Ignite Creation Date:
2025-12-25 @ 3:30 AM
Ignite Modification Date:
2026-02-25 @ 11:47 PM
Study NCT ID:
NCT03387605
Status:
UNKNOWN
Last Update Posted:
2019-05-23
First Post:
2017-12-15
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Effect of Ivabradine in Stage D HF/Cardiogenic Shock Patients on Dobutamine
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D006333', 'term': 'Heart Failure'}, {'id': 'D012770', 'term': 'Shock, Cardiogenic'}, {'id': 'D013610', 'term': 'Tachycardia'}], 'ancestors': [{'id': 'D006331', 'term': 'Heart Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}, {'id': 'D009203', 'term': 'Myocardial Infarction'}, {'id': 'D017202', 'term': 'Myocardial Ischemia'}, {'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'}, {'id': 'D001145', 'term': 'Arrhythmias, Cardiac'}, {'id': 'D000075224', 'term': 'Cardiac Conduction System Disease'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000077550', 'term': 'Ivabradine'}], 'ancestors': [{'id': 'D001552', 'term': 'Benzazepines'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Randomized, Double Blind, Placebo Controlled single center study.'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 40}}, 'statusModule': {'overallStatus': 'UNKNOWN', 'lastKnownStatus': 'RECRUITING', 'startDateStruct': {'date': '2018-03-15', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2019-05', 'completionDateStruct': {'date': '2020-06', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2019-05-21', 'studyFirstSubmitDate': '2017-12-15', 'studyFirstSubmitQcDate': '2017-12-22', 'lastUpdatePostDateStruct': {'date': '2019-05-23', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2018-01-02', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2020-01', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Heart rate', 'timeFrame': '72 hours', 'description': 'Heart rate will be measured and any changes noted'}], 'secondaryOutcomes': [{'measure': 'cardiac index', 'timeFrame': '72 hours', 'description': 'cardiac index will be assessed by pulmonary artery catheter and any changes noted'}, {'measure': 'plasma brain natriuretic peptide (BNP) level', 'timeFrame': '72 hours', 'description': 'Labs will be drawn for plasma BNP blood test and any changes noted'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': False, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Heart Failure', 'Cardiogenic Shock', 'Tachycardia']}, 'referencesModule': {'references': [{'pmid': '18250279', 'type': 'BACKGROUND', 'citation': 'Reynolds HR, Hochman JS. Cardiogenic shock: current concepts and improving outcomes. Circulation. 2008 Feb 5;117(5):686-97. doi: 10.1161/CIRCULATIONAHA.106.613596. No abstract available.'}, {'pmid': '15135197', 'type': 'BACKGROUND', 'citation': 'Vasquez A, Kern KB, Hilwig RW, Heidenreich J, Berg RA, Ewy GA. Optimal dosing of dobutamine for treating post-resuscitation left ventricular dysfunction. Resuscitation. 2004 May;61(2):199-207. doi: 10.1016/j.resuscitation.2004.01.002.'}, {'pmid': '884803', 'type': 'BACKGROUND', 'citation': 'Leier CV, Webel J, Bush CA. The cardiovascular effects of the continuous infusion of dobutamine in patients with severe cardiac failure. Circulation. 1977 Sep;56(3):468-72. doi: 10.1161/01.cir.56.3.468.'}, {'pmid': '12383572', 'type': 'BACKGROUND', 'citation': "Metra M, Nodari S, D'Aloia A, Muneretto C, Robertson AD, Bristow MR, Dei Cas L. Beta-blocker therapy influences the hemodynamic response to inotropic agents in patients with heart failure: a randomized comparison of dobutamine and enoximone before and after chronic treatment with metoprolol or carvedilol. J Am Coll Cardiol. 