Ignite Creation Date:
2025-12-25 @ 3:08 AM
Ignite Modification Date:
2026-03-04 @ 3:14 PM
Study NCT ID:
NCT04111133
Status:
RECRUITING
Last Update Posted:
2024-02-13
First Post:
2019-09-26
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Ivabradine in Cirrhotic Cardiomyopathy
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D018487', 'term': 'Ventricular Dysfunction, Left'}, {'id': 'D008103', 'term': 'Liver Cirrhosis'}, {'id': 'D006975', 'term': 'Hypertension, Portal'}], 'ancestors': [{'id': 'D018754', 'term': 'Ventricular Dysfunction'}, {'id': 'D006331', 'term': 'Heart Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}, {'id': 'D008107', 'term': 'Liver Diseases'}, {'id': 'D004066', 'term': 'Digestive System Diseases'}, {'id': 'D005355', 'term': 'Fibrosis'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, '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': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE', 'maskingDescription': 'Open Label'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 130}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2020-01-01', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-02', 'completionDateStruct': {'date': '2024-12', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2024-02-12', 'studyFirstSubmitDate': '2019-09-26', 'studyFirstSubmitQcDate': '2019-09-28', 'lastUpdatePostDateStruct': {'date': '2024-02-13', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2019-10-01', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2024-10', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Survival', 'timeFrame': '12 months', 'description': 'All cause mortality to be assessed'}], 'secondaryOutcomes': [{'measure': "Change in E/e' Ratio", 'timeFrame': '12 months', 'description': 'Echo parameter to be documented'}, {'measure': 'Change in renal function', 'timeFrame': '12 months'}, {'measure': 'Change in HRQoL', 'timeFrame': '12 months'}, {'measure': 'Change in neurohormonal markers- Brain natriuretic peptide, aldosterone, plasma renin activity', 'timeFrame': '12 months'}, {'measure': 'Number of Episodes of Cirrhosis related events', 'timeFrame': '12 months', 'description': 'New onset ascites, variceal bleeding,hepatorenal syndrome'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Cirrhotic cardiomyopathy', 'Left ventricular diatolic dysfunction', 'Carvedilol', 'Ivabradine'], 'conditions': ['Cirrhotic Cardiomyopathy', 'Left Ventricular Dysfunction', 'Cirrhosis, Liver', 'Portal Hypertension']}, 'referencesModule': {'references': [{'pmid': '31342529', 'type': 'RESULT', 'citation': 'Izzy M, VanWagner LB, Lin G, Altieri M, Findlay JY, Oh JK, Watt KD, Lee SS; Cirrhotic Cardiomyopathy Consortium. Redefining Cirrhotic Cardiomyopathy for the Modern Era. Hepatology. 2020 Jan;71(1):334-345. doi: 10.1002/hep.30875. Epub 2019 Oct 11.'}, {'pmid': '31305281', 'type': 'RESULT', 'citation': 'Premkumar M, Rangegowda D, Vyas T, Khumuckham JS, Shasthry SM, Thomas SS, Goyal R, Kumar G, Sarin SK. Carvedilol Combined With Ivabradine Improves Left Ventricular Diastolic Dysfunction, Clinical Progression, and Survival in Cirrhosis. J Clin Gastroenterol. 2020 Jul;54(6):561-568. doi: 10.1097/MCG.0000000000001219.'}, {'pmid': '35068798', 'type': 'RESULT', 'citation': 'Kaur H, Premkumar M. Diagnosis and Management of Cirrhotic Cardiomyopathy. J Clin Exp Hepatol. 2022 Jan-Feb;12(1):186-199. doi: 10.1016/j.jceh.2021.08.016. Epub 2021 Aug 21.'}]}, 'descriptionModule': {'briefSummary': 'A total of 130 patients with liver cirrhosis who fulfill the criteria of the study, and who have been found to have left ventricular diastolic dysfunction on a screening 2D echocardiography, will then be randomized by Block randomization technique, to two arms in a ratio 1:1(Group A) will receive carvedilol+ Ivabradine targeted therapy for heart rate reduction while Group B will receive Carvedilol alone; and the dosage of drug in the treatment arm will be titrated every week to achieve target heart rate of 50-60/ minute. Patients in the treatment arms, who are unable to tolerate carvedilol due to hypotension episodes, will be offered ivabradine alone to allow achievement of targeted heart rate reduction. All patients will be evaluated at 0,6, and 12 months. The end points will be clinical events, cardiac function improvement, renal function, and mortality.', 'detailedDescription': "The investigators have already demonstrated the role of targeted heart rate reduction in the management of LVDD in cirrhosis, but the previous study could not demonstrate the role of ivabradine alone in absence of betablocker therapy. This trial will be a validation cohort for the initial data obtained on this novel drug. The use of ivabradine can treat patients who do not tolerate betablocker therapy due to contraindications or adverse effects especially hypotension.