Ignite Creation Date:
2025-12-25 @ 4:29 AM
Ignite Modification Date:
2026-01-04 @ 8:55 AM
Study NCT ID:
NCT03247920
Status:
COMPLETED
Last Update Posted:
2021-08-24
First Post:
2017-07-03
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Reduction of Intravenous Antibiotics In Neonates
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D000071074', 'term': 'Neonatal Sepsis'}], 'ancestors': [{'id': 'D018805', 'term': 'Sepsis'}, {'id': 'D007239', 'term': 'Infections'}, {'id': 'D007232', 'term': 'Infant, Newborn, Diseases'}, {'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}, {'id': 'D018746', 'term': 'Systemic Inflammatory Response Syndrome'}, {'id': 'D007249', 'term': 'Inflammation'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D019980', 'term': 'Amoxicillin-Potassium Clavulanate Combination'}, {'id': 'D000900', 'term': 'Anti-Bacterial Agents'}], 'ancestors': [{'id': 'D019818', 'term': 'Clavulanic Acid'}, {'id': 'D002969', 'term': 'Clavulanic Acids'}, {'id': 'D047090', 'term': 'beta-Lactams'}, {'id': 'D007769', 'term': 'Lactams'}, {'id': 'D000577', 'term': 'Amides'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D000658', 'term': 'Amoxicillin'}, {'id': 'D000667', 'term': 'Ampicillin'}, {'id': 'D010400', 'term': 'Penicillin G'}, {'id': 'D010406', 'term': 'Penicillins'}, {'id': 'D013457', 'term': 'Sulfur Compounds'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D004338', 'term': 'Drug Combinations'}, {'id': 'D004364', 'term': 'Pharmaceutical Preparations'}, {'id': 'D000890', 'term': 'Anti-Infective Agents'}, {'id': 'D045506', 'term': 'Therapeutic Uses'}, {'id': 'D020228', 'term': 'Pharmacologic Actions'}, {'id': 'D020164', 'term': 'Chemical Actions and Uses'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'SINGLE', 'whoMasked': ['OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Multicenter prospective randomized controlled non-inferiority trial'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 510}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2017-11-04', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2021-08', 'completionDateStruct': {'date': '2021-07-15', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2021-08-23', 'studyFirstSubmitDate': '2017-07-03', 'studyFirstSubmitQcDate': '2017-08-09', 'lastUpdatePostDateStruct': {'date': '2021-08-24', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2017-08-14', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2021-06-15', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Bacterial re-infection within 28 days after cessation of antibiotic treatment (within 35 days after initial presentation)', 'timeFrame': '0-35 days'}], 'secondaryOutcomes': [{'measure': 'Duration of hospitalization', 'timeFrame': '0-35 days after birth'}, {'measure': 'Percentage of re-admission', 'timeFrame': '0-35 days after birth'}, {'measure': 'Total costs and cost-effectiveness', 'timeFrame': '0-35 days after birth', 'description': 'Cost-effectiveness of intravenous to oral switch compared to a full course of antibiotics + possible extra costs due to early antibiotic switch'}, {'measure': 'Difference in Quality of Life between oral and intravenous antibiotic treatment', 'timeFrame': '0-35 days after birth', 'description': 'Two questionnaires on day 7 and 21 after admission, filled in by both parents. Data will be provided in a descriptive manner as no validated QoL questionnaires exist for neonates.'}, {'measure': 'Time above MIC (T>MIC) of oral amoxicillin.', 'timeFrame': '0-7 days', 'description': '2 blood samples after administration of antibiotic suspension at different time points will be taken.\n\nTime above MIC (T\\>MIC) will be defined. Target MIC is 8 mg/liter.'}, {'measure': 'Time above MIC (T>MIC) of oral clavulanic acid.', 'timeFrame': '0-7 days', 'description': '2 blood samples after administration of antibiotic suspension at different time points will be taken.\n\nTime above MIC (T\\>MIC) will be defined. Target MIC is 8 mg/liter.'