Ignite Creation Date:
2025-12-25 @ 3:29 AM
Ignite Modification Date:
2025-12-26 @ 2:10 AM
Study NCT ID:
NCT06888505
Status:
COMPLETED
Last Update Posted:
2025-09-18
First Post:
2025-03-03
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Dapagliflozin to Prevent Anthracycline-Induced Cardiotoxicity
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D066126', 'term': 'Cardiotoxicity'}], 'ancestors': [{'id': 'D006331', 'term': 'Heart Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D064420', 'term': 'Drug-Related Side Effects and Adverse Reactions'}, {'id': 'D064419', 'term': 'Chemically-Induced Disorders'}, {'id': 'D011832', 'term': 'Radiation Injuries'}, {'id': 'D014947', 'term': 'Wounds and Injuries'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C529054', 'term': 'dapagliflozin'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR'], 'maskingDescription': 'This is a double-blind, placebo-controlled trial in which participants, care providers, investigators, and outcomes assessors are blinded to treatment allocation. Randomization and treatment allocation will be conducted through a centralized system, and placebo tablets will be matched to ensure blinding.'}, 'primaryPurpose': 'PREVENTION', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'This study is a randomized, double-blind, placebo-controlled trial investigating the efficacy of Dapagliflozin in preventing chemotherapy-induced cardiotoxicity in cancer patients receiving anthracycline-based chemotherapy.'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 90}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2024-09-01', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-09', 'completionDateStruct': {'date': '2025-09-06', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2025-09-12', 'studyFirstSubmitDate': '2025-03-03', 'studyFirstSubmitQcDate': '2025-03-20', 'lastUpdatePostDateStruct': {'date': '2025-09-18', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2025-03-21', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2025-09-01', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Left Ventricular Function (Systolic and Diastolic)', 'timeFrame': 'Evaluated at baseline and 4 months after initiation of chemotherapy.', 'description': 'Echocardiographic assessment of left ventricular systolic function (LVEF) and diastolic function (E/A ratio, diastolic dysfunction grade) to detect anthracycline-induced cardiotoxicity.Measurement Tool: Echocardiography (using a 2D echocardiogram).'}], 'secondaryOutcomes': [{'measure': 'Cardiac Troponin I Levels', 'timeFrame': 'Evaluated at baseline and 4 months after initiation of chemotherapy.', 'description': 'Measurement of serum Troponin I levels to assess myocardial injury and cardiac stress in patients undergoing chemotherapy.\n\nMeasurement Tool: Chemiluminescent Immunoassay (CLIA).'}, {'measure': 'NT-proBNP Levels', 'timeFrame': 'Evaluated at baseline and 4 months after initiation of chemotherapy.', 'description': 'Measurement of serum NT-proBNP levels as an indicator of cardiac stress and dysfunction.\n\nMeasurement Tool: Chemiluminescent Immunoassay (CLIA).'}, {'measure': 'Galectin-3 Levels', 'timeFrame': 'Evaluated at baseline and 4 months after initiation of chemotherapy.', 'description': 'Measurement of serum Galectin-3 levels to evaluate its role in oxidative stress, apoptosis, and tissue remodeling.\n\nMeasurement Tool: Enzyme-Linked Immunosorbent Assay (ELISA).'}, {'measure': 'CA 15-3 Levels', 'timeFrame': 'Evaluated at baseline and 4 months after initiation of chemotherapy.', 'description': 'Measurement of serum CA 15-3 levels to monitor breast cancer cell proliferation.\n\nMeasurement Tool: Chemiluminescent immunoassay'}, {'measure': 'Kidney Function Tests', 'timeFrame': 'Evaluated at baseline and 4 months after initiation of chemotherapy.', 'description': 'Monitoring of serum creatinine and blood urea nitrogen (BUN) to assess renal function and potential nephrotoxicity related to chemotherapy or Dapagliflozin.\n\nMeasurement Tool: Automated Biochemical Analyzer for serum creatinine and BUN.'