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

Breast Cancer Clinical Trial

— PROTECTAA  

Official title:

A Multicentre, Randomised, Double-blind, Placebo-controlled Phase III Study, Evaluating the Effect of Dapagliflozin on Prevention of Cardiotoxicity in Breast Cancer Patients Undergoing Anthracycline-based Chemotherapy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06304857
• Other study ID #: 2022/ABM/01/00039
• Secondary ID: 2023-506631-15-0
• Status: Recruiting
• Phase: Phase 3
• Start date: April 15, 2024
• Est. completion date: December 31, 2027

Study information

• Verified date: April 2024
• Source: 4th Military Clinical Hospital with Polyclinic, Poland
• Contact: Bartosz Krakowiak, PhD, MD
• Phone: +48 261 660 234
• Email: bkrakowiak[@]4wsk.pl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 188
• Est. completion date: December 31, 2027
• Est. primary completion date: December 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Heart Failure

Intervention

Drug:
• Dapagliflozin
10 mg tablet q.d
• Placebo
tablet matching dapagliflozin 10 mg q.d

Locations

Country	Name	City	State
Poland	Military Medical Institute	Warsaw	Mazowieckie
Poland	4th Military Clinical Hospital with Polyclinic	Wroclaw	Dolnoslaskie
Poland	Lower Silesian Centre for Oncology, Lung Diseases and Hematology	Wroclaw	Dolnoslaskie

Sponsors (1)

Lead Sponsor	Collaborator
4th Military Clinical Hospital with Polyclinic, Poland

Country where clinical trial is conducted

Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Primary efficacy composite endpoint (cancer therapeutics related cardiac dysfunction) at 12 months.	Incidence of cancer therapeutics related cardiac dysfunction defined as: the appearance of heart failure symptoms (NYHA class I-IV) due to an impairment of heart function or structure within 12 months; or; asymptomatic decrease in left ventricular ejection fraction > 10% after 12 months; or; asymptomatic decrease in left ventricular ejection fraction < 10% but up to 40-49% after 12 months; or; asymptomatic decrease in global left ventricular longitudinal strain >15% after 12 months; or; 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.	12 months
Secondary	Secondary efficacy composite endpoint (cancer therapeutics related cardiac dysfunction) at 6 months.	Incidence of cancer therapeutics related cardiac dysfunction defined as: emergence of heart failure symptoms (NYHA class I-IV) due to impaired cardiac function or structure at 6 months; or; decrease LVEF > 10% after 6 months; or; decrease LVEF < 10% but to a value of 40-49% after 6 months; or; a decrease in global longitudinal strain of > 15% after 6 months; or; 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.	6 months
Secondary	Change in left ventricular ejection fraction at 6 and 12 months.	Assessed by transthoracic echocardiography.	6 and 12 months
Secondary	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.	6 and 12 months
Secondary	Change in Troponin I after 6 and 12 months.	Secondary.	6 and 12 months
Secondary	Change in NTproBNP levels at 6 and 12 months.	Secondary.	6 and 12 months
Secondary	Quality of life at 6 and 12 months assessed using the five-dimensional EQ-5D questionnaire.	The EQ-5D questionnaire consists of two parts: descriptive one, which measures five dimensions of health (mobility, self care, usual activities, pain & discomfort, anxiety & depression) and EQ Visual Analogue Scale numbered from 0 to 100, where higher value indicate better self-reported health.	6 and 12 months
Secondary	Occurrence of death from any cause.	Secondary safety endpoint.	13 months (additional 1 month of safety follow-up after end of treatment).
Secondary	Composite endpoint of cardiovascular events.	Secondary safety endpoint. Occurrence of death from cardiovascular causes, nonfatal myocardial infarction, non-fatal stroke.	13 months (additional 1 month of safety follow-up after end of treatment).
Secondary	Occurrence of death from any cardiovascular reasons.	Secondary safety endpoint.	13 months (additional 1 month of safety follow-up after end of treatment).
Secondary	Occurrence of non-fatal myocardial infarction.	Secondary safety endpoint.	13 months (additional 1 month of safety follow-up after end of treatment).
Secondary	Occurrence of non-fatal stroke.	Secondary safety endpoint.	13 months (additional 1 month of safety follow-up after end of treatment).
Secondary	Occurrence of hypoglycaemia.	Secondary safety endpoint. Hypoglycaemia is defined as serum glucose level 3 mmol/l (<54 mg/dl) with coexisting related clinical symptoms.	13 months (additional 1 month of safety follow-up after end of treatment).
Secondary	Occurrence of ionic disorders.	Secondary safety endpoint, defined as occurrence of: Sodium plasma level of >150 mmol/L; Potassium plasma level of >6.0 mmol/L	13 months (additional 1 month of safety follow-up after end of treatment).
Secondary	Occurrence of renal failure.	Secondary safety endpoint. Defined as: sustained (i.e. >28 days) decline in eGFR =50% AND/OR; reaching end stage renal disease defined as: sustained (i.e. >28 days) eGFR <15 mL/min/1.73 m2; chronic dialysis treatment; receiving a renal transplant AND/OR; renal death	13 months (additional 1 month of safety follow-up after end of treatment).
Secondary	Occurrence of hypersensitivity to investigated drug.	Secondary safety endpoint. Any unexpected adverse drug reaction (UADR).	13 months (additional 1 month of safety follow-up after end of treatment).
Secondary	Occurrence of allergic reactions.	Secondary safety endpoint. Any hypersensitivity reaction with proven immunological pathomechanism (types I-IV according to Coombs and Gell).	13 months (additional 1 month of safety follow-up after end of treatment).
Secondary	Occurrence of infection.	Secondary safety endpoint. Any symptomatic infection (viral, bacterial or fungal).	13 months (additional 1 month of safety follow-up after end of treatment).