Ignite Creation Date:
2025-12-25 @ 2:37 AM
Ignite Modification Date:
2026-01-24 @ 3:59 AM
Study NCT ID:
NCT00866034
Status:
TERMINATED
Last Update Posted:
2014-03-19
First Post:
2009-03-19
Is Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Cetrotide Treatment Optimization
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'interventionBrowseModule': {'meshes': [{'id': 'C062876', 'term': 'cetrorelix'}, {'id': 'D010062', 'term': 'Ovulation Induction'}, {'id': 'C571801', 'term': 'follitropin alfa'}], 'ancestors': [{'id': 'D027724', 'term': 'Reproductive Techniques, Assisted'}, {'id': 'D012099', 'term': 'Reproductive Techniques'}, {'id': 'D013812', 'term': 'Therapeutics'}, {'id': 'D008919', 'term': 'Investigative Techniques'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'O.Hamdine@umcutrecht.nl', 'phone': '+31-88-7557524', 'title': 'Ouijdane Hamdine, MD', 'organization': 'UMC Utrecht'}, 'certainAgreement': {'piSponsorEmployee': True, 'restrictiveAgreement': False}, 'limitationsAndCaveats': {'description': 'The study was terminated prematurely because no significant difference was observed in clinical outcome after 617 inclusions. A much larger population would be needed to detect a small significant difference in favour of either study arm.'}}, 'adverseEventsModule': {'eventGroups': [{'id': 'EG000', 'title': 'Early Start CD2', 'description': 'Early fixed start of a daily dose of 0.25mg Cetrotide on cycle day 2, together with the initiation of daily treatment with exogenous gonadotropins.', 'otherNumAtRisk': 308, 'otherNumAffected': 20, 'seriousNumAtRisk': 308, 'seriousNumAffected': 4}, {'id': 'EG001', 'title': 'Late Start CD6', 'description': 'Late fixed start of a daily dose of 0.25mg Cetrotide on cycle day 6. As in the other arm of the study, exogenous gonadotropins will commence on cycle day 2.', 'otherNumAtRisk': 309, 'otherNumAffected': 18, 'seriousNumAtRisk': 309, 'seriousNumAffected': 8}], 'otherEvents': [{'term': 'cancellation due to hyperresponse', 'stats': [{'groupId': 'EG000', 'numAtRisk': 308, 'numEvents': 7, 'numAffected': 7}, {'groupId': 'EG001', 'numAtRisk': 309, 'numEvents': 3, 'numAffected': 3}], 'organSystem': 'Reproductive system and breast disorders'}, {'term': 'cancellation due to hyporesponse', 'stats': [{'groupId': 'EG000', 'numAtRisk': 308, 'numEvents': 13, 'numAffected': 13}, {'groupId': 'EG001', 'numAtRisk': 309, 'numEvents': 15, 'numAffected': 15}], 'organSystem': 'Reproductive system and breast disorders'}], 'seriousEvents': [{'term': 'OHSS', 'stats': [{'groupId': 'EG000', 'numAtRisk': 308, 'numEvents': 4, 'numAffected': 4}, {'groupId': 'EG001', 'numAtRisk': 309, 'numEvents': 8, 'numAffected': 8}], 'organSystem': 'Reproductive system and breast disorders'}], 'frequencyThreshold': '1.6'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Live Birth Rate Per Started Cycle and Live Birth From Cryopreserved Embryos Originating From, and Occurring Within 6 Months of the Initial Treatment Cycle Will be Included in the Total Live Birth Rate Per Started Cycle.', 'denoms': [{'units': 'Participants', 'counts': [{'value': '308', 'groupId': 'OG000'}, {'value': '309', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Early Start CD2', 'description': 'Early fixed start of a daily dose of 0.25mg Cetrotide on cycle day 2, together with the initiation of daily treatment with exogenous gonadotropins.'}, {'id': 'OG001', 'title': 'Late Start CD6', 'description': 'Late fixed start of a daily dose of 0.25mg Cetrotide on cycle day 6. As in the other arm of the study, exogenous gonadotropins will commence on cycle day 2.'}], 'classes': [{'categories': [{'measurements': [{'value': '26.7', 'groupId': 'OG000'}, {'value': '29.9', 'groupId': 'OG001'}]}]}], 'paramType': 'NUMBER', 'timeFrame': '2 years', 'unitOfMeasure': 'Cumulative live birth rate (%)', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Cumulative Ongoing Pregnancy Rate', 'denoms': [{'units': 'Participants', 'counts': [{'value': '308', 'groupId': 'OG000'}, {'value': '309', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Early Start CD2', 'description': 'Early fixed start of a daily dose of 0.25mg Cetrotide on cycle day 2, together with the initiation of daily treatment with exogenous gonadotropins.'