}, {'measure': 'Complete Blood Count (CBC)', 'timeFrame': 'Evaluated at baseline and 4 months after initiation of chemotherapy.', 'description': 'Monitoring of hematological parameters (e.g., hemoglobin, white blood cells, platelets) to assess overall health, immune function, and tolerability of treatment.\n\nMeasurement Tool: Automated Hematology Analyzer (Beckman Coulter analyzers).'}, {'measure': 'Liver Function Tests (LFTs)', 'timeFrame': 'Evaluated at baseline and 4 months after initiation of chemotherapy.', 'description': 'Monitoring of liver enzymes (e.g., ALT, AST, alkaline phosphatase, bilirubin) to assess liver function and potential hepatotoxicity due to chemotherapy or Dapagliflozin.\n\nMeasurement Tool: Chemiluminescent Immunoassay'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['cardiotoxicity', 'Anthracycline-induced cardiotoxicity', 'Dapagliflozin', 'SGLT2 inhibitors', 'cardio-oncology', 'Cardiac biomarkers in chemotherapy', 'Heart failure in cancer patients'], 'conditions': ['Anthracyclines-Induced Cardiotoxicity', 'Cardiotoxicity']}, 'descriptionModule': {'briefSummary': "Brief Summary Anthracyclines (e.g., doxorubicin) are effective anticancer agents but can cause dose-dependent, often irreversible cardiotoxicity via oxidative stress, mitochondrial dysfunction, and cardiomyocyte apoptosis. Trastuzumab is also associated with left-ventricular dysfunction, typically reversible. The original protocol planned cohorts for both drug classes; however, no trastuzumab patients were enrolled due to feasibility, and the final study focused exclusively on anthracycline-treated patients.\n\nDapagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor approved for diabetes and heart failure, has cardioprotective properties beyond glycemic control (reduced oxidative stress, inflammation, and fibrosis). We evaluated whether dapagliflozin mitigates anthracycline-induced cardiotoxicity.\n\nThis randomized, double-blind, placebo-controlled trial enrolled 90 patients receiving anthracycline-based chemotherapy. Participants were randomized 1:1 to:\n\n1. dapagliflozin 10 mg orally once daily for 4 months plus standard chemotherapy; or\n2. matching placebo once daily for 4 months plus standard chemotherapy. Primary outcome: change in left ventricular ejection fraction (LVEF) and diastolic function (e.g., E/A ratio, e'/E/e', diastolic dysfunction grade) from baseline to 16 weeks after chemotherapy initiation, measured by echocardiography.\n\nSecondary outcomes: Troponin I, NT-proBNP, Galectin-3, CA 15-3, renal indices (creatinine, BUN, eGFR), and incidence of symptomatic cardiac dysfunction (e.g., heart failure, arrhythmias, myocardial infarction). Safety events related to chemotherapy or dapagliflozin were recorded and graded by CTCAE.\n\nAssessments were performed at two time points only-baseline (pre-chemotherapy) and 16 weeks after initiation of chemotherapy; adverse events were collected continuously through the 16-week study period.\n\nIf effective, dapagliflozin could represent a practical cardioprotective strategy for patients receiving anthracyclines, potentially improving cardiovascular outcomes without compromising cancer therapy.", 'detailedDescription': "Background and Rationale Chemotherapy-induced cardiotoxicity is a significant concern in cancer treatment, particularly with anthracyclines (e.g., doxorubicin). Anthracycline-induced cardiotoxicity is often irreversible, resulting from oxidative stress, mitochondrial dysfunction, and direct cardiomyocyte apoptosis.\n\nTrastuzumab (Herceptin) is another major cardiotoxic drug, though its effects are often reversible. The initial protocol was designed to include both anthracycline- and trastuzumab-treated patients. However, due to feasibility constraints, the trastuzumab cohort was not enrolled, and the final study focused solely on patients receiving anthracycline-based chemotherapy.\n\nDapagliflozin, a sodium-glucose co-transporter-2 (SGLT2) inhibitor, is primarily used for type 2 diabetes mellitus and heart failure with reduced ejection fraction (HFrEF). Emerging evidence suggests cardioprotective properties independent of glucose control, including:\n\nReduction of oxidative stress and myocardial fibrosis Improvement of mitochondrial efficiency and myocardial metabolism Reduction in systemic and myocardial inflammation Modulation of sodium and calcium handling in cardiomyocytes Given these mechanisms, dapagliflozin may provide a protective effect against anthracycline-induced cardiotoxicity, preserving cardiac function without compromising cancer treatment efficacy.