CardioPROTECTion with Dapagliflozin in Breast Cancer Patients Treated with AnthrAcycline - PROTECTAA TRIAL

Phase 3RecruitingNCT06304857

4th Military Clinical Hospital with Polyclinic, Poland188 enrolled

Overview

The purpose of this study is to evaluate the effect of dapagliflozin on the incidence of cancer therapeutics-related cardiac dysfunction in patients with breast cancer receiving anthracycline treatment.

This is a multicentre, randomised, double-blind, placebo-controlled phase III study, evaluating the effect of dapagliflozin versus placebo on prevention of cardiotoxicity in breast cancer patients undergoing anthracycline-based chemotherapy.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Enrollment

188

Conditions

Breast Cancer Heart Failure

Interventions

DapagliflozinDRUG

10 mg tablet q.d

PlaceboDRUG

tablet matching dapagliflozin 10 mg q.d

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age \> 18 years and \< 80 years. * Diagnosis of invasive breast cancer \[stage I-III\] and planned anthracycline treatment within 60 days. * Signed Informed Consent to participate in the study. Exclusion Criteria: * Urinary tract infection with the need for treatment with an antibiotic 48 hours before the scheduled start of anthracycline treatment. * Recognised heart failure or symptoms which, in the opinion of the investigator may be a symptom of undiagnosed heart failure. * Left ventricular ejection fraction \< 50% at the time of the screening. * Severe valvular heart disease. * A history of clinically significant arrhythmia, including atrial fibrillation regardless of type (at discretion of the investigator). * A history of stroke. * Cardiomyopathy: congenital, post-inflammatory, toxic, infiltrative (e.g. amyloidosis, sarcoidosis, haemochromatosis), postnatal or hypertrophic. * Pulmonary hypertension. * Uncontrolled arterial pressure or systolic pressure \< 80 mmHg at screening (at the discretion of the investigator). * BMI \> 40 kg/m2. * Diagnosed type 1 or type 2 diabetes or fasting glucose ≥ 126 mg/dl or HbA1C ≥ 6,5% (48 mmol/mol). * Pregnancy or breastfeeding. * Lack of compliance to use highly effective method of birth control. * Expected or possible treatment with epirubicin or liposomal doxorubicin within 12 months. * Taking another study drug or drugs from the group of SGLT2 inhibitors up to 6 months before the screening visit. * Taking semaglutide, liraglutide and metformin during the 30 days preceding the screening visit. * eGFR \< 25 ml/min/1.73m2 according to CKD EPI. * Life expectancy \< 12 months or cancer disease stage IV according to the TNM classification. * Alanine transaminase or aspartate transaminase levels above 2.5 times the local norm. * Anemia with Hemoglobin \< 9 g/dl. * Kidney failure \> G2 (according to KDIGO classification). * Liver disorders, Child-Pugh score \> 4. * Known, active infections with HIV, HBV, HCV, tuberculosis. * Any other condition which, in the opinion of the investigator, makes it impossible to fulfill the requirements for participation in this study.

Locations (3)

4th Military Clinical Hospital with Polyclinic

Wroclaw, Lower Silesian Voivodeship, Poland

RECRUITING

Lower Silesian Centre for Oncology, Lung Diseases and Hematology

Wroclaw, Lower Silesian Voivodeship, Poland

RECRUITING

Military Medical Institute

Warsaw, Masovian Voivodeship, Poland

RECRUITING

Outcomes

Primary Outcomes

Primary efficacy composite endpoint (cancer therapeutics related cardiac dysfunction) at 12 months.

Incidence of cancer therapeutics related cardiac dysfunction defined as: 1. the appearance of heart failure symptoms (NYHA class I-IV) due to an impairment of heart function or structure within 12 months; or 2. asymptomatic decrease in left ventricular ejection fraction \> 10% after 12 months; or 3. asymptomatic decrease in left ventricular ejection fraction \< 10% but up to 40-49% after 12 months; or 4. asymptomatic decrease in global left ventricular longitudinal strain \>15% after 12 months; or 5. asymptomatic increase in biomarkers (troponin I \> upper reference limit (99th centile) and increase of at least 30% from pre-treatment concentration or NTproBNP \> 125 pg/ml and increase of at least 30% from baseline) after 12 months.

Time frame: 12 months

Secondary Outcomes

Secondary efficacy composite endpoint (cancer therapeutics related cardiac dysfunction) at 6 months.

Incidence of cancer therapeutics related cardiac dysfunction defined as: 1. emergence of heart failure symptoms (NYHA class I-IV) due to impaired cardiac function or structure at 6 months; or 2. decrease LVEF \> 10% after 6 months; or 3. decrease LVEF \< 10% but to a value of 40-49% after 6 months; or 4. a decrease in global longitudinal strain of \> 15% after 6 months; or 5. asymptomatic increase in biomarkers (troponin I \> upper reference limit (99th centile) and an increase of at least 30% from pre-treatment concentration or NTproBNP \>125pg/ml and an increase of at least 30% from baseline) after 6 months.

Time frame: 6 months

Change in left ventricular ejection fraction at 6 and 12 months.

Assessed by transthoracic echocardiography.

Time frame: 6 and 12 months

Change in left ventricular diastolic function at 6 and 12 months.

Assessed as the ratio of E/E', i.e. maximum mitral annular inflow velocity during the rapid ventricular filling phase, to maximum mitral annular motion velocity by tissue Doppler during the rapid ventricular filling phase.

Central Contacts

Bartosz Krakowiak, PhD, MD

CONTACT

+48 261 660 234 bkrakowiak@4wsk.pl

Data from ClinicalTrials.gov

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