\n\nDiagnosis of CCM will be as per 2020 CCMC criteria. CCM is defined as systolic or diastolic dysfunction in the absence of alternative cardiac pathology in concordance with the Cirrhotic Cardiomyopathy Consortium (CCMC) criteria. 9 Systolic dysfunction was defined as an ejection fraction (EF) ≤50% or an absolute value of GLS \\<18%. CCM will defined as presence of 3 of the following 4 criteria: septal early diastolic mitral annular flow velocity (e') \\<7 cm/s, early diastolic transmitral flow to early diastolic mitral annular velocity (E/e') ≥15, left atrial volume index (LAVI) \\>34 mL/m2, tricuspid jet maximum velocity \\>2.8 m/s, in the absence of pulmonary hypertension and the presence of measurable early to late diastolic transmitral flow velocity (E/A) ratio (E/A \\>2 = grade 3 \\& E/A 0.8-2 = grade 2 LVDD). Persons meeting only 2 criteria will be termed as indeterminate for LVDD grade."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '65 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Age range of 18-65 years\n* Cirrhosis, as diagnosed by histology or clinical, laboratory and USG findings,\n* LV diastolic dysfunction on 2D echocardiography\n\nExclusion Criteria:\n\n* Chronic renal disease\n* Patient already on beta blocker\n* Pregnancy and peripartum cardiomyopathy\n* Hypertension\n* Coronary artery disease\n* Valvular heart disease\n* Sick sinus syndrome/ Pacemaker\n* Cardiac rhythm disorder\n* Hypothyroidism\n* Hyperthyroidism\n* Portal vein thrombosis\n* Transjugular intrahepatic porto systemic shunt (TIPS) insertion\n* Hepatocellular carcinoma\n* Anemia Hb \\< 8gm/dl in females, and \\< 9 gm/dl in males'}, 'identificationModule': {'nctId': 'NCT04111133', 'briefTitle': 'Ivabradine in Cirrhotic Cardiomyopathy', 'organization': {'class': 'OTHER', 'fullName': 'Post Graduate Institute of Medical Education and Research, Chandigarh'}, 'officialTitle': "Efficacy of Carvedilol + Ivabradine vs Carvedilol Alone for Left Ventricular Diastolic Dysfunction in Chronic Liver Disease Patients and Its' Impact on Morbidity and Mortality; a Prospective Randomized Controlled Trial.", 'orgStudyIdInfo': {'id': 'INT/IEC/2019/001617'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Carvedilol + Ivabradine', 'interventionNames': ['Drug: Betablocker + ivabradine']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Carvedilol', 'interventionNames': ['Drug: Betablocker']}], 'interventions': [{'name': 'Betablocker + ivabradine', 'type': 'DRUG', 'description': 'Use of maximum tolerated dose of carvedilol and ivabradine to achieve therapeutic heart rate reduction (THR) to 55-65 beats per minute', 'armGroupLabels': ['Carvedilol + Ivabradine']}, {'name': 'Betablocker', 'type': 'DRUG', 'description': 'Use of maximum tolerated dose of carvedilol to achieve targeted heart rate reduction (THR) to 55-65 beats per minute (responder) or inability to reach THR (non responder) with maximum dose of carvedilol, maintaining a minimum MAP of 70 mmHg.', 'armGroupLabels': ['Carvedilol']}]}, 'contactsLocationsModule': {'locations': [{'zip': '160012', 'city': 'Chandigarh', 'state': 'Choose Any State/Province', 'status': 'RECRUITING', 'country': 'India', 'contacts': [{'name': 'Madhumita Premkumar', 'role': 'CONTACT'}], 'facility': 'Postgraduate Institute of Medical Education and Research', 'geoPoint': {'lat': 30.73629, 'lon': 76.7884}}], 'centralContacts': [{'name': 'Madhumita Premkumar, MD DM', 'role': 'CONTACT', 'email': 'drmadhumitap@gmail.com', 'phone': '01722756344'}], 'overallOfficials': [{'name': 'Radha K Dhiman, MD DM', 'role': 'STUDY_CHAIR', 'affiliation': 'Post Graduate Institute of Medical Education and Research, Chandigarh'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'UNDECIDED'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Post Graduate Institute of Medical Education and Research, Chandigarh', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Assistant Professor and Principal Investigator, Department of Hepatology', 'investigatorFullName': 'Madhumita Premkumar', 'investigatorAffiliation': 'Post Graduate Institute of Medical Education and Research, Chandigarh'}}}}