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Antibiotic switch therapy', 'Amoxicillin/clavulanic acid'], 'conditions': ['Neonatal Infection', 'Neonatal SEPSIS']}, 'referencesModule': {'references': [{'pmid': '36088952', 'type': 'DERIVED', 'citation': 'Keij FM, Kornelisse RF, Hartwig NG, van der Sluijs-Bens J, van Beek RHT, van Driel A, van Rooij LGM, van Dalen-Vink I, Driessen GJA, Kenter S, von Lindern JS, Eijkemans M, Stam-Stigter GM, Qi H, van den Berg MM, Baartmans MGA, van der Meer-Kappelle LH, Meijssen CB, Norbruis OF, Heidema J, van Rossem MC, den Butter PCP, Allegaert K, Reiss IKM, Tramper-Stranders GA. Efficacy and safety of switching from intravenous to oral antibiotics (amoxicillin-clavulanic acid) versus a full course of intravenous antibiotics in neonates with probable bacterial infection (RAIN): a multicentre, randomised, open-label, non-inferiority trial. Lancet Child Adolesc Health. 2022 Nov;6(11):799-809. doi: 10.1016/S2352-4642(22)00245-0. Epub 2022 Sep 9.'}, {'pmid': '31289068', 'type': 'DERIVED', 'citation': 'Keij FM, Kornelisse RF, Hartwig NG, Mauff K, Poley MJ, Allegaert K, Reiss IKM, Tramper-Stranders GA. RAIN study: a protocol for a randomised controlled trial evaluating efficacy, safety and cost-effectiveness of intravenous-to-oral antibiotic switch therapy in neonates with a probable bacterial infection. BMJ Open. 2019 Jul 9;9(7):e026688. doi: 10.1136/bmjopen-2018-026688.'}]}, 'descriptionModule': {'briefSummary': 'Randomized controlled open-label non-inferiority trial comparing complete intravenous antibiotic treatment with a short iv. course followed by oral antibiotics in neonates (0-28 days) with probable bacterial infection.\n\nPrimary outcome:\n\n\\- Bacterial re-infection within 28 days after finishing of antibacterial therapy.\n\nSecondary outcome(s):\n\n* Pharmacokinetic profile of oral amoxicillin/clavulanic acid\n* Quality of life\n* Cost-effectiveness\n* Alterations in gut microbiome\n* Use of molecular techniques for better detection of bacterial pathogens', 'detailedDescription': 'Neonates have a high antibiotic consumption because of their susceptibility for bacterial infections. Since the early diagnosis of bacterial infection in neonates is difficult, intravenous broad-spectrum antimicrobial therapy is usually started promptly after subtle symptoms. The majority of neonates become asymptomatic shortly after initiation; when infection is probable or proven by elevated inflammatory markers and/or a positive blood culture, intravenous antibiotics are administered for at least 7 days.\n\nHowever, for neonates blood culture has a limited sensitivity. Therefore, the majority of neonates with probable infection are treated for a prolonged time with intravenous broad-spectrum antimicrobial therapy. In older children, intravenous antibiotics are often changed to oral antibiotics after cessation of symptoms and decreasing inflammatory parameters. This is not yet widely practised in neonates because of uncertainties in pharmacokinetics. Two explorative small studies from France and Italy into neonatal antibiotic switch therapy suggest that follow-up treatment with an oral antibiotic is promising; but the non-inferiority and safety was not yet properly addressed. Neonatal switch therapy, if proven to be safe and efficacious, would have a major impact on neonatal well-being, mother-to-child bonding and moreover costs.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD'], 'maximumAge': '28 Days', 'minimumAge': '1 Day', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Neonates (≥ 35+0 weeks, 0-28 days old, ≥ 2 kg)\n* Probable bacterial infection defined as clinical symptoms and/or maternal risk factors and elevated inflammatory markers for which empiric broad-spectrum antibiotic treatment was initiated and needs to be continued for \\> 48 hours\n* Clinically well\n* Toleration of oral feeding without overt vomiting\n* Signed informed consent\n\nExclusion Criteria:\n\n* Proven bloodstream infection\n* Absence of blood culture\n* Severe localized infection (meningitis, osteomyelitis, necrotizing enterocolitis)\n* Severe clinical sepsis (compromised circulation, need for mechanical ventilation)\n* Continuous need for a central venous line\n* Severe hyperbilirubinemia exceeding the exchange level\n* Parents inability to administer medication\n* Major congenital or syndromic anomalies'}, 'identificationModule': {'nctId': 'NCT03247920', 'acronym': 'RAIN', 'briefTitle': 'Reduction of Intravenous Antibiotics In Neonates', 'organization': {'class': 'OTHER', 'fullName': 'Franciscus Gasthuis'}, 'officialTitle': 'Intravenous to Oral Antibiotic Switch Therapy for Probable Neonatal Bacterial Infections: Clinical Efficacy, Safety and Cost-effectiveness', 'orgStudyIdInfo': {'id': 'RAIN'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Oral group', 'description': 'After 48 hours of intravenous antibiotics eligible neonates will switch to amoxicillin/clavulanic acid suspension for the remaining 5 days. When the oral suspension is well tolerated neonates can be discharged from hospital.