}, {'id': 'OG001', 'title': 'Late Start CD6', 'description': 'Late fixed start of a daily dose of 0.25mg Cetrotide on cycle day 6. As in the other arm of the study, exogenous gonadotropins will commence on cycle day 2.'}], 'classes': [{'categories': [{'measurements': [{'value': '27.6', 'groupId': 'OG000'}, {'value': '31.4', 'groupId': 'OG001'}]}]}], 'paramType': 'NUMBER', 'timeFrame': '2 years', 'unitOfMeasure': 'cumulative ongoing pregnancy rate (%)', 'reportingStatus': 'POSTED'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'Endocrine Profile in the Early, Mid and Late Follicular Phase.', 'timeFrame': '2 years', 'description': '1. difference in endocrine profile between the 2 arms during the mid and late follicular phase\n2. influence of early elevated follicular phase progesterone levels on clinical outcome', 'reportingStatus': 'NOT_POSTED'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Early Start CD2', 'description': 'Early fixed start of a daily dose of 0.25mg Cetrotide on cycle day 2, together with the initiation of daily treatment with exogenous gonadotropins.'}, {'id': 'FG001', 'title': 'Late Start CD6', 'description': 'Late fixed start of a daily dose of 0.25mg Cetrotide on cycle day 6. As in the other arm of the study, exogenous gonadotropins will commence on cycle day 2.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '308'}, {'groupId': 'FG001', 'numSubjects': '309'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '292'}, {'groupId': 'FG001', 'numSubjects': '301'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '16'}, {'groupId': 'FG001', 'numSubjects': '8'}]}]}], 'recruitmentDetails': 'Recruitment period: September 2009 - July 2011 Six hundred and seventeen women undergoing IVF or ICSI were recruited from the IVF outpatient clinics of 13 fertility centres.', 'preAssignmentDetails': 'None were excluded before assignment.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '308', 'groupId': 'BG000'}, {'value': '309', 'groupId': 'BG001'}, {'value': '617', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Early Start CD2', 'description': 'Early fixed start of a daily dose of 0.25mg Cetrotide on cycle day 2, together with the initiation of daily treatment with exogenous gonadotropins.'}, {'id': 'BG001', 'title': 'Late Start CD6', 'description': 'Late fixed start of a daily dose of 0.25mg Cetrotide on cycle day 6. As in the other arm of the study, exogenous gonadotropins will commence on cycle day 2.'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Categorical', 'classes': [{'categories': [{'title': '<=18 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Between 18 and 65 years', 'measurements': [{'value': '308', 'groupId': 'BG000'}, {'value': '309', 'groupId': 'BG001'}, {'value': '617', 'groupId': 'BG002'}]}, {'title': '>=65 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '32.1', 'spread': '3.9', 'groupId': 'BG000'}, {'value': '32.2', 'spread': '4.2', 'groupId': 'BG001'}, {'value': '32.2', 'spread': '4.0', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '308', 'groupId': 'BG000'}, {'value': '309', 'groupId': 'BG001'}, {'value': '617', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'Netherlands', 'categories': [{'measurements': [{'value': '308', 'groupId': 'BG000'}, {'value': '309', 'groupId': 'BG001'}, {'value': '617', 'groupId': 'BG002'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 617}}, 'statusModule': {'whyStopped': 'Due to limited rate of patient inclusion', 'overallStatus': 'TERMINATED', 'startDateStruct': {'date': '2009-02'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2014-02', 'completionDateStruct': {'date': '2012-10', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2014-02-04', 'studyFirstSubmitDate': '2009-03-19', 'resultsFirstSubmitDate': '2013-10-17', 'studyFirstSubmitQcDate': '2009-03-19', 'lastUpdatePostDateStruct': {'date': '2014-03-19', 'type': 'ESTIMATED'}, 