 'Prematurity', 'Pre-Eclampsia']}, 'referencesModule': {'references': [{'pmid': '18652928', 'type': 'BACKGROUND', 'citation': 'Miller J, Turan S, Baschat AA. Fetal growth restriction. Semin Perinatol. 2008 Aug;32(4):274-80. doi: 10.1053/j.semperi.2008.04.010.'}, {'pmid': '28605820', 'type': 'BACKGROUND', 'citation': 'Nardozza LMM, Zamarian ACP, Araujo Junior E. New Definition of Fetal Growth Restriction: Consensus Regarding a Major Obstetric Complication. Rev Bras Ginecol Obstet. 2017 Jul;39(7):315-316. doi: 10.1055/s-0037-1603741. Epub 2017 Jun 12. No abstract available.'}, {'pmid': '7491742', 'type': 'BACKGROUND', 'citation': 'Arbeille P, Maulik D, Fignon A, Stale H, Berson M, Bodard S, Locatelli A. Assessment of the fetal PO2 changes by cerebral and umbilical Doppler on lamb fetuses during acute hypoxia. Ultrasound Med Biol. 1995;21(7):861-70. doi: 10.1016/0301-5629(95)00025-m.'}, {'pmid': '28285426', 'type': 'BACKGROUND', 'citation': 'Nardozza LM, Caetano AC, Zamarian AC, Mazzola JB, Silva CP, Marcal VM, Lobo TF, Peixoto AB, Araujo Junior E. Fetal growth restriction: current knowledge. Arch Gynecol Obstet. 2017 May;295(5):1061-1077. doi: 10.1007/s00404-017-4341-9. Epub 2017 Mar 11.'}, {'pmid': '1268144', 'type': 'BACKGROUND', 'citation': 'Elder MG, Myatt L. Coagulation and fibrinolysis in pregnancies complicated by fetal growth retardation. Br J Obstet Gynaecol. 1976 May;83(5):355-60. doi: 10.1111/j.1471-0528.1976.tb00842.x.'}, {'pmid': '9514130', 'type': 'BACKGROUND', 'citation': 'Bellart J, Gilabert R, Fontcuberta J, Carreras E, Miralles RM, Cabero L. Coagulation and fibrinolytic parameters in normal pregnancy and in pregnancy complicated by intrauterine growth retardation. Am J Perinatol. 1998 Feb;15(2):81-5. doi: 10.1055/s-2007-993903.'}, {'pmid': '7959327', 'type': 'BACKGROUND', 'citation': 'Fuke Y, Aono T, Imai S, Suehara N, Fujita T, Nakayama M. Clinical significance and treatment of massive intervillous fibrin deposition associated with recurrent fetal growth retardation. Gynecol Obstet Invest. 1994;38(1):5-9. doi: 10.1159/000292434.'}, {'pmid': '26002166', 'type': 'BACKGROUND', 'citation': 'Seravalli V, Baschat AA. A uniform management approach to optimize outcome in fetal growth restriction. Obstet Gynecol Clin North Am. 2015 Jun;42(2):275-88. doi: 10.1016/j.ogc.2015.01.005.'}, {'pmid': '7652929', 'type': 'BACKGROUND', 'citation': 'Tyrell DJ, Kilfeather S, Page CP. Therapeutic uses of heparin beyond its traditional role as an anticoagulant. Trends Pharmacol Sci. 1995 Jun;16(6):198-204. doi: 10.1016/s0165-6147(00)89022-7.'}, {'pmid': '7366291', 'type': 'BACKGROUND', 'citation': 'Lewander R, Lunell NO, Nylund L, Sarby B, Thornstrom S. [Uterine-placental blood flow. Method of measurement and clinical use]. Lakartidningen. 1980 Jan 30;77(5):333-4. No abstract available. Swedish.'}, {'pmid': '24864018', 'type': 'BACKGROUND', 'citation': 'Seravalli V, Block-Abraham DM, Turan OM, Doyle LE, Blitzer MG, Baschat AA. Second-trimester prediction of delivery of a small-for-gestational-age neonate: integrating sequential Doppler information, fetal biometry, and maternal characteristics. Prenat Diagn. 2014 Nov;34(11):1037-43. doi: 10.1002/pd.4418. Epub 2014 Jun 11.'}, {'pmid': '17980196', 'type': 'BACKGROUND', 'citation': 'Picklesimer AH, Oepkes D, Moise KJ Jr, Kush ML, Weiner CP, Harman CR, Baschat AA. Determinants of the middle cerebral artery peak systolic velocity in the human fetus. Am J Obstet Gynecol. 2007 Nov;197(5):526.e1-4. doi: 10.1016/j.ajog.2007.04.002.'