NCT04182594.

Study name	A phase‐II, randomised, assessor‐blind, controlled trial comparing the occurrence of cardiovascular events in patients with prostate cancer and cardiovascular risk factors receiving degarelix or GnRH agonist
Methods	Study design: randomized phase II, open‐label superiority study of the use of androgen suppression therapy combined with second‐line hormonal or chemotherapy in men with advanced prostate cancer and pre‐existing cardiovascular risks Setting: Rabin Medical Center ‐ Beilinson Hospital Country: Israel Follow‐up: 1 year
Participants	Inclusion criteria: Locally advanced high‐risk prostate cancer OR metastatic prostate cancer patients Patients are scheduled to receive a combination of either: primary androgen suppression therapy for 12 months + either chemotherapy with docetaxel; OR primary androgen suppression therapy for 12 months + second‐line hormonal treatment with abiraterone/enzalutamide/apalutamide. Patients with a medical history of either of the following: Myocardial infarction; Ischemic or hemorrhagic cerebrovascular conditions; Arterial embolic and thrombotic events; Ischemic heart disease; Prior coronary artery or iliofemoral artery revascularization (percutaneous or surgical procedures); Peripheral vascular disease (e.g. significant stenosis (ABPI < 0.9), claudication, prior vascular surgery/intervention); 2 out of 3 cardiovascular risk factors: hypertension, diabetes, current smoking. Patients age 18 to 90 years Life expectancy of over 12 months WHO performance status of 0 to 2 Individual is able and has agreed to sign a consent form Exclusion criteria: Prior use of androgen suppression therapy in past 6 months prior to randomization. We will, however, allow prior use of antiandrogens such as bicalutamide (Casodex), flutamide (Chimax, Drogenil), and cyproterone (Cyprostat). Known allergic reaction to degarelix Any psychological, familial, sociological, or geographical situation potentially hampering compliance with the study protocol and follow‐up schedule Target sample size: 80
Interventions	Group 1: degarelix Group 2: GnRH agonist
Outcomes	Primary outcome: Time to first cardiovascular event Secondary outcomes: Time to first MACCE event Cardiac echocardiography Hormonal profile NTproBNP levels Adverse events PSA levels BMI Quality of life: FACT‐P questionnaire Glucose profile Cholesterol levels
Starting date	17 January 2020
Contact information	Rabin Medical Center ‐ Beilinson Hospital Yaara Ber, PhD 972‐3‐9376553 yaaraba1@clalit.org.il
Notes	Sponsor: Rabin Medical Center and Ferring Pharmaceuticals Recruitment status: not yet recruiting (checked on 4 November 2020) Estimated primary completion date: 17 January 2023 Trial ID: NCT04182594

BMI: body mass index

FACT‐P: Functional Assessment of Cancer Therapy‐Prostate

GnRH: gonadotropin‐releasing hormone

PSA: prostate‐specific antigen

s.c.: subcutaneous

WHO: World Health Organization

CAB: complete androgen blockade

TURP: transurethral resection of the prostate

PTEN: Phosphatase and tensin homolog

MRI: Magnetic resonance imaging

ICH/GCP: International Conference on Harmonisation of technical requirements for registration of pharmaceuticals for human use/ Good Clinical Practice

AST: aspartate transaminase

ALT: alanine transaminase

PCI: percutaneous coronary intervention

CABG: coronary artery bypass grafting
BP: blood pressure

CTCAE: common terminology criteria for adverse events

ABPI: ankle brachial pressure index

MACCE: major adverse cardiac and cerebrovascular events

NTproBNP: N terminales pro brain natriuretic peptide