'resultsFirstSubmitQcDate': '2013-10-17', 'studyFirstPostDateStruct': {'date': '2009-03-20', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2013-12-17', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2012-10', 'type': 'ACTUAL'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Endocrine Profile in the Early, Mid and Late Follicular Phase.', 'timeFrame': '2 years', 'description': '1. difference in endocrine profile between the 2 arms during the mid and late follicular phase\n2. influence of early elevated follicular phase progesterone levels on clinical outcome'}], 'primaryOutcomes': [{'measure': 'Live Birth Rate Per Started Cycle and Live Birth From Cryopreserved Embryos Originating From, and Occurring Within 6 Months of the Initial Treatment Cycle Will be Included in the Total Live Birth Rate Per Started Cycle.', 'timeFrame': '2 years'}], 'secondaryOutcomes': [{'measure': 'Cumulative Ongoing Pregnancy Rate', 'timeFrame': '2 years'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['Cetrotide', 'IVF', 'ICSI', 'Treatment protocol'], 'conditions': ['In Vitro Fertilization', 'Intracytoplasmic Sperm Injection']}, 'referencesModule': {'references': [{'pmid': '24929258', 'type': 'DERIVED', 'citation': 'Hamdine O, Macklon NS, Eijkemans MJ, Laven JS, Cohlen BJ, Verhoeff A, van Dop PA, Bernardus RE, Lambalk CB, Oosterhuis GJ, Holleboom CA, van den Dool-Maasland GC, Verburg HJ, van der Heijden PF, Blankhart A, Fauser BC, Broekmans FJ; CETRO trial study group. Elevated early follicular progesterone levels and in vitro fertilization outcomes: a prospective intervention study and meta-analysis. Fertil Steril. 2014 Aug;102(2):448-454.e1. doi: 10.1016/j.fertnstert.2014.05.002. Epub 2014 Jun 11.'}, {'pmid': '24129613', 'type': 'DERIVED', 'citation': 'Hamdine O, Macklon NS, Eijkemans MJ, Laven JS, Cohlen BJ, Verhoeff A, van Dop PA, Bernardus RE, Lambalk CB, Oosterhuis GJ, Holleboom CA, van den Dool-Maasland GC, Verburg HJ, van der Heijden PF, Blankhart A, Fauser BC, Broekmans FJ; CETRO trial study group. Comparison of early versus late initiation of GnRH antagonist co-treatment for controlled ovarian stimulation in IVF: a randomized controlled trial. Hum Reprod. 2013 Dec;28(12):3227-35. doi: 10.1093/humrep/det374. Epub 2013 Oct 15.'}, {'pmid': '23809501', 'type': 'DERIVED', 'citation': 'Hamdine O, Broekmans FJ, Eijkemans MJ, Lambalk CB, Fauser BC, Laven JS, Macklon NS; CETRO trial study group. Early initiation of gonadotropin-releasing hormone antagonist treatment results in a more stable endocrine milieu during the mid- and late-follicular phases: a randomized controlled trial comparing gonadotropin-releasing hormone antagonist initiation on cycle day 2 or 6. Fertil Steril. 2013 Sep;100(3):867-74. doi: 10.1016/j.fertnstert.2013.05.031. Epub 2013 Jun 27.'}]}, 'descriptionModule': {'briefSummary': "Rationale:\n\nIn daily practice fertility treatment is increasingly patient focused and innovative medication and standardized treatment guidelines are being developed to improve patient convenience.\n\nGnRH antagonist cotreatment to prevent premature luteinization during ovarian stimulation for IVF and ICSI greatly reduces the burden of treatment, partly by reducing the number of injections by around 21 compared with the optimal GnRH agonist 'long' protocol. However, the optimal GnRH antagonist protocol is still not known. There are a number of reasons to suggest that both the simplicity of treatment and clinical outcomes could be further improved by commencing GnRH antagonist treatment on the same day on which ovarian stimulation is started. These include more synchronized follicle development and reduced rates of premature luteinization. This study will investigate whether a novel early fixed start protocol improves outcomes in comparison to the widely employed late fixed start protocol.\n\nObjective:\n\nTo demonstrate whether an early fixed start antagonist protocol improves the live birth rate compared with a late fixed start antagonist protocol by 5%.