Ignite Creation Date:
2025-12-25 @ 5:05 AM
Ignite Modification Date:
2026-02-22 @ 4:53 PM
Study NCT ID:
NCT03794518
Status:
UNKNOWN
Last Update Posted:
2019-01-07
First Post:
2018-08-01
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Effect of Dapagliflozin Plus Low Dose Pioglitazone on Hospitalization Rate in Patients With HF and HFpEF
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D040242', 'term': 'Risk Reduction Behavior'}], 'ancestors': [{'id': 'D001519', 'term': 'Behavior'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000077205', 'term': 'Pioglitazone'}], 'ancestors': [{'id': 'D045162', 'term': 'Thiazolidinediones'}, {'id': 'D013844', 'term': 'Thiazoles'}, {'id': 'D013457', 'term': 'Sulfur Compounds'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D001393', 'term': 'Azoles'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'SINGLE', 'whoMasked': ['PARTICIPANT'], 'maskingDescription': 'Random process'}, 'primaryPurpose': 'HEALTH_SERVICES_RESEARCH', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Pioglitazone (15 mg) and dapagliflozin (10mg) vs Placebo'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 648}}, 'statusModule': {'overallStatus': 'UNKNOWN', 'lastKnownStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2019-03', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2018-07', 'completionDateStruct': {'date': '2021-12', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2019-01-04', 'studyFirstSubmitDate': '2018-08-01', 'studyFirstSubmitQcDate': '2019-01-04', 'lastUpdatePostDateStruct': {'date': '2019-01-07', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2019-01-07', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2021-09', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Time to first hospitalization for heart failure after starting intervention', 'timeFrame': '3 years', 'description': 'Hospitalization for heart failure will be defined as a hospitalization \\>24 hours requiring intravenous diuretic infusion.'}], 'secondaryOutcomes': [{'measure': 'Number of all cause mortality', 'timeFrame': '3 years', 'description': 'Composite outcome comprised of total mortality, incidence of acute coronary syndrome and non fatal CVA'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Risk Reduction']}, 'referencesModule': {'references': [{'pmid': '25241351', 'type': 'RESULT', 'citation': 'Alharbi NS, Almutari R, Jones S, Al-Daghri N, Khunti K, de Lusignan S. Trends in the prevalence of type 2 diabetes mellitus and obesity in the Arabian Gulf States: systematic review and meta-analysis. Diabetes Res Clin Pract. 2014 Nov;106(2):e30-3. doi: 10.1016/j.diabres.2014.08.019. Epub 2014 Sep 6.'}, {'pmid': '19896746', 'type': 'RESULT', 'citation': 'Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract. 2010 Jan;87(1):4-14. doi: 10.1016/j.diabres.2009.10.007. Epub 2009 Nov 6.'}, {'pmid': '27979896', 'type': 'RESULT', 'citation': 'American Diabetes Association. 9. Cardiovascular Disease and Risk Management. Diabetes Care. 2017 Jan;40(Suppl 1):S75-S87. doi: 10.2337/dc17-S012. No abstract available.'}, {'pmid': '18452784', 'type': 'RESULT', 'citation': 'Bahrami H, Bluemke DA, Kronmal R, Bertoni AG, Lloyd-Jones DM, Shahar E, Szklo M, Lima JA. Novel metabolic risk factors for incident heart failure and their relationship with obesity: the MESA (Multi-Ethnic Study of Atherosclerosis) study. J Am Coll Cardiol. 2008 May 6;51(18):1775-83. doi: 10.1016/j.jacc.2007.12.048.'}, {'pmid': '4835750', 'type': 'RESULT', 'citation': 'Kannel WB, Hjortland M, Castelli WP. Role of diabetes in congestive heart failure: the Framingham study. Am J Cardiol. 