}, {'pmid': '19951008', 'type': 'RESULT', 'citation': 'Yu YH, Shen LY, Zou H, Wang ZJ, Gong SP. Heparin for patients with growth restricted fetus: a prospective randomized controlled trial. J Matern Fetal Neonatal Med. 2010 Sep;23(9):980-7. doi: 10.3109/14767050903443459.'}, {'pmid': '15733401', 'type': 'RESULT', 'citation': 'Yu YH, Shen LY, Zhong M, Zhang Y, Su GD, Gao YF, Quan S, Zeng L. [Effect of heparin on fetal growth restriction]. Zhonghua Fu Chan Ke Za Zhi. 2004 Dec;39(12):793-6. Chinese.'}]}, 'descriptionModule': {'briefSummary': 'Early fetal growth restriction (FGR) is associated with considerable fetal and neonatal morbimortality. Placental thrombosis, infarcts and hypercoagulability are frequently seen in these pregnancies, suggesting a role for the activation of the coagulation cascade in the genesis of FGR. Patients will be randomized for low-molecular weight heparin or standard of care, and the outcomes of both arms (gestational age at delivery, gestational and fetal morbidity) will be compared.', 'detailedDescription': 'FGR is the second leading cause of perinatal mortality, being associated with approximately 30% of stillbirths. Early FGR is associated with substantial disturbances of placental implantation and fetal hypoxia, which requires fetal cardiovascular adaptation. Both maternal and fetal Doppler alterations are present, allowing for risk stratification and monitoring. Although the precise etiology for FGR due to placental causes is unknown, placental thrombosis, infarcts and hypercoagulability are frequently seen, suggesting a role for the activation of the coagulation cascade in the genesis of FGR. Currently, the management of early FGR is limited to the monitoring of fetal Doppler parameters until the risks for preterm delivery outweight the benefits of ongoing monitoring. As such, there is a special need for effective preventive and therapeutic interventions that improve the outcomes. Low molecular weight heparin (LMWH), for its anticoagulant and anti-inflammatory properties has been suggested as a possible therapeutic agent in this setting. The investigators will randomize the participants to two intervention arms in a one-to-one ratio, using a computer generated randomization program. The randomization will be stratified for gestational age at diagnosis of FGR (22 to 26 weeks and \\>26 to 32 weeks). The experimental group will be administered enoxaparin subcutaneous injections (40 mg, 4000 IU daily) and the control group will be provided standard of care. Both groups will start intervention immediately after the diagnosis of FGR, and will continue it until 36 weeks of gestation or 12 hours before delivery, whichever comes first.'}, 'eligibilityModule': {'sex': 'FEMALE', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'genderBased': True, 'genderDescription': 'biologic (genotipic and fenotipic) female sex', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. being 18 years old or older\n2. being able to provide consent\n3. having a viable singleton pregnancy with diagnosed early FGR confirmed in our unit according to the 2020 International Society of Ultrasound in Obstetrics \\& Gynecology (ISUOG) criteria (one solitary parameter: estimated fetal weight/ abdominal circumference lower than the 3rd centile or absent end-diastolic flow in umbilical artery; or estimated fetal weight/abdominal circumference below the 10th centile combined with either umbilical artery pulsatility index \\> 95th centile or uterine artery mean pulsatility index \\> 95th centile)\n\nExclusion Criteria:\n\n1. multiple gestation;\n2. diagnosed fetal chromosomal abnormalities;\n3. associated