\n\nStudy design:\n\nProspective, multicenter, investigator sponsored, randomized controlled trial\n\nStudy population:\n\n* Normo-ovulatory women \\< 39 years with an indication for IVF or ICSI\n* No more than 2 previous unsuccessful IVF/ICSI cycles\n* BMI ≤ 32 kg/m2\n\nIntervention:\n\nTwo different GnRH antagonist treatment protocols used in daily practice will be compared. Patients will be randomized to receive one of the following two treatments:\n\n* Early fixed start: start GnRH antagonist treatment with Cetrotide 0.25 mg on the same day as FSH, cycle day 2.\n* Late fixed start: FSH will be administered from cycle day 2. GnRH antagonist treatment with Cetrotide 0.25 mg will commence on cycle day 6.\n\nMain study parameters/endpoints:\n\nThe primary endpoint is the live birth rate per started cycle. A secondary endpoint is the number of embryos available for transfer.\n\nNature and extent of the burden and risks associated with participation, benefit and group relatedness:\n\nIn addition to recording clinical outcomes, endocrine studies will be carried out at the UMC Utrecht in a sample of 200 participants who will be subjected to blood sampling at three points during the treatment cycle: prior to commencing treatment on cycle day 2, cycle day 6 and the day of hCG administration.The aim of this substudy was therefore to prospectively compare the effect of a cycle day 2 versus cycle day 6 fixed start GnRH antagonist protocol on LH, estradiol and progesterone levels in the mid and late follicular phase. In order to investigate whether the early fixed protocol exerts a significant extra burden on patients compared to the late start protocol, another group of 200 participants at the UMCU will be requested to complete the HADS questionnaire (Hospital Anxiety and Depression Scale)."}, 'eligibilityModule': {'sex': 'FEMALE', 'stdAges': ['ADULT'], 'maximumAge': '39 Years', 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Normo-ovulatory women \\< 39 years with an indication for IVF or ICSI\n\nExclusion Criteria:\n\n* More than 2 previous unsuccessful IVF/ICSI cycles\n* BMI \\> 32 kg/m2'}, 'identificationModule': {'nctId': 'NCT00866034', 'briefTitle': 'Cetrotide Treatment Optimization', 'organization': {'class': 'OTHER', 'fullName': 'UMC Utrecht'}, 'officialTitle': 'Prospective, Multicenter,Randomized Controlled Trial Towards Identifying the Optimal GnRH Antagonist Treatment Protocol', 'orgStudyIdInfo': {'id': 'CETRO Trial'}, 'secondaryIdInfos': [{'id': 'CCMO: NL23973.041.08'}, {'id': 'METC: 08-262/G-K'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'CD2', 'description': 'Early fixed start of a daily dose of 0.25mg Cetrotide on cycle day 2, together with the initiation of daily treatment with exogenous gonadotropins.', 'interventionNames': ['Drug: Cetrotide (Ovarian stimulation)']}, {'type': 'EXPERIMENTAL', 'label': 'CD6', 'description': 'Late fixed start of a daily dose of 0.25mg Cetrotide on cycle day 6. As in the other arm of the study, exogenous gonadotropins will commence on cycle day 2.', 'interventionNames': ['Drug: Cetrotide (Ovarian stimulation)']}], 'interventions': [{'name': 'Cetrotide (Ovarian stimulation)', 'type': 'DRUG', 'otherNames': ['Gonal-F', 'Cetrorelix'], 'description': 'Fixed start of a daily dose of 0.25mg Cetrotide on cycle day 2', 'armGroupLabels': ['CD2']}, {'name': 'Cetrotide (Ovarian stimulation)', 'type': 'DRUG', 'otherNames': ['Gonal-F', 'Cetrorelix'], 'description': 'Late fixed start of a daily dose of 0.25mg Cetrotide on cycle day 6.', 'armGroupLabels': ['CD6']}]}, 'contactsLocationsModule': {'locations': [{'city': 'Utrecht', 'state': 'Utrecht', 'country': 'Netherlands', 'facility': 'University Medical Center Utrecht', 'geoPoint': {'lat': 52.09083, 'lon': 5.12222}}], 'overallOfficials': [{'name': 'Nick S Macklon, Prof, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'UMC Utrecht'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Bart CJM Fauser', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR_INVESTIGATOR', 'investigatorTitle': 'Professor of Reproductive Medicine and Gynecology', 'investigatorFullName': 'Bart CJM Fauser', 'investigatorAffiliation': 'UMC Utrecht'}}}}