Prevention of Cardiac Dysfunction During Breast Cancer Therapy
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.
Timeline
- Start
- 2019-01-31
- Primary completion
- 2024-09-05
- Completion
- 2024-09-05
Outcome
Missed primary endpoint
paper The between-group difference was 1.1 percentage points (95% CI, -0.4 to 2.7; P=0.16). PMID 40884047 ↗
paper not significantly attenuated by sacubitril/valsartan. PMID 40884047 ↗
Publications
- Omland T, Heck SL, Holte E, Lilleaasen AM, Gynnild MN, Fagerland MW, Vinje-Jakobsen V, Naes AL, Blix ES, Larsen AI, Geisler J, Gulati G, Wethal T. Sacubitril/Valsartan and Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy: The PRADA II Randomized Clinical Trial. Circulation. 2025 Oct 21;152(16):1136-1145. doi: 10.1161/CIRCULATIONAHA.125.076616. Epub 2025 Aug 29.
- Mecinaj A, Gulati G, Heck SL, Holte E, Fagerland MW, Larsen AI, Blix ES, Geisler J, Wethal T, Omland T. Rationale and design of the PRevention of cArdiac Dysfunction during Adjuvant breast cancer therapy (PRADA II) trial: a randomized, placebo-controlled, multicenter trial. Cardiooncology. 2021 Sep 27;7(1):33. doi: 10.1186/s40959-021-00115-w.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Sacubitril/valsartan | Unknown | 97 mg | Oral |
| Subject | Sacubitril/valsartan | Unknown | 103 mg | Oral |