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NCT Number: NCT06304857

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

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.

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Key information

Conditions

Breast Cancer Breast Diseases Breast Neoplasms Cardiovascular Diseases Heart Diseases Heart Failure Neoplasms Neoplasms by Site Skin Diseases Skin and Connective Tissue Diseases

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

4th Military Clinical Hospital with Polyclinic, Wroclaw, Lower Silesian Voivodeship, Poland

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Dapagliflozin

Drug

10 mg tablet q.d

Other names: Farxiga, Forxiga

Placebo

Drug

tablet matching dapagliflozin 10 mg q.d

Primary outcomes

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

    Time frame: 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.

Secondary outcomes

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

    Time frame: 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.

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

    Time frame: 6 and 12 months

    Assessed by transthoracic echocardiography.

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

    Time frame: 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.

  4. Change in Troponin I after 6 and 12 months.

    Time frame: 6 and 12 months

    Secondary.

  5. Change in NTproBNP levels at 6 and 12 months.

    Time frame: 6 and 12 months

    Secondary.

  6. Quality of life at 6 and 12 months assessed using the five-dimensional EQ-5D questionnaire.

    Time frame: 6 and 12 months

    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.

  7. Occurrence of death from any cause.

    Time frame: 13 months (additional 1 month of safety follow-up after end of treatment).

    Secondary safety endpoint.

  8. Composite endpoint of cardiovascular events.

    Time frame: 13 months (additional 1 month of safety follow-up after end of treatment).

    Secondary safety endpoint. Occurrence of death from cardiovascular causes, nonfatal myocardial infarction, non-fatal stroke.

  9. Occurrence of death from any cardiovascular reasons.

    Time frame: 13 months (additional 1 month of safety follow-up after end of treatment).

    Secondary safety endpoint.

  10. Occurrence of non-fatal myocardial infarction.

    Time frame: 13 months (additional 1 month of safety follow-up after end of treatment).

    Secondary safety endpoint.

  11. Occurrence of non-fatal stroke.

    Time frame: 13 months (additional 1 month of safety follow-up after end of treatment).

    Secondary safety endpoint.

  12. Occurrence of hypoglycaemia.

    Time frame: 13 months (additional 1 month of safety follow-up after end of treatment).

    Secondary safety endpoint. Hypoglycaemia is defined as serum glucose level 3 mmol/l (<54 mg/dl) with coexisting related clinical symptoms.

  13. Occurrence of ionic disorders.

    Time frame: 13 months (additional 1 month of safety follow-up after end of treatment).

    Secondary safety endpoint, defined as occurrence of:

    • Sodium plasma level of >150 mmol/L
    • Potassium plasma level of >6.0 mmol/L

  14. Occurrence of renal failure.

    Time frame: 13 months (additional 1 month of safety follow-up after end of treatment).

    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

  15. Occurrence of hypersensitivity to investigated drug.

    Time frame: 13 months (additional 1 month of safety follow-up after end of treatment).

    Secondary safety endpoint. Any unexpected adverse drug reaction (UADR).

  16. Occurrence of allergic reactions.

    Time frame: 13 months (additional 1 month of safety follow-up after end of treatment).

    Secondary safety endpoint. Any hypersensitivity reaction with proven immunological pathomechanism (types I-IV according to Coombs and Gell).

  17. Occurrence of infection.

    Time frame: 13 months (additional 1 month of safety follow-up after end of treatment).

    Secondary safety endpoint. Any symptomatic infection (viral, bacterial or fungal).

Study contacts

Contact information is provided by the study sponsor or research team.

Bartosz Krakowiak, PhD, MD

CONTACT

[email protected]

+48 261 660 234

Sponsors and collaborators

Lead sponsor

4th Military Clinical Hospital with Polyclinic, Poland

Other

Registry information

Official study 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

Acronym: PROTECTAA

Important dates

Study start
2024
Primary completion
2026
Study completion
2027
First posted
Mar 12, 2024
Registry last updated
Dec 4, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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