1974 Jul;34(1):29-34. doi: 10.1016/0002-9149(74)90089-7. No abstract available.'}, {'pmid': '15277411', 'type': 'RESULT', 'citation': 'Nichols GA, Gullion CM, Koro CE, Ephross SA, Brown JB. The incidence of congestive heart failure in type 2 diabetes: an update. Diabetes Care. 2004 Aug;27(8):1879-84. doi: 10.2337/diacare.27.8.1879.'}, {'pmid': '14998615', 'type': 'RESULT', 'citation': 'Gustafsson I, Brendorp B, Seibaek M, Burchardt H, Hildebrandt P, Kober L, Torp-Pedersen C; Danish Investigatord of Arrhythmia and Mortality on Dofetilde Study Group. Influence of diabetes and diabetes-gender interaction on the risk of death in patients hospitalized with congestive heart failure. J Am Coll Cardiol. 2004 Mar 3;43(5):771-7. doi: 10.1016/j.jacc.2003.11.024.'}, {'pmid': '1386652', 'type': 'RESULT', 'citation': 'Pfeffer MA, Braunwald E, Moye LA, Basta L, Brown EJ Jr, Cuddy TE, Davis BR, Geltman EM, Goldman S, Flaker GC, et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. The SAVE Investigators. N Engl J Med. 1992 Sep 3;327(10):669-77. doi: 10.1056/NEJM199209033271001.'}, {'pmid': '16855265', 'type': 'RESULT', 'citation': 'Owan TE, Hodge DO, Herges RM, Jacobsen SJ, Roger VL, Redfield MM. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med. 2006 Jul 20;355(3):251-9. doi: 10.1056/NEJMoa052256.'}, {'pmid': '25398313', 'type': 'RESULT', 'citation': 'Shah SJ, Katz DH, Selvaraj S, Burke MA, Yancy CW, Gheorghiade M, Bonow RO, Huang CC, Deo RC. Phenomapping for novel classification of heart failure with preserved ejection fraction. Circulation. 2015 Jan 20;131(3):269-79. doi: 10.1161/CIRCULATIONAHA.114.010637. Epub 2014 Nov 14.'}, {'pmid': '26878357', 'type': 'RESULT', 'citation': 'Johnsson K, Johnsson E, Mansfield TA, Yavin Y, Ptaszynska A, Parikh SJ. Osmotic diuresis with SGLT2 inhibition: analysis of events related to volume reduction in dapagliflozin clinical trials. Postgrad Med. 2016 May;128(4):346-55. doi: 10.1080/00325481.2016.1153941. Epub 2016 Mar 2.'}, {'pmid': '23414743', 'type': 'RESULT', 'citation': 'Liu C, Liu T, Li G. Pioglitazone may offer therapeutic advantages in diabetes-related atrial fibrillation. Int J Cardiol. 2013 Sep 30;168(2):1603-5. doi: 10.1016/j.ijcard.2013.01.037. Epub 2013 Feb 12. No abstract available.'}, {'pmid': '25310928', 'type': 'RESULT', 'citation': 'Liu B, Wang J, Wang G. Beneficial effects of pioglitazone on retardation of persistent atrial fibrillation progression in diabetes mellitus patients. Int Heart J. 2014;55(6):499-505. doi: 10.1536/ihj.14-107. Epub 2014 Oct 14.'}, {'pmid': '25739882', 'type': 'RESULT', 'citation': 'Sulaiman K, Panduranga P, Al-Zakwani I, Alsheikh-Ali AA, AlHabib KF, Al-Suwaidi J, Al-Mahmeed W, AlFaleh H, Elasfar A, Al-Motarreb A, Ridha M, Bulbanat B, Al-Jarallah M, Bazargani N, Asaad N, Amin H. Clinical characteristics, management, and outcomes of acute heart failure patients: observations from the Gulf acute heart failure registry (Gulf CARE). Eur J Heart Fail. 2015 Apr;17(4):374-84. doi: 10.1002/ejhf.245. Epub 2015 Mar 4.'}, {'pmid': '28615237', 'type': 'RESULT', 'citation': 'Abdul-Ghani M, Migahid O, Megahed A, Adams J, Triplitt C, DeFronzo RA, Zirie M, Jayyousi A. Erratum. Combination Therapy With Exenatide Plus Pioglitazone Versus Basal/Bolus Insulin in Patients With Poorly Controlled Type 2 Diabetes on Sulfonylurea Plus Metformin: The Qatar Study. Diabetes Care 2017;40:325-331. Diabetes Care. 2017 Aug;40(8):1134. doi: 10.2337/dc17-er08d. Epub 2017 Jun 14. No abstract available.'