fetal morphological malformations;\n4. evidence of fetal infection (serological or after invasive testing);\n5. use of LMWH or NFH in the index pregnancy before randomization or start of any of these medications for another indication if the patient is in the control group\n6. present use of systemic salicylates in anti-inflammatory dosage (\\> 150mg/day) or NSAIDs (including ketorolac)\n7. maternal history of allergy to LMWH or non-fractionated heparin (NFH);\n8. hypersensitivity to pork products;\n9. maternal history of heparin-induced thrombocytopenia;\n10. maternal thrombocytopenia (platelets \\< 100 000);\n11. history of maternal hemophilia or Von Willebrand disease\n12. presence of placental hematoma;\n13. maternal diabetic retinopathy;\n14. bacterial endocarditis;\n15. active clinically significant bleeding and conditions with a high risk of hemorrhage, including recent hemorrhagic stroke, gastrointestinal ulcer, presence of malignant neoplasm at high risk of bleeding, recent brain, spinal or ophthalmic surgery, known or suspected esophageal varices, arteriovenous malformations, vascular aneurysms or major intraspinal or intracerebral vascular abnormalities;\n16. persistent blood pressure \\> 160/100 mmHg, despite optimal anti-hypertensive regimen;\n17. history of severe renal disease (eGFR \\<30mL/min);\n18. known or suspected hepatic impairment;\n19. current participation in another clinical trial;\n20. patients that are not part of the national health system (SNS);\n21. delivery already scheduled, or predicted in the next 7 days.'}, 'identificationModule': {'nctId': 'NCT04762992', 'acronym': 'HepaGrowth', 'briefTitle': 'LMWH for Treatment of Early Fetal Growth Restriction (HepaGrowth)', 'organization': {'class': 'OTHER', 'fullName': 'Centro Hospitalar de Lisboa Central'}, 'officialTitle': 'Low Molecular Weight Heparin for the Treatment of Early Fetal Growth Restriction', 'orgStudyIdInfo': {'id': 'CHULC.CI.452.2018'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Intervention group, enoxaparin', 'description': 'Enoxaparin subcutaneous injections', 'interventionNames': ['Drug: subcutaneous Enoxaparin']}, {'type': 'OTHER', 'label': 'Standard of care', 'description': 'Obsteric standard of care', 'interventionNames': ['Other: standard of care']}], 'interventions': [{'name': 'subcutaneous Enoxaparin', 'type': 'DRUG', 'otherNames': ['experimental'], 'description': 'Enoxaparin subcutaneous injections (40 mg, 4000 IU daily) starting immediately after the diagnosis of FGR, and until 36 weeks of gestation or 12 hours before delivery, whichever comes first.', 'armGroupLabels': ['Intervention group, enoxaparin']}, {'name': 'standard of care', 'type': 'OTHER', 'description': 'Obsteric standard of care.', 'armGroupLabels': ['Standard of care']}]}, 'contactsLocationsModule': {'locations': [{'zip': '1050-170', 'city': 'Lisbon', 'country': 'Portugal', 'facility': 'Centro de Diagnóstico Pré-Natal, Maternidade Dr. Alfredo da Costa, Centro Hospitalar Universitário de Lisboa Central', 'geoPoint': {'lat': 38.72509, 'lon': -9.1498}}], 'overallOfficials': [{'name': 'Fátima Serrano, MD, PhD', 'role': 'STUDY_CHAIR', 'affiliation': 'Centro Hospitalar Universitário de Lisboa Central'}, {'name': 'Catarina Palma-dos-Reis, MD, MSc', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Centro Hospitalar Universitário de Lisboa Central'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Centro Hospitalar de Lisboa Central', 'class': 'OTHER'}, 'collaborators': [{'name': 'NOVA Medical School', 'class': 'OTHER'}], 'responsibleParty': {'type': 'SPONSOR'}}}}