Ignite Creation Date:
2025-12-24 @ 3:49 PM
Ignite Modification Date:
2025-12-27 @ 10:02 AM
Study NCT ID:
NCT05350592
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-07-17
First Post:
2022-03-08
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Low-Dose Dobutamine and Single-Dose Tocilizumab in Acute Myocardial Infarction With High Risk of Cardiogenic Shock
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D012770', 'term': 'Shock, Cardiogenic'}, {'id': 'D007249', 'term': 'Inflammation'}, {'id': 'D000072657', 'term': 'ST Elevation Myocardial Infarction'}], 'ancestors': [{'id': 'D009203', 'term': 'Myocardial Infarction'}, {'id': 'D017202', 'term': 'Myocardial Ischemia'}, {'id': 'D006331', 'term': 'Heart Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}, {'id': 'D014652', 'term': 'Vascular Diseases'}, {'id': 'D007238', 'term': 'Infarction'}, {'id': 'D007511', 'term': 'Ischemia'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D009336', 'term': 'Necrosis'}, {'id': 'D012769', 'term': 'Shock'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C502936', 'term': 'tocilizumab'}, {'id': 'D004280', 'term': 'Dobutamine'}, {'id': 'D012965', 'term': 'Sodium Chloride'}], 'ancestors': [{'id': 'D002395', 'term': 'Catecholamines'}, {'id': 'D000588', 'term': 'Amines'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D010627', 'term': 'Phenethylamines'}, {'id': 'D005021', 'term': 'Ethylamines'}, {'id': 'D002396', 'term': 'Catechols'}, {'id': 'D010636', 'term': 'Phenols'}, {'id': 'D001555', 'term': 'Benzene Derivatives'}, {'id': 'D006841', 'term': 'Hydrocarbons, Aromatic'}, {'id': 'D006844', 'term': 'Hydrocarbons, Cyclic'}, {'id': 'D006838', 'term': 'Hydrocarbons'}, {'id': 'D002712', 'term': 'Chlorides'}, {'id': 'D006851', 'term': 'Hydrochloric Acid'}, {'id': 'D017606', 'term': 'Chlorine Compounds'}, {'id': 'D007287', 'term': 'Inorganic Chemicals'}, {'id': 'D017670', 'term': 'Sodium Compounds'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2022-08-01', 'size': 563719, 'label': 'Study Protocol and Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'Prot_SAP_001.pdf', 'typeAbbrev': 'Prot_SAP', 'uploadDate': '2024-07-10T08:50', 'hasProtocol': True}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'FACTORIAL', 'interventionModelDescription': '2x2'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 100}}, 'statusModule': {'overallStatus': 'ACTIVE_NOT_RECRUITING', 'startDateStruct': {'date': '2022-03-13', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-07', 'completionDateStruct': {'date': '2025-09-30', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-07-16', 'studyFirstSubmitDate': '2022-03-08', 'studyFirstSubmitQcDate': '2022-04-21', 'lastUpdatePostDateStruct': {'date': '2025-07-17', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2022-04-28', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2025-06-30', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'ProBNP', 'timeFrame': '48 hours', 'description': 'ProBNP plasma concentration being assessed at multiple time points (including the primary endpoint) will be analyzed by application of a linear mixed model of covariance. As the biomarker will be measured prior to initiation of the study drug, the models will be baseline corrected (i.e., constrained linear mixed models, CLMM). The main result of these analyses will be the treatment-by-time interaction as a marker of whether the proBNP levels change differently over time in the treatment versus the placebo arm.'