}, {'pmid': '28096223', 'type': 'RESULT', 'citation': 'Abdul-Ghani M, Migahid O, Megahed A, Adams J, Triplitt C, DeFronzo RA, Zirie M, Jayyousi A. Combination Therapy With Exenatide Plus Pioglitazone Versus Basal/Bolus Insulin in Patients With Poorly Controlled Type 2 Diabetes on Sulfonylurea Plus Metformin: The Qatar Study. Diabetes Care. 2017 Mar;40(3):325-331. doi: 10.2337/dc16-1738. Epub 2017 Jan 17.'}]}, 'descriptionModule': {'briefSummary': 'The prevalence of type 2 diabetes mellitus (T2DM) in Qatar and nations worldwide has increased in recent decades into epidemic proportions. Cardiovascular (CVD) disease is the leading cause of death in T2DM patients. Approximately 80% of T2DM patients will die because of CV cause. Congestive heart failure (CHF) is a major cause of CV death in T2DM, and it also is responsible for significant morbidity and health care expenditure due to high rate of hospitalization for heart failure.', 'detailedDescription': 'Community based studies have demonstrated similar prevalence of HF with reduced ejection fraction (HFpEF) and HF with reduced LV function (HFrEF) in patients hospitalized for CHF. Moreover, the prevalence of HFrEF is declining over the past two decades, whereas that of HFpEF is progressively increasing. Progressive increase in obesity and T2DM prevalence is likely among the principal factors responsible for the steady increase in HFpEF prevalence.\n\nThe aims of the present study are to examine whether therapies that correct the myocardial metabolic abnormalities present in subjects with T2DM and diastolic dysfunction improve myocardial diastolic dysfunction and reduce the rate of hospitalizations in patients with HFpEF\n\nThe primary objective of the study is to examine the effect of combination therapy with pioglitazone (15 mg) plus dapagliflozin (10 mg) versus placebo on hospitalization for heart failure in patients with HFpEF.\n\nEligible subjects, who consent for participating in the study, will be seen by the study coordinator. Medical history and physical examination will be performed. Each subject will receive the following measurements:\n\nMedical history and physical examination including weight, height, waist, blood pressure and pulse.\n\nBlood tests:\n\nScreening: CBC, Blood chemistry, fasting plasma glucose concentration, HbA1c, renal and liver function, lipid profile, TSH, serum iron, iron biding capacity and ferritin.\n\nPlasma metabolites: ketone, lactate, bicarbonate, venous PH and plasma free fatty acid.\n\nHormones: insulin, C-peptide, glucagon, NT proBNP, angiotensin II, plasma renin activity, and aldosterone.\n\nInflammatory markers: adiponectin, hsCRP, IL-2, IL-6 and IL-12, F2-isoprostane, oxidized LDL.\n\nVascular Measurements: Measurement of pulse wave velocity, and central aortic pulse pressure, with sphygmocor.\n\nMeasurement of total body fat mass with Bioimpedence. Echocardiography\n\nPatients will be consented on the day of discharge or during the outpatient visit in the Cardiology Clinic. Consented patients will be referred to the CRC within one week to perform the echocardiography and vascular measurements. Patients will be asked to come to CRC after overnight fast and blood samples will be drawn for the above mentioned blood tests, after which echocardiography and vascular measurements will be performed.