2002 Oct 2;40(7):1248-58. doi: 10.1016/s0735-1097(02)02134-4."}, {'pmid': '8277087', 'type': 'BACKGROUND', 'citation': "Wynsen JC, O'Brien PD, Warltier DC. Zatebradine, a specific bradycardic agent, enhances the positive inotropic actions of dobutamine in ischemic myocardium. J Am Coll Cardiol. 1994 Jan;23(1):233-41. doi: 10.1016/0735-1097(94)90526-6."}, {'pmid': '8547205', 'type': 'BACKGROUND', 'citation': 'Aidonidis I, Brachmann J, Rizos I, Zacharoulis A, Stavridis I, Toutouzas P, Kubler W. Electropharmacology of the bradycardic agents alinidine and zatebradine (UL-FS 49) in a conscious canine ventricular arrhythmia model of permanent coronary artery occlusion. Cardiovasc Drugs Ther. 1995 Aug;9(4):555-63. doi: 10.1007/BF00878087.'}, {'pmid': '8982692', 'type': 'BACKGROUND', 'citation': 'Hettrick DA, Pagel PS, Lowe D, Tessmer JP, Warltier DC. Increases in inotropic state without change in heart rate: combined use of dobutamine and zatebradine in conscious dogs. Eur J Pharmacol. 1996 Dec 5;316(2-3):237-44. doi: 10.1016/s0014-2999(96)00688-7.'}, {'pmid': '9265927', 'type': 'BACKGROUND', 'citation': 'Neustein SM, Dimich I, Shiang H, Mezrow C. Role of zatebradine and propranolol in attenuation of tachycardia produced by dobutamine in pigs. Acta Anaesthesiol Scand. 1997 Aug;41(7):849-52. doi: 10.1111/j.1399-6576.1997.tb04799.x.'}, {'pmid': '19559207', 'type': 'BACKGROUND', 'citation': 'Zhang Y, Mazgalev TN. Cardiac vagal stimulation eliminates detrimental tachycardia effects of dobutamine used for inotropic support. Ann Thorac Surg. 2009 Jul;88(1):117-22. doi: 10.1016/j.athoracsur.2009.04.009.'}, {'pmid': '15301560', 'type': 'BACKGROUND', 'citation': 'DiFrancesco D, Camm JA. Heart rate lowering by specific and selective I(f) current inhibition with ivabradine: a new therapeutic perspective in cardiovascular disease. Drugs. 2004;64(16):1757-65. doi: 10.2165/00003495-200464160-00003.'}, {'pmid': '18757088', 'type': 'BACKGROUND', 'citation': 'Fox K, Ford I, Steg PG, Tendera M, Ferrari R; BEAUTIFUL Investigators. Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial. Lancet. 2008 Sep 6;372(9641):807-16. doi: 10.1016/S0140-6736(08)61170-8. Epub 2008 Aug 29.'}, {'pmid': '20801500', 'type': 'BACKGROUND', 'citation': 'Swedberg K, Komajda M, Bohm M, Borer JS, Ford I, Dubost-Brama A, Lerebours G, Tavazzi L; SHIFT Investigators. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. Lancet. 2010 Sep 11;376(9744):875-85. doi: 10.1016/S0140-6736(10)61198-1.'}, {'pmid': '26967048', 'type': 'BACKGROUND', 'citation': "Henri C, O'Meara E, De Denus S, Elzir L, Tardif JC. Ivabradine for the treatment of chronic heart failure. Expert Rev Cardiovasc Ther. 2016;14(5):553-61. doi: 10.1586/14779072.2016.1165092. Epub 2016 Mar 28."}, {'pmid': '21875858', 'type': 'BACKGROUND', 'citation': "Tardif JC, O'Meara E, Komajda M, Bohm M, Borer JS, Ford I, Tavazzi L, Swedberg K; SHIFT Investigators. Effects of selective heart rate reduction with ivabradine on left ventricular remodelling and function: results from the SHIFT echocardiography substudy. Eur Heart J. 2011 Oct;32(20):2507-15. doi: 10.1093/eurheartj/ehr311. Epub 2011 Aug 29."