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

December 2, 2024 updated by: 4th Military Clinical Hospital with Polyclinic, Poland

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed 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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
188

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Bartosz Krakowiak, PhD, MD
  • Phone Number: +48 261 660 234
  • Email: bkrakowiak@4wsk.pl

Study Locations

  • Poland
    • Dolnośląskie
      • Wrocław, Dolnośląskie, Poland, 50-981
        • Recruiting
        • 4th Military Clinical Hospital with Polyclinic
        • Contact:
      • Wrocław, Dolnośląskie, Poland, 53-413
        • Recruiting
        • Lower Silesian Centre for Oncology, Lung Diseases and Hematology
        • Contact:
          • Rafał Matkowski, PhD, MD
    • Mazowieckie
      • Warsaw, Mazowieckie, Poland, 04-141
        • Recruiting
        • Military Medical Institute
        • Contact:
          • Paweł Krzesiński, PhD, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Dapagliflozin
Dapagliflozin 10 mg tablet orally once daily for 12 months
Drug: Dapagliflozin
10 mg tablet q.d
Other Names:
  • Forxiga
  • Farxiga
Placebo Comparator: Placebo
Placebo tablet matching dapagliflozin orally once daily for 12 months
Drug: Placebo
tablet matching dapagliflozin 10 mg q.d

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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:

  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.
12 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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:

  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.
6 months
Change in left ventricular ejection fraction at 6 and 12 months.
Time Frame: 6 and 12 months
Assessed by transthoracic echocardiography.
6 and 12 months
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.
6 and 12 months
Change in Troponin I after 6 and 12 months.
Time Frame: 6 and 12 months
Secondary.
6 and 12 months
Change in NTproBNP levels at 6 and 12 months.
Time Frame: 6 and 12 months
Secondary.
6 and 12 months
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.
6 and 12 months
Occurrence of death from any cause.
Time Frame: 13 months (additional 1 month of safety follow-up after end of treatment).
Secondary safety endpoint.
13 months (additional 1 month of safety follow-up after end of treatment).
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.
13 months (additional 1 month of safety follow-up after end of treatment).
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.
13 months (additional 1 month of safety follow-up after end of treatment).
Occurrence of non-fatal myocardial infarction.
Time Frame: 13 months (additional 1 month of safety follow-up after end of treatment).
Secondary safety endpoint.
13 months (additional 1 month of safety follow-up after end of treatment).
Occurrence of non-fatal stroke.
Time Frame: 13 months (additional 1 month of safety follow-up after end of treatment).
Secondary safety endpoint.
13 months (additional 1 month of safety follow-up after end of treatment).
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 months (additional 1 month of safety follow-up after end of treatment).
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
13 months (additional 1 month of safety follow-up after end of treatment).
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
13 months (additional 1 month of safety follow-up after end of treatment).
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).
13 months (additional 1 month of safety follow-up after end of treatment).
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).
13 months (additional 1 month of safety follow-up after end of treatment).
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).
13 months (additional 1 month of safety follow-up after end of treatment).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
4th Military Clinical Hospital with Polyclinic, Poland

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Waldemar Banasiak, PhD, MD, 4th Military Clinical Hospital with Polyclinic

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 15, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 9, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 8, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 12, 2024

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 4, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 2, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2022/ABM/01/00039
  • 2023-506631-15-00 (Other Identifier: EUCT)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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