Cardioprotective Empagliflozin for Cancer Patients Receiving Doxorubicin

NCT06103279 | Unknown Phase 2 DMC

• 1 other identifier: Cardioprotective Empagliflozin
• Study Type: interventional
• Target: 40
• Locations: 0 countries
• Sites: N/A

Brief Summary

Doxorubicin induced cardiomyopathy is the most common and serious side effect associated with doxorubicin treatment in cancer patients receiving doxorubicin. Studies have been shown that Empagliflozin can reduce cardiovascular mortality and hospitalization for heart failure in patients with heart failure with or without diabetes and current clinical trials indicate that SGLT2 inhibitors protect against heart failure outcomes and can reduce cardiac remodeling even in patients without diabetes. Empagliflozin had beneficial effects on the outcome of the cardiomyopathy and also has anti-tumor activity in animal studies, but clinical studies are still lacking. We are going to investigate the cardioprotective effect of Empagliflozin against doxorubicin induced cardiomyopathy. Objective:

• Evaluate the prophylactic effect of using Empagliflozin "a selective inhibitor of the sodium glucose co-transporter 2 (SGLT2)" against doxorubicin induced cardiotoxicity in patients receiving doxorubicin-based chemotherapy.
• Monitor the safety of adding empagliflozin to doxorubicin-based chemotherapy.

Conditions

Cancer

Keywords

Empagliflozin; Doxorubicin OR Adriamycin; Cardiomyopathy OR Cardiotoxicity

Outcome Measures

Primary Outcomes (2)

• ''Cardiac troponin T''

  Monitoring the serum biomarker Cardiac troponin T at baseline and one time at the end of chemotherapy after the last dose of doxorubicin. "The incidence of troponin elevation above the threshold indicated by the manufacturer of the assay used by the local laboratories will be recorded."

  Baseline and one time at the end of chemotherapy (3 to 5 days after the last dose of doxorubicin).

• Echocardiography (ECHO)

  Initial evaluation of cardiac function guided by Echocardiography (ECHO) and clinical examination at baseline, after each 3 doses of doxorubicin-based chemotherapy and for follow up for 2 consecutive times every 3 months after the end of chemotherapy. "Cardiotoxicity or left ventricular dysfunction" will be defined as: a reduction of LV ejection fraction (LVEF) by 10% or more from baseline or with values lower than 50% at any follow up.

  Baseline, after each 3 doses of doxorubicin-based chemotherapy and 3 months after the end of chemotherapy.

Study Arms (2)

Empa Arm

EXPERIMENTAL

(Intervention group = 20 patients) \>\> will receive the standard chemotherapy protocol (DOX-based chemotherapy) plus Empagliflozin. Empagliflozin dose and duration: According to the Evidence-based doses of disease-modifying drugs in key randomized trials in patients with heart failure with reduced ejection fraction with or without diabetes, The recommended dose of empagliflozin is 10 mg once daily. 1 tablet once daily of continuously starting from 1 week before starting DOX till the end of last Dox-based chemotherapy dose according to the given chemotherapy protocol.

Drug: Empagliflozin 10 MG

Control Arm

NO INTERVENTION

(Control group = 20 patients) \>\> will receive the standard chemotherapy protocol (DOX-based chemotherapy) only.

Interventions

Empagliflozin 10 MG DRUG

1 tablet once daily of (EMPAGLIMAX® 10 mg) continuously starting from 1 week before starting doxorubicin till the end of last Dox-based chemotherapy dose according to the given chemotherapy protocol

Empa Arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Chemo-naive patients with a first diagnosis of cancer and indication for first-line therapy with doxorubicin-based chemotherapy.
• Patients intended to receive at least 4 cycles of doxorubicin or greater.
• No previous cardiac conditions (including ischemic heart disease and clinically important congenital or acquired valvular and myocardial diseases) and taking no cardiac-related drugs.
• An echocardiographic LVEF value ≥55%.
• Normal hepatic and renal function (bilirubin ≤1.5 mg/dL, creatinine ≤2.0 mg/dL).
• ECOG performance grade 0, 1 or 2.

You may not qualify if:

• Hypersensitivity / Allergy to Empagliflozin.
• Any condition that contraindicates chemotherapy (i.e., pregnancy, lactation).
• New-onset cardiac symptoms or presence of congestive heart failure symptoms or established (dilated, restrictive or hypertrophic) cardiomyopathy, coronary heart disease, moderate or severe aortic and/or mitral valve disease or atrial fibrillation detected by baseline echocardiography.
• Systemic hypertension, acute coronary syndrome or cardiac surgery within the last 3 months.
• Patients with known history or current treatment with cardiotoxic agents.
• Receiving radiation on the left side of body.
• History of rheumatic fever
• Alcohol abuse.
• Current participation in any other clinical investigation.
• End-stage renal disease or patients on dialysis.
• Patients with diabetic ketoacidosis or patients with type 1 diabetes mellitus.
• Glomerular Filtration Rate \<30ml/Kg/min.

Sponsors & Collaborators

• Ain Shams University: lead

Related Publications (16)

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  PMID: 17161256 RESULT

• Eliaa SG, Al-Karmalawy AA, Saleh RM, Elshal MF. Empagliflozin and Doxorubicin Synergistically Inhibit the Survival of Triple-Negative Breast Cancer Cells via Interfering with the mTOR Pathway and Inhibition of Calmodulin: In Vitro and Molecular Docking Studies. ACS Pharmacol Transl Sci. 2020 Nov 11;3(6):1330-1338. doi: 10.1021/acsptsci.0c00144. eCollection 2020 Dec 11.

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• Wang CY, Chen CC, Lin MH, Su HT, Ho MY, Yeh JK, Tsai ML, Hsieh IC, Wen MS. TLR9 Binding to Beclin 1 and Mitochondrial SIRT3 by a Sodium-Glucose Co-Transporter 2 Inhibitor Protects the Heart from Doxorubicin Toxicity. Biology (Basel). 2020 Oct 29;9(11):369. doi: 10.3390/biology9110369.

  PMID: 33138323 RESULT

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  PMID: 25948538 RESULT

MeSH Terms

Conditions

Neoplasms

Interventions

empagliflozin

Central Study Contacts

Abdelrahman Ahmed Abdelsalam Attia Mahmoud

CONTACT

00201008126620; abdelrahman.attia18@pharma.asu.edu.eg

Sara Mahmoud Zaki Shahin

CONTACT

00201127666522; sara.shahin@pharma.asu.edu.eg

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Teaching assistant

Model Details: The work is a prospective, randomized, controlled study. A total of 40 cancer patients who will receive DOX-based chemotherapy will be enrolled in the study These patients will be randomly assigned to either Group I or Group II (each group contains 20 patients) Group I: will receive the standard chemotherapy protocol (DOX-based chemotherapy) only. Group II: will receive the standard chemotherapy protocol (DOX-based chemotherapy) plus Empagliflozin.

Study Record Dates

• First Submitted: October 22, 2023
• First Posted: October 26, 2023
• Study Start: November 1, 2023
• Primary Completion: July 1, 2024
• Study Completion: August 1, 2024
• Last Updated: October 26, 2023

Record last verified: 2023-10