}, {'pmid': '22075752', 'type': 'BACKGROUND', 'citation': 'Fang Y, Debunne M, Vercauteren M, Brakenhielm E, Richard V, Lallemand F, Henry JP, Mulder P, Thuillez C. Heart rate reduction induced by the if current inhibitor ivabradine improves diastolic function and attenuates cardiac tissue hypoxia. J Cardiovasc Pharmacol. 2012 Mar;59(3):260-7. doi: 10.1097/FJC.0b013e31823e5e01.'}, {'pmid': '14981003', 'type': 'BACKGROUND', 'citation': 'Mulder P, Barbier S, Chagraoui A, Richard V, Henry JP, Lallemand F, Renet S, Lerebours G, Mahlberg-Gaudin F, Thuillez C. Long-term heart rate reduction induced by the selective I(f) current inhibitor ivabradine improves left ventricular function and intrinsic myocardial structure in congestive heart failure. Circulation. 2004 Apr 6;109(13):1674-9. doi: 10.1161/01.CIR.0000118464.48959.1C. Epub 2004 Feb 23.'}, {'pmid': '20962545', 'type': 'BACKGROUND', 'citation': 'Boldt A, Gergs U, Ponicke K, Simm A, Silber RE, Neumann J. Inotropic effects of ivabradine in the mammalian heart. Pharmacology. 2010;86(5-6):249-58. doi: 10.1159/000320454. Epub 2010 Oct 21.'}, {'pmid': '23933545', 'type': 'BACKGROUND', 'citation': "Reil JC, Tardif JC, Ford I, Lloyd SM, O'Meara E, Komajda M, Borer JS, Tavazzi L, Swedberg K, Bohm M. Selective heart rate reduction with ivabradine unloads the left ventricle in heart failure patients. J Am Coll Cardiol. 2013 Nov 19;62(21):1977-1985. doi: 10.1016/j.jacc.2013.07.027. Epub 2013 Aug 7."}, {'pmid': '18486549', 'type': 'BACKGROUND', 'citation': 'De Ferrari GM, Mazzuero A, Agnesina L, Bertoletti A, Lettino M, Campana C, Schwartz PJ, Tavazzi L. Favourable effects of heart rate reduction with intravenous administration of ivabradine in patients with advanced heart failure. Eur J Heart Fail. 2008 Jun;10(6):550-5. doi: 10.1016/j.ejheart.2008.04.005. Epub 2008 May 16.'}, {'pmid': '24922198', 'type': 'BACKGROUND', 'citation': 'Cavusoglu Y, Mert U, Nadir A, Mutlu F, Morrad B, Ulus T. Ivabradine treatment prevents dobutamine-induced increase in heart rate in patients with acute decompensated heart failure. J Cardiovasc Med (Hagerstown). 2015 Sep;16(9):603-9. doi: 10.2459/JCM.0000000000000033.'}, {'pmid': '23719030', 'type': 'BACKGROUND', 'citation': 'Roubille F, Lattuca B, Busseuil D, Leclercq F, Davy JM, Rheaume E, Tardif JC. Is ivabradine suitable to control undesirable tachycardia induced by dobutamine in cardiogenic shock treatment? Med Hypotheses. 2013 Aug;81(2):202-6. doi: 10.1016/j.mehy.2013.05.002. Epub 2013 May 26.'}, {'pmid': '21966292', 'type': 'BACKGROUND', 'citation': 'Franke J, Schmahl D, Lehrke S, Pribe R, Bekeredjian R, Doesch AO, Ehlermann P, Schnabel P, Katus HA, Zugck C. Adjuvant Use of Ivabradine in Acute Heart Failure due to Myocarditis. Case Rep Med. 2011;2011:203690. doi: 10.1155/2011/203690. Epub 2011 Sep 27.'}, {'pmid': '19547907', 'type': 'BACKGROUND', 'citation': 'Link A, Reil JC, Selejan S, Bohm M. Effect of ivabradine in dobutamine induced sinus tachycardia in a case of acute heart failure. Clin Res Cardiol. 2009 Aug;98(8):513-5. doi: 10.1007/s00392-009-0038-9. Epub 2009 Jun 23. No abstract available.'}, {'pmid': '20821020', 'type': 'BACKGROUND', 'citation': 'Vitale D, De Santis V, Guarracino F, Fontana A, Pellegrini F, Tritapepe L. Use of ivabradine in catecholamine-induced tachycardia after high-risk cardiac surgery. Clin Res Cardiol. 2010 Dec;99(12):853-5. doi: 10.1007/s00392-010-0208-9. Epub 2010 Sep 7. No abstract available.'}, {'pmid': '25129291', 'type': 'BACKGROUND', 'citation': 'Gallet R, Ternacle J, Damy T, Guendouz S, Bremont C, Seemann A, Gueret P, Dubois-Rande JL, Lim P. Hemodynamic effects of Ivabradine in addition to dobutamine in patients with severe systolic dysfunction. Int J Cardiol. 