}], 'secondaryOutcomes': [{'measure': 'CS and/or cardiac arrest', 'timeFrame': 'Index admission', 'description': 'Number of patients developing in-hospital CS and/or in-hospital cardiac arrest'}, {'measure': 'Acute Infarct Size', 'timeFrame': 'Admission', 'description': 'Magnetic-resonance imaging-estimated infarct size'}, {'measure': 'Post-infarction Salvaged Myocardium', 'timeFrame': '3 months', 'description': 'Magnetic-resonance imaging-estimated infarct size'}, {'measure': 'Additional biomarkers', 'timeFrame': 'Index admission', 'description': 'Reflecting neurohormonal activation, endothelial function/damage, inflammation (pro- and anti-inflammatory processes - including IL-6 and C-reactive peptide (CRP)), connective tissue damage, organ dysfunction, and other relevant physiological processes'}, {'measure': 'Post-procedure assessment', 'timeFrame': 'Index admission', 'description': "Survey of PCI operator's post-procedure clinical assessment of the patient's survival at discharge (yes/no)"}, {'measure': 'Development of non-cardiac arrest arrythmia', 'timeFrame': 'Index admission', 'description': 'Number of patients and number of per-patient episodes of sustained ventricular tachycardia or atrial fibrillation with a frequency above 120 for more than 30 minutes'}, {'measure': '2D echocardiographic measurements of hemodynamics', 'timeFrame': 'Admisson, 3 months', 'description': 'VTI and left ventricular function including strain measurements according to protocol'}, {'measure': 'Re-admission', 'timeFrame': 'One year', 'description': 'Number of all cause and cardiovascular admissions during the first year after index hospitalization'}, {'measure': 'Heart Quality of Life (HeartQoL)', 'timeFrame': 'Admission, 3 months', 'description': 'Heart-specific Quality of Life Questionnaire'}, {'measure': 'EuroQol Group EQ-5D Quality of Life (EQ-5D-5L)', 'timeFrame': 'Admission, 3 months', 'description': 'Quality of Life Questionnaire'}, {'measure': 'HADS (Hospital Anxiety and Depression Scale)', 'timeFrame': 'Admission, 3 months', 'description': 'In-patient Anxiety and Depression Questionnaire'}, {'measure': 'The Montreal Cognitive Assessment (MOCA)', 'timeFrame': 'Admission, 3 months', 'description': 'Clinician-administered Cognitive Test'}, {'measure': 'Clinical Frailty Scale (CFS)', 'timeFrame': 'Admission, 3 months', 'description': 'Clinician-administered Assessment'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['acute myocardial infarction', 'cardiogenic shock', 'AMI', 'inflammation', 'proBNP', 'AMI-CS', 'infarct size', 'STEMI'], 'conditions': ['Acute Myocardial Infarction', 'Cardiogenic Shock']}, 'referencesModule': {'references': [{'pmid': '39478521', 'type': 'BACKGROUND', 'citation': 'Holle SLD, Kunkel JB, Hassager C, Pecini R, Wiberg S, Palm P, Holmvang L, Bang LE, Kjaergaard J, Thomsen JH, Engstrom T, Moller JE, Lonborg JT, Soholm H, Frydland M. Low-dose dobutamine in acute myocardial infarction with intermediate to high risk of cardiogenic shock development (the DOBERMANN-D trial): study protocol for a double-blinded, placebo-controlled, single-center, randomized clinical trial. Trials. 2024 Oct 30;25(1):731. doi: 10.1186/s13063-024-08567-y.'}, {'pmid': '39501388', 'type': 'BACKGROUND', 'citation': 'Kunkel JB, Holle SLD, Hassager C, Pecini R, Wiberg S, Palm P, Holmvang L, Bang LE, Kjaergaard J, Thomsen JH, Engstrom T, Moller JE, Lonborg JT, Frydland M, Soholm H. Interleukin-6 receptor antibodies (tocilizumab) in acute myocardial infarction with intermediate to high risk of cardiogenic shock development (DOBERMANN-T): study protocol for a double-blinded, placebo-controlled, single-center, randomized clinical trial. Trials. 2024 Nov 5;25(1):739. doi: 10.1186/s13063-024-08573-0.'}]}, 'descriptionModule': {'briefSummary': 'In the present study, we aim to investigate the effects of dobutamine infusion and/or a single intravenous (IV) dose of the IL-6 antagonist Tocilizumab administered after percutaneous coronary intervention (PCI) to patients with acute myocardial infarction (AMI) presenting \\< 24 hours from onset of chest pain and an intermediate to high risk of cardiogenic shock (CS) by assessment with the ORBI risk score (≥10 - not in overt shock at hospital admission).