\n\nRandomization and Intervention:\n\nAfter completing the baseline studies, patients will be randomized into two groups to receive in a double blind fashion:\n\nGroup 1: combination of pioglitazone plus dapagliflozin, or Group 2: Placebo (Beta blockers, ACEI, ARB, and aldosterone )\n\nPatients in both groups will be matched for age, gender, BMI, HbA1c, systolic BP and LVEF. Randomization will be made by the pharmacist at the Heart Hospital and the randomization code will be maintained at the hospital pharmacy. Patients will be randomized in blocks of 4 while the group means are matched for the above parameters'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '80 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. Diagnosis of type 2 diabetes according to the ADA criteria.\n2. Drug naïve or on stable dose of antidiabetic therapy (oral agents and/or insulin) for 3 months preceding recruitment.\n3. Hospitalized for HFpEF (defined as hospitalization require intravenous diuresis) in the 6 months preceding recruitment.\n4. eGFR \\>60 ml/min\n5. LVEF \\>50%\n6. Presence of LV diastolic dysfunction in echocardiography\n\nWe have limited the inclusion criteria in the present study to T2DM patients with HFpEF and evidence of diastolic dysfunction by echocardiography in order to select a homogenous group of HFpEF patients with similar etiology, likely "metabolic HFpEF". We believe that this subgroup of HFpEF will benefit most from treatment with low dose pioglitazone (15 mg) plus dapagliflozin (10 mg).\n\nExclusion Criteria:\n\n1. Treatment with pioglitazone or SGLT2 inhibitor in the 3 months prior to recruitment.\n2. eGFR \\< 60 ml/min\n3. LVEF \\<50%;\n4. Valvular heart disease, ASD, VSD\n5. Chronic lung disease\n6. Cancer\n7. diabetes mellitus type 1\n8. patients with acute coronary syndrome, stroke or transient ischemic attack in the preceding 6 months\n9. pregnancy or lactation period'}, 'identificationModule': {'nctId': 'NCT03794518', 'briefTitle': 'Effect of Dapagliflozin Plus Low Dose Pioglitazone on Hospitalization Rate in Patients With HF and HFpEF', 'organization': {'class': 'INDUSTRY', 'fullName': 'Hamad Medical Corporation'}, 'officialTitle': 'Effect of Combination Therapy With Dapagliflozin Plus Low Dose Pioglitazone on Hospitalization Rate in Patients With Heart Failure and Preserved Left Ventricular Ejection Fraction', 'orgStudyIdInfo': {'id': 'IRGC-04-SI-17-116'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Pioglitazone Plus dapaglifliozin', 'description': 'Pioglitazone 15mg and dapaglifliozin 10mg together in T2DM patients having HF and HFpEF conditions', 'interventionNames': ['Drug: Pioglitazone Plus dapaglifliozin']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo', 'description': 'Beta blockers, ACEI, ARB, and aldosterone', 'interventionNames': ['Drug: Placebo']}], 'interventions': [{'name': 'Pioglitazone Plus dapaglifliozin', 'type': 'DRUG', 'description': 'Pioglitazone Plus dapaglifliozin', 'armGroupLabels': ['Pioglitazone Plus dapaglifliozin']}, {'name': 'Placebo', 'type': 'DRUG', 'description': '(Beta blockers, ACEI, ARB, and aldosterone )', 'armGroupLabels': ['Placebo']}]}, 'contactsLocationsModule': {'locations': [{'zip': '3050', 'city': 'Doha', 'country': 'Qatar', 'facility': 'Heart Hospital, Hamad Medical Coorporation', 'geoPoint': {'lat': 25.28545, 'lon': 51.53096}}], 'centralContacts': [{'name': 'Nidal Asaad, MD', 'role': 'CONTACT', 'email': 'nasaad@hamad.qa', 'phone': '44395578'}, {'name': 'Rajvir Singh, Ph.D', 'role': 'CONTACT', 'email': 'rsingh@hamad.qa', 'phone': '44390442'}], 'overallOfficials': [{'name': 'Nidal Asaad, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Heart Hospital, HMC, Doha, Qatar'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Hamad Medical Corporation', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}