2014 Sep 20;176(2):450-5. doi: 10.1016/j.ijcard.2014.07.093. Epub 2014 Aug 1.'}, {'pmid': '20543134', 'type': 'BACKGROUND', 'citation': 'Borlaug BA, Nishimura RA, Sorajja P, Lam CS, Redfield MM. Exercise hemodynamics enhance diagnosis of early heart failure with preserved ejection fraction. Circ Heart Fail. 2010 Sep;3(5):588-95. doi: 10.1161/CIRCHEARTFAILURE.109.930701. Epub 2010 Jun 11.'}, {'pmid': '18313622', 'type': 'BACKGROUND', 'citation': 'Borlaug BA, Kass DA. Ventricular-vascular interaction in heart failure. Heart Fail Clin. 2008 Jan;4(1):23-36. doi: 10.1016/j.hfc.2007.10.001.'}], 'seeAlsoLinks': [{'url': 'http://medicontenidosporcile.files.wordpress.com/2016/03/curr-reserch-cardiol.pdf', 'label': 'article: Safety, tolerability and efficacy of ivabradine for control of sinus tachycardia in patients undergoing inotropic therapy'}]}, 'descriptionModule': {'briefSummary': 'This is a randomized, double blind, single center trial to study of the effects of Ivabradine vs. Placebo on patients hospitalized for Stage D heart failure (HF)/ and cardiogenic shock (CS) who will require continuous infusion of Dobutamine and have developed sinus tachycardia (ST) (heart rate \\>100 beats/min).\n\nThe aim of the study will be to assess the potential of Ivabradine to slow ST and improve hemodynamics in patients with stage D HF/CS on Dobutamine treatment.', 'detailedDescription': 'This study will explore the hypothesis that Ivabradine will decrease heart rate (HR) and improve hemodynamics in patients with advanced HF on inotropic treatment. This is a randomized, double blind, single center trial will include 40 consecutive patients admitted for Stage D HF/ CS who will require continuous infusion of Dobutamine and will develop ST (HR \\>100 beats/min).\n\nEligible patients will be randomized (1:1) using blocked randomization with random block sizes of 2 or 4 to start Ivabradine versus placebo. The procedure of randomization to receive either Ivabradine or placebo twice daily will be performed by computerized sequence generation. The hospital pharmacies will be responsible for drug randomization and dispensing, and the investigators and the patients will be blinded to the treatment option.\n\nIvabradine will be started 3 hours after Dobutamine initiation at dose 5 mg and further increased in 12 hours to 7.5 mg bid if patient is stable with mean BP≥ 60 mmHg, systolic blood pressure ≥ 90 mmHg and HR ≥100 bpm. Increase of Ivabradine dosage will be individually stopped for reasons of safety if three episodes of minimal HRs of less than 70 beats per minute, or a drop in mean blood pressure \\< 60 mmHg or systolic blood pressure \\< 80 mmHg occur.\n\nHR, blood pressure and invasive hemodynamics will be monitored, along with standard right heart cath and echocardiogram measurements obtained.\n\nPatients will be followed for a total of 72 hours. The adverse events that will be collected include bradycardia, defined as a heart rate less than 70 bpm, hypotension defined as a systolic blood pressure less than 80 mmHg and any side effect requiring drug discontinuation or dose adjustment. Review of laboratory including renal, hepatic and hematologic counts will be reviewed for any significant changes due to the use of Ivabradine.