\n\nPlasma concentrations of pro-B-type natriuretic peptide (proBNP) as a proxy for development of cardiogenic shock (CS) and hemodynamic instability will be sampled for primary endpoint analysis.\n\nEffects on clinical parameters, mortality, morbidity as well as specific indicators of inflammation, cardiac function, and infarct size will secondarily be assessed noninvasively.\n\nThe rationale behind the current study is that inflammatory and neurohormonal responses are associated with subclinical hemodynamic instability in patients with AMI with high risk of CS have worse outcomes. The potentially unstable condition may be targeted pharmacologically as an add-on to existing therapy. This is investigated in patients at elevated risk of CS by sampling biomarkers reflecting the inflammatory and neurohormonal responses, as well as determining effects on patient outcomes and infarct size.', 'detailedDescription': 'The planned study is an investigator-initiated, randomized, double blinded clinical trial.\n\nConsecutive patients at Copenhagen University Hospital, Rigshospitalet admitted with AMI \\< 24 hours from chest pain will be screened.\n\nPatients eligible for trial inclusion will be randomized 2:2 to receive a continuous IV dobutamine infusion of 5 mcg/kg/minute versus placebo for 24 hours and to receive a single IV dose of tocilizumab (1-hour infusion) versus placebo administered after PCI.\n\nTreatment with the investigational drug will be initiated as soon as possible but no later than 2 hours after transfer to the coronary care unit (CCU) and after informed consent. All included patients will follow usual treatment according to current guidelines.\n\nThe biomarker proBNP will be measured in blood samples drawn upon hospital admission in patients with ORBI risk score ≥10, and after 12, 24, 36 and 48 hours from admission.\n\nAfter treatment termination, 2D-echocardiography will be performed acutely and within 2 days to evaluate left ventricular ejection fraction (LVEF), and cardiac magnetic resonance imaging (cMRi) with late gadolinium enhancement technique prior to hospital discharge as close to 48 hours post-MI and after 3 months after discharge will be performed to calculate area at risk and salvage index after AMI.Blood samples (40 mL) will be obtained and stored in a biobank for subsequent measurement of biomarkers reflecting inflammation, neurohormonal activation, neuronal injury, connective tissue function and other relevant pathophysiological processes.\n\nThese biomarkers will solely have research interest and no clinical implications. Furthermore, no genetic biomarkers and markers associated with malignancy development will be measured. Any leftover blood from the research biobank will be transferred to a biobank for future research and stored for up to 10 years solely for research purposes. After this period blood samples will be destroyed.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Acute myocardial infarction\n* Revascularization with PCI\n* Presentation within 24 hours of chest pain\n* ORBI risk score ≥ 10\n* Age ≥ 18\n\nExclusion Criteria:\n\n* Unwilling to give informed consent to study participation\n* Unable to give consent due to language barrier\n* Comatose after cardiac arrest\n* Cardiogenic shock with systolic blood pressure \\< 100 mmHg for more than 30 minutes or need for vasopressor to maintain blood pressure and arterial lactate \\> 2,5 (2,0) mmol/L developed before leaving the cath. lab.