\n\nStudy Design and Methodology This is a randomized, double-blind, placebo-controlled clinical trial designed to evaluate the cardioprotective effects of dapagliflozin in cancer patients undergoing anthracycline-based chemotherapy.\n\nStudy Sites Primary Location: Azadi Oncology Center affiliated with Hawler Medical University and the Duhok General Health Directorate.\n\nMulticenter expansion was considered, but all participants were recruited at the primary site.\n\nStudy Population Enrollment (Actual): 90 participants receiving anthracycline-based chemotherapy.\n\nRandomization ratio: 1:1 (45 patients per group). Intervention and Control Groups Control Group (n=45): Standard chemotherapy + placebo. Dapagliflozin Group (n=45): Standard chemotherapy + dapagliflozin (10 mg/day, oral) for four months.\n\nFollow-up Period Duration: 4 months from initiation of chemotherapy. Assessment intervals: Baseline (pre-chemotherapy) and 4 months (post-chemotherapy completion).\n\nPrimary outcome: Change in left ventricular ejection fraction (LVEF) and diastolic function-assessed by transmitral E/A ratio, average septal/lateral e', E/e', and graded per ASE/EACVI criteria-from baseline to 16 weeks after chemotherapy initiation, measured by echocardiography.\n\nSecondary Endpoints Cardiac Biomarkers: Troponin I, NT-proBNP, Galectin-3. Cancer Progression Marker: CA 15-3. Renal Function: Creatinine, BUN, eGFR. Adverse Events: Incidence of chemotherapy- and dapagliflozin-related adverse effects, graded per CTCAE.\n\nSafety and Monitoring Plan Echocardiography: Baseline and 4 months. Biomarkers: Baseline and 4 months. ECG: Performed if clinically indicated to detect arrhythmias or QT prolongation.\n\nAdverse Events: Monitored continuously throughout the 4-month treatment and follow-up, including risks of hypoglycemia, hypotension, dehydration, renal events, urinary tract infections, and ketoacidosis.\n\nStatistical Analysis Plan Sample Size: Originally planned for 100 patients, but 90 were enrolled (45 per group).\n\nComparative Analysis: Paired t-tests, Wilcoxon signed-rank tests (for non-parametric data), ANOVA for repeated measures where appropriate.\n\nMultivariate Regression: Adjusting for age, baseline cardiac function, and cumulative anthracycline dose.\n\nMissing Data: Addressed using multiple imputation to maintain robustness. Ethical Considerations Approved by Hawler Medical University Ethics Committee and the Duhok General Health Directorate.\n\nWritten informed consent obtained from all participants. Potential Impact If dapagliflozin proves effective, this study could support the use of SGLT2 inhibitors as a cardioprotective strategy in anthracycline-treated cancer patients, improving cardiovascular outcomes, long-term survival, and quality of life."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '70 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Histologically confirmed breast cancer (or other cancers as relevant to the study).\n* Age 18-70 years.\n* Planned treatment with anthracycline-based chemotherapy\n* Normal kidney function, defined as serum creatinine 0.6-1.2 mg/dL.\n* Normal liver function, defined as ALT and AST 10-40 U/L.\n* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.\n* Willingness to participate and provide written informed consent.\n\nExclusion Criteria:\n\n* History of symptomatic heart failure (NYHA class III-IV) or prior anthracycline-related cardiac dysfunction.\n* Previous use of Dapagliflozin.\n* Pregnancy or breastfeeding.\n* Severe renal impairment (eGFR \\< 30 mL/min/1.73m²).\n* Uncontrolled diabetes mellitus (HbA1c \\> 9%).\n* Active or recurrent urinary tract infections (UTIs) within the last 6 months.\n* Known hypersensitivity to Dapagliflozin or related compounds.\n* Concurrent participation in another clinical trial investigating cardioprotective agents.'