Prevention of Cardiac Dysfunction During Breast Cancer Therapy

Heart Failure Clinical Trial

— PRADAII  

Official title:

PRevention of cArdiac Dysfunction During Adjuvant Breast Cancer Therapy: A Randomized, Placebo-controlled, Multicenter Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03760588
• Other study ID #: 2017-004909-41
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: January 14, 2019
• Est. completion date: September 14, 2025

Study information

• Verified date: January 2023
• Source: University Hospital, Akershus
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Breast cancer is the most common cancer among women. The modern post-surgery treatment with chemotherapy, immunotherapy, radiation and hormone therapy has improved the overall 5-years survival drastically. However, an unwanted effect of the post-surgery treatment is its potentially deleterious effect on the heart resulting in cardiac dysfunction. Angiotensin antagonists are used as part of the heart failure treatment. In smaller studies angiotensin antagonists have shown to have a cardioprotective effect during breast cancer treatment. Sacubitril/valsartan is a potent drug that in addition to an angiotensin antagonist contains a neprilysin inhibitor. Sacubitril/valsartan has proved to be superior to enalapril in chronic heart failure. In this randomized placebo controlled double blind trial we hypothesize that sacubitril/valsartan used concomitantly during anthracycline containing chemotherapy for breast cancer treatment prevents cardiac dysfunction as measured by cardiac magnetic resonance imaging (CMR). PRADA II is a Norwegian multicenter trial intending to recruit 214 patients and follow them for 18 months with CMR, cardiac ultrasound, blood samples, functional capacity tests and health related quality of life questionnaires.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 214
• Est. completion date: September 14, 2025
• Est. primary completion date: September 14, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Women with histological evidence of invasive early breast cancer scheduled for adjuvant therapy with anti-cancer regimens that include anthracyclines
• Eastern Cooperative Oncology Group performance status 0-1
• Sinus rhythm

Exclusion criteria:

• Age <18 years
• Renal failure, i.e. serum creatinine greater than 133 mol/L (1.5mg/dL) or estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73m2
• Hyperkalemia, i.e. serum potassium greater than 5.0 mmol/L
• Systolic blood pressure < 100 mgHg
• Uncontrolled hypertension
• Acute myocardial infarction within the last three months
• Contraindication to ACEI or ARB or sacubitril/valsartan, including previous hypersensitivity reaction, angioedema and renal artery stenosis
• ACEI, ARB, aldosterone antagonist or sacubitril/valsartan use within 4 weeks of study start
• Clear indication for ACEI, ARB, aldosterone antagonist or sacubitril/valsartan therapy, including symptomatic heart failure
• History of hemodynamically significant valvular disease
• Active liver disease, i.e. alanine aminotransferase or aspartate aminotransferase greater than 1.5 times the upper limit of normal
• Participation in another pharmaceutical clinical trial of an investigational medicinal product (IMP) less than 4 weeks prior to inclusion or use of other investigational drugs within 5 halflives of enrollment, whichever is longer
• Conditions that would affect the participants to comply with the study protocol as psychiatric or mental disorders, alcohol abuse or other substance abuse, suspected poor drug compliance, language barriers or other factors
• Contraindication or inability to undergo CMR examination
• Fertile women with inadequate birth control, pregnancy, and/or breastfeeding. Adequate contraception includes oral, injected or implanted hormonal methods of contraception, placement of an intrauterine device or system, vasectomized partner or sexual abstinence. Fertile women are defined as following menarche and until becoming postmenopausal unless permanently sterile. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause
• Life expectancy < 12 months

Related Conditions & MeSH terms

• Breast Cancer Female
• Breast Neoplasms
• Heart Failure

Intervention

Drug:
• Sacubitril/valsartan
Target dose 97/103 mg b.i.d .

Locations

Country	Name	City	State
Norway	Akershus University Hospital	Lørenskog
Norway	Stavanger University Hospital	Stavanger
Norway	University of North Norway	Tromsø
Norway	St Olavs Hospital	Trondheim

Sponsors (9)

Lead Sponsor	Collaborator
Torbjorn Omland	Helse Stavanger HF, Klinbeforsk, Norwegian Cancer Society, Novartis, Oslo University Hospital, St. Olavs Hospital, University Hospital of North Norway, University Hospital, Akershus

Country where clinical trial is conducted

Norway, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Incidence of adverse events and serious adverse events		From randomization to end of blinded therapy (18 months)
Primary	Change in left ventricular ejection fraction by cardiovascular magnetic resonance		From randomization to end of blinded therapy (18 months)
Secondary	Change in left ventricular ejection fraction by echocardiography		From randomization to end of blinded therapy (18 months)
Secondary	Change in left ventricular systolic global longitudinal strain by echocardiography		From randomization to end of blinded therapy (18 months)
Secondary	Change in left ventricular systolic global longitudinal strain by cardiovascular magnetic resonance (CMR)		From randomization to end of blinded therapy (18 months)
Secondary	Change in left ventricular end-systolic volume measured by CMR		From randomization to end of blinded therapy (18 months)
Secondary	Incidence of a significant reduction in left ventricular systolic function measured by CMR or echocardiography	An absolute reduction in LVEF = 5% by CMR or a relative percentage reduction of global longitudinal strain (GLS) > 15%	From randomization to end of blinded therapy (18 months)
Secondary	Incidence of cardiotoxicity measured by CMR or echocardiography	Absolute reduction in LVEF = 10% to a value below 50% as measured either by CMR or Echocardiography, or incidence of clinical heart failure	From randomization to end of blinded therapy (18 months)
Secondary	Change in circulating cardiac biomarkers	Cardiac biomarkers defined as cardiac troponins I and T measured by high sensitivity assays (hs-TnI and hs-TnT) and N-terminal proB-type natriuretic peptide (NT-proBNP)	From randomization to end of blinded therapy (18 months)