\n\nIn order to investigate the pharmacokinetic profile of oral amoxicillin/clavulanic acid serum levels will be measured.', 'interventionNames': ['Drug: Amoxicillin Clavulanate']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Intravenous group', 'description': 'Neonates will complete the full course of antibiotics of 7 days intravenously in hospital following local protocol.', 'interventionNames': ['Drug: Antibiotics']}], 'interventions': [{'name': 'Amoxicillin Clavulanate', 'type': 'DRUG', 'description': 'Dose 75 mg/kg/day, (3dd 25 mg/kg). Concentration amoxicillin/clavulanic acid: 4:1', 'armGroupLabels': ['Oral group']}, {'name': 'Antibiotics', 'type': 'DRUG', 'description': 'Intravenous antibiotic therapy following local protocol', 'armGroupLabels': ['Intravenous group']}]}, 'contactsLocationsModule': {'locations': [{'city': 'Amersfoort', 'country': 'Netherlands', 'facility': 'Meander Medical Center', 'geoPoint': {'lat': 52.155, 'lon': 5.3875}}, {'city': 'Arnhem', 'country': 'Netherlands', 'facility': 'Rijnstate Hospital', 'geoPoint': {'lat': 51.98, 'lon': 5.91111}}, {'city': 'Breda', 'country': 'Netherlands', 'facility': 'Amphia Hospital', 'geoPoint': {'lat': 51.58656, 'lon': 4.77596}}, {'city': 'Capelle aan den IJssel', 'country': 'Netherlands', 'facility': 'IJsselland Ziekenhuis', 'geoPoint': {'lat': 51.92917, 'lon': 4.57778}}, {'city': 'Delft', 'country': 'Netherlands', 'facility': 'Reinier de Graaf Gasthuis', 'geoPoint': {'lat': 52.00667, 'lon': 4.35556}}, {'city': 'Eindhoven', 'country': 'Netherlands', 'facility': 'Catharina Hospital', 'geoPoint': {'lat': 51.44083, 'lon': 5.47778}}, {'city': 'Enschede', 'country': 'Netherlands', 'facility': 'Medisch Spectrum Twente', 'geoPoint': {'lat': 52.21833, 'lon': 6.89583}}, {'city': 'Gouda', 'country': 'Netherlands', 'facility': 'Groene Hart Ziekenhuis', 'geoPoint': {'lat': 52.01667, 'lon': 4.70833}}, {'city': 'Nieuwegein', 'country': 'Netherlands', 'facility': 'Sint Antonius Ziekenhuis', 'geoPoint': {'lat': 52.02917, 'lon': 5.08056}}, {'city': 'Rotterdam', 'country': 'Netherlands', 'facility': "Erasmus MC-Sophia Children's Hospital", 'geoPoint': {'lat': 51.9225, 'lon': 4.47917}}, {'city': 'Rotterdam', 'country': 'Netherlands', 'facility': 'Franciscus Gasthuis', 'geoPoint': {'lat': 51.9225, 'lon': 4.47917}}, {'city': 'Rotterdam', 'country': 'Netherlands', 'facility': 'Ikazia Ziekenhuis', 'geoPoint': {'lat': 51.9225, 'lon': 4.47917}}, {'city': 'Rotterdam', 'country': 'Netherlands', 'facility': 'Maasstad Hospital', 'geoPoint': {'lat': 51.9225, 'lon': 4.47917}}, {'city': 'Schiedam', 'country': 'Netherlands', 'facility': 'Franciscus Vlietland', 'geoPoint': {'lat': 51.91917, 'lon': 4.38889}}, {'city': 'The Hague', 'country': 'Netherlands', 'facility': 'Haaglanden Medical Center', 'geoPoint': {'lat': 52.07667, 'lon': 4.29861}}, {'city': 'The Hague', 'country': 'Netherlands', 'facility': 'Juliana Kinderziekenhuis-Haga Hospital', 'geoPoint': {'lat': 52.07667, 'lon': 4.29861}}, {'city': 'Veldhoven', 'country': 'Netherlands', 'facility': 'Maxima Medisch Centrum', 'geoPoint': {'lat': 51.41833, 'lon': 5.40278}}, {'city': 'Zwolle', 'country': 'Netherlands', 'facility': 'Isala', 'geoPoint': {'lat': 52.5125, 'lon': 6.09444}}], 'overallOfficials': [{'name': 'Gerdien Tramper', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Franciscus Gasthuis & Vlietland'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'YES', 'description': 'Data will be made available on request through a repository and shared after consent of the principal investigator.'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Franciscus Gasthuis', 'class': 'OTHER'}, 'collaborators': [{'name': 'Erasmus Medical Center', 'class': 'OTHER'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Principal investigator, MD, PhD', 'investigatorFullName': 'Gerdien Tramper', 'investigatorAffiliation': 'Franciscus Gasthuis'}}}}