}, 'identificationModule': {'nctId': 'NCT06888505', 'acronym': 'DAPA-AIC', 'briefTitle': 'Dapagliflozin to Prevent Anthracycline-Induced Cardiotoxicity', 'organization': {'class': 'OTHER', 'fullName': 'Hawler Medical University'}, 'officialTitle': 'Mitigating Anthracycline-Induced Cardiac Toxicity With Dapagliflozin: A Randomized, Double-Blind, Placebo-Controlled Trial of 10 mg Daily for Four Months', 'orgStudyIdInfo': {'id': 'HSaeed'}, 'secondaryIdInfos': [{'id': 'Hawler Medical University', 'type': 'OTHER', 'domain': 'REC NO.: Meeting Code: 7, Paper Code: 4 Date: 27/05/2024'}, {'id': 'Duhok Directorate of Health', 'type': 'OTHER', 'domain': 'Ethics Committee NO.: 31072024-6-17 Date: 31/07/2024'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Dapagliflozin Arm', 'description': 'Participants in this arm received dapagliflozin 10 mg orally once daily in addition to their standard anthracycline-based chemotherapy regimen.\n\nDapagliflozin was continued daily for four months (throughout the chemotherapy treatment period).\n\nThe study evaluated its potential cardioprotective effects against anthracycline-induced cardiac toxicity using echocardiography, cardiac biomarkers, and safety monitoring.', 'interventionNames': ['Drug: Dapagliflozin (Forxiga)']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Control Arm', 'description': "Participants in this arm received a placebo tablet identical in appearance, dosage form, frequency, and duration to dapagliflozin.\n\nThe placebo was administered orally once daily for four months, alongside the participant's standard anthracycline-based chemotherapy regimen.\n\nThe placebo contained no active ingredients and served as the control to evaluate the cardioprotective efficacy of dapagliflozin.", 'interventionNames': ['Other: Placebo']}], 'interventions': [{'name': 'Dapagliflozin (Forxiga)', 'type': 'DRUG', 'otherNames': ['Farxiga'], 'description': 'Participants in the dapagliflozin arm received dapagliflozin 10 mg tablets, administered orally once daily for 4 months, in addition to their standard anthracycline-based chemotherapy regimen. This treatment was given continuously throughout the chemotherapy period to evaluate its cardioprotective effects against anthracycline-induced cardiac toxicity.', 'armGroupLabels': ['Dapagliflozin Arm']}, {'name': 'Placebo', 'type': 'OTHER', 'otherNames': ['Inactive tablet'], 'description': "Participants in the control arm received a placebo tablet identical in appearance, dosage form, frequency, and duration to dapagliflozin, but containing no active ingredients. The placebo was administered orally once daily for 4 months alongside the participant's standard anthracycline-based chemotherapy regimen and served as the control to evaluate the cardioprotective efficacy of dapagliflozin.", 'armGroupLabels': ['Control Arm']}]}, 'contactsLocationsModule': {'locations': [{'zip': '42001', 'city': 'Dihok', 'country': 'Iraq', 'facility': 'Azadi Oncology Centre', 'geoPoint': {'lat': 36.86608, 'lon': 42.9879}}], 'overallOfficials': [{'name': 'Hakar A Saeed, M.Sc', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University of Zakho'}, {'name': 'Nidhal A Mohammed Ali, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Hawler Medical University'}, {'name': 'Ramadhan T Othman, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University of Duhok'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO', 'description': 'At this time, individual participant data (IPD) will not be shared publicly. The data will be kept confidential to ensure participant privacy and comply with ethical and regulatory requirements, including those related to informed consent and data protection. Access to the data may be considered for future collaborations under strict ethical guidelines and approval from the relevant oversight bodies.'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Hawler Medical University', 'class': 'OTHER'}, 'collaborators': [{'name': 'University of Zakho', 'class': 'UNKNOWN'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Principal Investigator; PhD Candidate, Hawler Medical University; Lecturer, University of Zakho', 'investigatorFullName': 'Hakar abdulkareem saeed', 'investigatorAffiliation': 'Hawler Medical University'}}}}