\n* Other major clinical non-coronary condition (stroke, sepsis etc.), which can explain a high ORBI risk score\n* Referral for acute coronary artery bypass grafting (CABG) (\\< 24 hours) after the CAG\n* Contraindications against dobutamine infusion (sustained ventricular tachycardia prior to admission or noted in the cath.lab., known pheochromocytoma, idiopathic hypertrophic subaortic stenosis)\n* Tocilizumab allergy\n* Pregnant- or breastfeeding women\n* Known liver disease/dysfunction\n* Ongoing uncontrollable infection\n* Immune deficiency/treatment with immunosuppressants\n* Known, uncontrolled gastrointestinal (GI) disease predisposing to GI perforation'}, 'identificationModule': {'nctId': 'NCT05350592', 'acronym': 'DOBERMANN', 'briefTitle': 'Low-Dose Dobutamine and Single-Dose Tocilizumab in Acute Myocardial Infarction With High Risk of Cardiogenic Shock', 'organization': {'class': 'OTHER', 'fullName': 'Rigshospitalet, Denmark'}, 'officialTitle': 'Low-dose Dobutamine Infusion and Single-dose Tocilizumab in Acute Myocardial Infarction Patients With High Risk of Cardiogenic Shock Development - a 2x2 Multifactorial, Double-blinded, Randomized, Placebo Controlled Trial', 'orgStudyIdInfo': {'id': 'RH-CARD-Pharma001'}, 'secondaryIdInfos': [{'id': '2021-002028-19', 'type': 'EUDRACT_NUMBER'}, {'id': 'H-21045751', 'type': 'REGISTRY', 'domain': 'National Committee on Health Research Ethics'}, {'id': 'U1111-1277-8523', 'type': 'REGISTRY', 'domain': 'WHO Universal Trial Number'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Tocilizumab + Dobutamine', 'description': 'Tocilizumab IV 280 mg (100mL/hour, 1 hour) Dobutamine IV 5 micrograms/kg/minute (5mL/hour, 24 hours)', 'interventionNames': ['Drug: Tocilizumab', 'Drug: Dobutamine']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Tocilizumab + Placebo', 'description': 'Tocilizumab IV 280 mg (100mL/hour, 1 hour) NaCl 0,9% IV (5mL/hour, 24 hours)', 'interventionNames': ['Drug: Tocilizumab', 'Drug: NaCl 0.9%']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Placebo + Dobutamine', 'description': 'NaCl 0,9% IV (100mL/hour, 1 hour) Dobutamine IV 5 micrograms/kg/minute (5mL/hour, 24 hours)', 'interventionNames': ['Drug: Dobutamine', 'Drug: NaCl 0.9%']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo + Placebo', 'description': 'NaCl 0,9% IV (100mL/hour, 1 hour) NaCl 0,9% IV (5mL/hour, 24 hours)', 'interventionNames': ['Drug: NaCl 0.9%']}], 'interventions': [{'name': 'Tocilizumab', 'type': 'DRUG', 'otherNames': ['RoActemra (Actemra)'], 'description': 'Single bolus', 'armGroupLabels': ['Tocilizumab + Dobutamine', 'Tocilizumab + Placebo']}, {'name': 'Dobutamine', 'type': 'DRUG', 'otherNames': ['Dobutrex'], 'description': 'Continous weight-adjusted infusion', 'armGroupLabels': ['Placebo + Dobutamine', 'Tocilizumab + Dobutamine']}, {'name': 'NaCl 0.9%', 'type': 'DRUG', 'otherNames': ['Saline isotonic'], 'description': 'Placebo comparator and diluent', 'armGroupLabels': ['Placebo + Dobutamine', 'Placebo + Placebo', 'Tocilizumab + Placebo']}]}, 'contactsLocationsModule': {'locations': [{'zip': '2100', 'city': 'Copenhagen', 'country': 'Denmark', 'facility': 'Rigshospitalet, Copenhagen University Hospital', 'geoPoint': {'lat': 55.67594, 'lon': 12.56553}}], 'overallOfficials': [{'name': 'Helle Søholm, MD, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Dept. of Cardiology, Rigshospitalet'}, {'name': 'Martin Frydland, MD, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Dept. of Cardiology, Rigshospitalet'}]}, 'ipdSharingStatementModule': {'infoTypes': ['STUDY_PROTOCOL', 'SAP', 'ICF', 'CSR'], 'timeFrame': 'Access and final IPD criteria is pending final, complete publication of the study.', 'ipdSharing': 'YES', 'description': 'Data is planned to be available upon reasonable request via the Principal Investigator pending final, complete publication of the study.', 'accessCriteria': 'Access to trial IPD can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA)'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Rigshospitalet, Denmark', 'class': 'OTHER'}, 'collaborators': [{'name': 'Novo Nordisk A/S', 'class': 'INDUSTRY'}, {'name': 'Simon Spies Fonden', 'class': 'UNKNOWN'}, {'name': 'Helge Peetz og Verner Peetz og hustru Vilma Peetz Legat', 'class': 'UNKNOWN'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'MD, PhD', 'investigatorFullName': 'Helle Søholm, MD, PhD', 'investigatorAffiliation': 'Rigshospitalet, Denmark'}}}}