Ignite Creation Date:
2024-07-17 @ 11:04 AM
Last Modification Date:
2024-10-26 @ 3:34 PM
Study NCT ID:
NCT06491680
Status:
RECRUITING
Last Update Posted:
2024-07-09
First Post:
2024-07-01
Brief Title:
Cardiotoxicity in Breast Cancer Patients
Sponsor:
Helwan University
Organization:
Helwan University
Study Overview
Official Title:
Evaluation of the Cardioprotective Effect of Dapagliflozin on Anthracyclines-Induced Cardiotoxicity in Breast Cancer Patients
Status:
RECRUITING
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The goal of this clinical trial is to learn if dapagliflozin drug has a cardioprotective effect against anthracyclines-induced cardiotoxicity It will also learn about the safety of dapagliflozin drug
Aim of the study
Evaluate cardioprotective effect and safety of dapagliflozin against anthracyclines-induced cardiotoxicity
The main questions it aims to answer are
1 Does the drug lower the cardiotoxicity which induced by anthracyclines
2 What medical problems do participants have when taking dapagliflozin drug
Treatment
1 Anthracyclines by 4 cycles included doxorubicin 50-60 mgm2 with cyclophosphamide 600 mg as a combination or epirubicin 90-100 mgm2 with cyclophosphamide 600 mg as a combination
2 Dapagliflozin 10 mg tablet orally once daily Started 7 days before the first cycle of anthracyclines till the end of last anthracyclines dose
Aim of the study
Evaluate cardioprotective effect and safety of dapagliflozin against anthracyclines-induced cardiotoxicity
The main questions it aims to answer are
1 Does the drug lower the cardiotoxicity which induced by anthracyclines
2 What medical problems do participants have when taking dapagliflozin drug
Treatment
1 Anthracyclines by 4 cycles included doxorubicin 50-60 mgm2 with cyclophosphamide 600 mg as a combination or epirubicin 90-100 mgm2 with cyclophosphamide 600 mg as a combination
2 Dapagliflozin 10 mg tablet orally once daily Started 7 days before the first cycle of anthracyclines till the end of last anthracyclines dose
Detailed Description:
Breast cancer is a malignant tumor that originates in the cells of the breast tissue It is the most common cancer in women worldwide accounting for 242 of all cancer cases among women
According to the latest World Health Organization statistics there were an estimated 23 million new cases of breast cancer in 2020 it is the second leading cause of cancer death in women after lung cancer
In Egypt breast cancer is the most common malignancy in women accounting for 388 of cancers in this population with the estimated number of breast cancer cases nearly 22700 in 2022 and forecasted to be approximately 46000 in 2050
Anthracyclines are well-established and highly effective anti-neoplastic agents used to treat several adult and pediatric cancers such as breast cancer leukemia lymphomas sarcomas and many others
Anthracycline-induced cardiotoxicity typically manifests as a reduction in left ventricular ejection fraction LVEF cardiomyopathy or symptomatic congestive heart failure CHF
Acute anthracycline cardiotoxicity - occurs during or immediately after a single dose of an anthracycline It may manifest as ventricular dysfunction ECG abnormalities and arrhythmias
Cardiotoxicity as a result of anthracycline chemotherapy has been linked to increased morbidity and mortality in breast cancer patients
In a recently published cohort study 2000 cancer survivors were monitored over 7 years The authors found that approximately one-third of deaths could be attributed to long-term cardiotoxicity
The specific mechanisms of anthracycline cardiotoxicity by Oxidative stress which in the presence of iron generates reactive oxygen species that cause lipid peroxidation of the cell membrane leading to damage of the cardiomyocytes inflammation by up-regulating the levels of various inflammatory mediators including interleukin-1 and tumor necrosis factor-α in the heart subsequently leading to cardiomyocyte damage In addition DOX activated the nod-like receptor pyrin domain containing 3 NLRP3 in cardiomyocytes promoting cardiomyocyte apoptosis and down-regulation of sirtuin and adenosine monophosphate-activated protein kinase AMPK activity which associated with cardiovascular disease by enhanced apoptosis and increased fibrosis The cardiomyocyte has always been considered the main cellular target of anthracycline toxic effect in the heart as their destruction results in the progressive development of cardiac dysfunction
Since anthracyclines is known to cause cardiotoxicity as a side effect a baseline echocardiogram ECHO is ordered for each patient before initiating anthracycline chemotherapy treatment as a standard of care Additionally follow-up ECHOs are conducted after starting the treatment cycles to detect any early signs of cardiotoxicity
Sodium Glucose co-transport inhibitors SGLT2i have demonstrated significant cardioprotective effects beyond their glucose-lowering capabilities Recent clinical studies have highlighted their ability to reduce cardiovascular events such as heart failure and myocardial infarction in diabetic patients
The cardioprotective benefits are thought to arise from multiple mechanisms including improved cardiac energy metabolism reduced blood pressure and decreased fluid overload As a result SGLT2i are emerging as a crucial therapeutic option not only for glycemic control but also for enhancing heart health marking a promising advancement in the management of cardiovascular risks
SGLT2i significantly reduces Systolic Blood Pressure SBP and arterial stiffness that leads to better oxygen consumption by myocardium and hence lowers the cardiac afterload It also helps in reducing the body weight slightly Additionally dapagliflozin also contributes by lowering the plasma volume by diuresis ie the increased excretion of sodium and glucose in urine Decreasing the inflammation pathway by modulating the activation of NLRP3 inflammasome thereby attenuating the synthesis of proinflammatory cytokines and reduced levels of tumor necrosis factor-α and interleukins decreasing oxidative Stress by attenuate the generation of reactive oxygen species and enhance antioxidant mechanisms by inhibiting NADPH oxidase nicotinamide adenine dinucleotide phosphate hydrogen and enhance energy metabolism by up-regulating the expression or activity of AMPK and sirtuins
