title: Rationale and design of the prevention of cardiac dysfunction during an Adjuvant Breast Cancer Therapy (PRADA) Trial.
abstract: OBJECTIVE
  The PRevention of cArdiac Dysfunction during Adjuvant breast cancer therapy (PRADA) study is a randomized, placebo-controlled, double-blind trial to determine whether angiotensin receptor blockers (ARB), or beta-blockers or their combination may prevent the development of left ventricular (LV) dysfunction in patients on standard adjuvant treatment for early breast cancer.
  
  
  METHODS
  Following surgical resection, 120 breast cancer patients scheduled for adjuvant epirubicin-containing chemotherapy and, if indicated, trastuzumab, will be included. They will be randomized to an ARB (candesartan), a beta-blocker (metoprolol) and matching placebos in a 2 × 2 factorial design. The primary objective of the PRADA study is to assess whether prophylactic ARB and/or beta-blockers may prevent a reduction in LV ejection fraction (EF) after adjuvant treatment of early breast cancer, as evaluated by serial cardiovascular magnetic resonance (CMR) performed at randomization, after the first chemotherapy cycle and on its completion, and for subgroups, on completion of radiotherapy or trastuzumab. Secondary outcome measures include echocardiographic indices of LV diastolic dysfunction, structural myocardial alterations assessed by CMR and changes in cardiac biomarkers.
  
  
  CONCLUSIONS
  PRADA may provide new information on the prophylactic effect of ARB and beta-blockers in patients with early breast cancer regarding the risk of developing cardiac dysfunction from adjuvant cancer treatment.
authors.affiliation: Department of Radiology, Division of Diagnostics and Technology, Akershus University Hospital and University of Oslo, Oslo, Norway.
authors.forename: Siri Lagethon
authors.initials: SL
authors.lastname: Heck
authors.forename: Geeta
authors.initials: G
authors.lastname: Gulati
authors.forename: Anne Hansen
authors.initials: AH
authors.lastname: Ree
authors.forename: Jeanette
authors.initials: J
authors.lastname: Schulz-Menger
authors.forename: Berit
authors.initials: B
authors.lastname: Gravdehaug
authors.forename: Helge
authors.initials: H
authors.lastname: Røsjø
authors.forename: Kjetil
authors.initials: K
authors.lastname: Steine
authors.forename: Ase
authors.initials: A
authors.lastname: Bratland
authors.forename: Pavel
authors.initials: P
authors.lastname: Hoffmann
authors.forename: Jürgen
authors.initials: J
authors.lastname: Geisler
authors.forename: Torbjørn
authors.initials: T
authors.lastname: Omland
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood; D001943:Breast Neoplasms / Q000188:drug therapy*; D003971:Diastole / Q000187:drug effects; D004311:Double-Blind Method; D004452:Echocardiography; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D006801:Humans; D008279:Magnetic Resonance Imaging; D011897:Random Allocation; D013223:Statistics as Topic; D013599:Systole / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D000319:Adrenergic beta-Antagonists; D057911:Angiotensin Receptor Antagonists; D000970:Antineoplastic Agents; D015415:Biomarkers