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '99 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Provide written informed consent for the study\n* Have current diagnosis of Ischemic and/or non-ischemic cardiomyopathy\n* Left ventricular ejection fraction (LVEF) \\< 30% by echo during the screening\n* Sinus rhythm with HR ≥100 bpm\n* Systolic blood pressure ≥ 90 mmHg assessed by cuff sphygmomanometer\n* CI \\< 2.2 L/min/m2\n* Current symptom(s) of HF (New York Heart Association (NYHA) class IV) at Screening.\n* Absence of hypovolemia, defined as a central venous pressure ≥10 mmHg and pulmonary capillary occlusion pressure ≥15 mmHg before administration of Dobutamine\n\nExclusion Criteria:\n\n* Respiratory support with mechanical ventilation\n* Circulatory mechanical support\n* Atrial pacing with the presence of sick sinus syndrome or sino-atrial block\n* Second or third degree atrioventricular (AV) block,\n* Atrial fibrillation/flutter\n* Amiodarone treatment\n* Ventricular tachycardia\n* Acute coronary syndrome\n* Bilirubin \\> 2.5\n* Alanine aminotransferase (ALT) \\>60 IE/L,\n* Serum creatinine \\>2.5 g/ml)\n* Fever and significant infection\n* Pregnancy\n* Anemia, Hgb \\< 9.0\n* Patients required treated with severe cytochrome CYP3A4 inhibitors drugs Concomitant use of strong CYP3A4 inhibitors will be avoided during the study period'}, 'identificationModule': {'nctId': 'NCT03387605', 'briefTitle': 'Effect of Ivabradine in Stage D HF/Cardiogenic Shock Patients on Dobutamine', 'organization': {'class': 'OTHER', 'fullName': 'Loyola University'}, 'officialTitle': 'Effect of Ivabradine on Heart Rate and Hemodynamics in Patients With Stage D Heart Failure (HF)/Cardiogenic Shock on Dobutamine Treatment', 'orgStudyIdInfo': {'id': '209939'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Ivabradine', 'description': 'Initiation at dose 5 mg PO x 1 dose and further increased in 12 hours to 7.5 mg PO twice per day if patient is stable with mean BP≥ 60 mmHg, systolic blood pressure ≥ 90 mmHg and HR ≥100 bpm', 'interventionNames': ['Drug: Ivabradine']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo', 'description': 'Matching placebo given PO twice per day', 'interventionNames': ['Drug: Placebo']}], 'interventions': [{'name': 'Ivabradine', 'type': 'DRUG', 'otherNames': ['Corlanor'], 'description': 'ivabradine or placebo given orally 2 times daily for 72 hours', 'armGroupLabels': ['Ivabradine']}, {'name': 'Placebo', 'type': 'DRUG', 'description': 'matching placebo given 2 times daily for 72 hours', 'armGroupLabels': ['Placebo']}]}, 'contactsLocationsModule': {'locations': [{'zip': '60153', 'city': 'Maywood', 'state': 'Illinois', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Eugenia Raichlin, MD', 'role': 'CONTACT'}], 'facility': 'Loyola University Medical Center', 'geoPoint': {'lat': 41.8792, 'lon': -87.84312}}], 'centralContacts': [{'name': 'Eugenia Raichlin, MD', 'role': 'CONTACT', 'email': 'Eugenia.Raichlin@lumc.edu', 'phone': '708 327-2738'}, {'name': 'Max Liebo, MD', 'role': 'CONTACT', 'email': 'mliebo@lumc.edu', 'phone': '708 327-2738'}], 'overallOfficials': [{'name': 'Eugenia Raichlin, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Loyola University'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Loyola University', 'class': 'OTHER'}, 'collaborators': [{'name': 'Amgen', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Associate Professor', 'investigatorFullName': 'Eugenia Raichlin', 'investigatorAffiliation': 'Loyola University'}}}}