In light of the demonstrated cardioprotective effects of SGLT2 inhibitors SGLT2i in heart failure patients these agents have been integrated into standard heart failure clinical guidelines irrespective of the patients diabetic status Considering the well-established cardiotoxicity associated with anthracycline use a thorough literature review was conducted to explore the potential of SGLT2i as adjunctive therapy to mitigate cardiac toxicity in breast cancer patients undergoing anthracycline-based chemotherapy However the search yielded only preclinical evidence which highlighted the promising role of dapagliflozin Consequently this clinical trial aims to evaluate the efficacy of dapagliflozin as adjunctive therapy in breast cancer patients receiving anthracyclines with a specific focus on preventing or delaying the onset of cardiotoxicity
According to the latest World Health Organization statistics there were an estimated 23 million new cases of breast cancer in 2020 it is the second leading cause of cancer death in women after lung cancer
In Egypt breast cancer is the most common malignancy in women accounting for 388 of cancers in this population with the estimated number of breast cancer cases nearly 22700 in 2022 and forecasted to be approximately 46000 in 2050
Anthracyclines are well-established and highly effective anti-neoplastic agents used to treat several adult and pediatric cancers such as breast cancer leukemia lymphomas sarcomas and many others
Anthracycline-induced cardiotoxicity typically manifests as a reduction in left ventricular ejection fraction LVEF cardiomyopathy or symptomatic congestive heart failure CHF
Acute anthracycline cardiotoxicity - occurs during or immediately after a single dose of an anthracycline It may manifest as ventricular dysfunction ECG abnormalities and arrhythmias
Cardiotoxicity as a result of anthracycline chemotherapy has been linked to increased morbidity and mortality in breast cancer patients
In a recently published cohort study 2000 cancer survivors were monitored over 7 years The authors found that approximately one-third of deaths could be attributed to long-term cardiotoxicity
The specific mechanisms of anthracycline cardiotoxicity by Oxidative stress which in the presence of iron generates reactive oxygen species that cause lipid peroxidation of the cell membrane leading to damage of the cardiomyocytes inflammation by up-regulating the levels of various inflammatory mediators including interleukin-1 and tumor necrosis factor-α in the heart subsequently leading to cardiomyocyte damage In addition DOX activated the nod-like receptor pyrin domain containing 3 NLRP3 in cardiomyocytes promoting cardiomyocyte apoptosis and down-regulation of sirtuin and adenosine monophosphate-activated protein kinase AMPK activity which associated with cardiovascular disease by enhanced apoptosis and increased fibrosis The cardiomyocyte has always been considered the main cellular target of anthracycline toxic effect in the heart as their destruction results in the progressive development of cardiac dysfunction
Since anthracyclines is known to cause cardiotoxicity as a side effect a baseline echocardiogram ECHO is ordered for each patient before initiating anthracycline chemotherapy treatment as a standard of care Additionally follow-up ECHOs are conducted after starting the treatment cycles to detect any early signs of cardiotoxicity
Sodium Glucose co-transport inhibitors SGLT2i have demonstrated significant cardioprotective effects beyond their glucose-lowering capabilities Recent clinical studies have highlighted their ability to reduce cardiovascular events such as heart failure and myocardial infarction in diabetic patients
The cardioprotective benefits are thought to arise from multiple mechanisms including improved cardiac energy metabolism reduced blood pressure and decreased fluid overload As a result SGLT2i are emerging as a crucial therapeutic option not only for glycemic control but also for enhancing heart health marking a promising advancement in the management of cardiovascular risks
SGLT2i significantly reduces Systolic Blood Pressure SBP and arterial stiffness that leads to better oxygen consumption by myocardium and hence lowers the cardiac afterload It also helps in reducing the body weight slightly Additionally dapagliflozin also contributes by lowering the plasma volume by diuresis ie the increased excretion of sodium and glucose in urine Decreasing the inflammation pathway by modulating the activation of NLRP3 inflammasome thereby attenuating the synthesis of proinflammatory cytokines and reduced levels of tumor necrosis factor-α and interleukins decreasing oxidative Stress by attenuate the generation of reactive oxygen species and enhance antioxidant mechanisms by inhibiting NADPH oxidase nicotinamide adenine dinucleotide phosphate hydrogen and enhance energy metabolism by up-regulating the expression or activity of AMPK and sirtuins
In light of the demonstrated cardioprotective effects of SGLT2 inhibitors SGLT2i in heart failure patients these agents have been integrated into standard heart failure clinical guidelines irrespective of the patients diabetic status Considering the well-established cardiotoxicity associated with anthracycline use a thorough literature review was conducted to explore the potential of SGLT2i as adjunctive therapy to mitigate cardiac toxicity in breast cancer patients undergoing anthracycline-based chemotherapy However the search yielded only preclinical evidence which highlighted the promising role of dapagliflozin Consequently this clinical trial aims to evaluate the efficacy of dapagliflozin as adjunctive therapy in breast cancer patients receiving anthracyclines with a specific focus on preventing or delaying the onset of cardiotoxicity
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None