Anthracycline-induced Cardiotoxicity, Cardiotoxicity, Chemotherapy, Lymphoma
Conditions
Keywords
anthracycline, left ventricular dysfunction, cardiotoxicity, SGLT inhibitors, prevention
Brief summary
This project aims to determine the benefits of the dual SGLT1/2 inhibition as prophylactic treatment to prevent anthracycline-related cardiotoxicity.
Interventions
DRUGSotagliflozin
Sotagliflozin 400mg starting prior to the first scheduled anthracycline infusion
DRUGPlacebo
Placebo starting prior to the first scheduled anthracycline infusion
Sponsors
Icahn School of Medicine at Mount Sinai
American Heart Association
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients ≥ 18 years * Newly diagnosed lymphoma * Scheduled to receive high-dose anthracycline (cumulative dose ≥ 300 mg/m2) * Eastern Cooperative Oncology Group (ECOG) performance status 0-3
Exclusion criteria
* Prior anthracycline treatment * Previous malignancy requiring any chemotherapy or radiotherapy * Previous treatment with SGLT2i (eg due to T2DM) or SGLT1/2i * Previous heart failure (HF patients should already be on SGLT2i as per guidelines) * LVEF\<40% (even in the absence of HF): * Pregnancy or breastfeeding * Standard contraindication to MRI (claustrophobia, non-MRI compatible devices)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Left Ventricular Ejection Fraction (LVEF) by Cardiac MRI | Baseline and end of study, one month after completion of anthracycline treatment, up to 9-10 months. | LVEF is a measure of contractility of the heart (strength of contraction). Normal values are between 55-65%. It is the most widely used parameter by physicians worldwide to measure cardiac contractility. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Longitudinal Strain of Left Ventricle (LV) | Baseline and end of study, one month after completion of anthracycline treatment, up to 9-10 months. | Longitudinal strain is the deformation of a material per unit length, defined as the ratio of change in length to the original length in the direction of an applied load. It measures how much an object stretches (tensile) or compresses (compressive) along its axis Longitudinal strain is an echocardiographic technique that quantifies the percentage of systolic shortening of the heart muscle from base to apex. It is a highly sensitive indicator of left ventricular function, detecting subclinical, early myocardial dysfunction (e.g., in cardio-oncology) often before the ejection fraction (LVEF) drops. Normal GLS values are typically \>18%. |
| LVEF by 3D-Echocardiography | Baseline and end of study, one month after completion of anthracycline treatment, up to 9-10 months. | LVEF is a measure of contractility of the heart (strength of contraction). Normal values are between 55-65%. It is the most widely used parameter by physicians worldwide to measure cardiac contractility. |
| LV Volumes by MRI | Baseline and end of study, one month after completion of anthracycline treatment, up to 9-10 months. | LV volumes measure how enlarged the heart is. Chemotherapy destroys cardiac muscle and enlarges the heart (ie. increases LV volumes). The higher the LV volumes, the more damage by chemotherapy. |
| LV Mass by MRI | Baseline and end of study, one month after completion of anthracycline treatment, up to 9-10 months. | LV mass measures the amount of cardiac muscle. Chemotherapy destroys cardiac muscle. The lower the LV mass, the more damage by chemotherapy. |
| LV Longitudinal Strains by MRI | Baseline and end of study, one month after completion of anthracycline treatment, up to 9-10 months. | Longitudinal strain is the deformation of a material per unit length, defined as the ratio of change in length to the original length in the direction of an applied load. It measures how much an object stretches (tensile) or compresses (compressive) along its axis Longitudinal strain is an echocardiographic technique that quantifies the percentage of systolic shortening of the heart muscle from base to apex. It is a highly sensitive indicator of left ventricular function, detecting subclinical, early myocardial dysfunction (e.g., in cardio-oncology) often before the ejection fraction (LVEF) drops. Normal GLS values are typically \>18%. |
| 6-Minute Walk Test (6MWT) | Baseline and end of study, one month after completion of anthracycline treatment, up to 9-10 months. | The 6MWT assesses endurance and ability to walk over longer distances. The 6MWT was first described as a field test for physical fitness in 1963 and then as a 12-minute walk test in people with chronic bronchitis. The 6MWT was found to perform as well as the 12-minute walk, and is now used to assess the submaximal level of functional performance at a similar level required for daily physical activities. |
| NT-ProBNP | Baseline and end of study, one month after completion of anthracycline treatment, up to 9-10 months. | NT-ProBNP is a plasma biomarker of cardiac stress, cardiac tension and severity of heart failure. The higher the NT-ProBNP level, the more severe the heart failure induced by chemotherapy. |
| Troponin I | Baseline and end of study, one month after completion of anthracycline treatment, up to 9-10 months. | Troponin I is a plasma biomarker of cardiac injury and cardiac damage. The higher the troponin levels, the more cardiac damage induced by chemotherapy. |
Countries
United States
Contacts
CONTACTCarlos G Santos-Gallego, MD
CONTACTJuan Antonio Requena-Ibanez
PRINCIPAL_INVESTIGATORCarlos G Santos-Gallego, MD
Icahn School of Medicine at Mount Sinai
PRINCIPAL_INVESTIGATORSantos-Gallego, MD
Icahn School of Medicine at Mount Sinai
Outcome results
None listed