Table 2.

Ongoing randomized clinical trials addressing cardiotoxic effects of GnRH agonists vs. antagonists

Study name/trial number	Comparison groups	No. (pts.)	Inclusion criteria	Exclusion criteria	Follow-up duration	Outcome measures	Expected DoC
PRONOUNCE/NCT02663908	Degarelixa (GnRH antagonist) versus leuprolide (GnRH agonist)	545	- Men with advanced PCA - With pre-existing atherosclerotic CVD - Who have indications to start ADT	- Previous or current hormonal therapy for PCA - Acute cardiovascular disease in the previous 30 days	Up to 336 days	Primary end point is time from randomization to the first confirmed occurrence of MACE. (as death due to any cause, or non-fatal MI, or no-fatal stroke)	April 2021
NCT04182594	Degarelix + docetaxel, or one of the novelb hormonal agents versus GnRH agonist + docetaxel, or one of the novel hormonal agents	80	- Men age < 90 y/o with locally advanced or metastatic PCA, and pre-existing CVD, or CVA, or PAD or two or more major CV risk factors - Who are scheduled to receive primary ADT for 1 year, and a second line chemotherapy with docetaxel or one of the novel hormonal agents - Life expectancy of 1 year and WHO performance status of 0–2	- Prior use of ADT in past 6 months prior to randomization - Known allergic reaction to degarelix - Any situation potentially hampering compliance with the study protocol and follow-up schedule	1 year	Primary end point is time to first composite MACE (death due to any cause, MI, TIA, Cardiac ED visits, or heart catheterizations).	January 2023
PEGASUSc/NCT02799706	Degarelix + EBRT versus GnRH agonists + EBRT	885	- Men age < 80 y/o with high-risk localized or locally advanced prostate cancer scheduled to receive ADT and EBRT - Testosterone level > 200 ng/dl - Creatinine clearance > 50 ml/min - WHO performance 0–1	- Prior use of ADT - Hx of severe asthma, GI ds that interferes with drug absorption, pituitary or adrenal dysfunction, uncontrolled DM, severe liver ds, uncontrolled HTN, MI or arterial thrombotic event in the past 6 months, severe or unstable angina, NYHA class III/IV CHF or EF < 50% at baseline, PCI or multivessel CABG, carotid artery or iliofemoral artery revascularization within the last 30 days - Prior hx of malignancies other than skin cancers unless in remission for > 3 yrs - Family history of a long QT syndrome or QTc > 450 ms at baseline	Minimum of 18 months	dSecondary end point is the incidence of clinical cardiovascular events including arterial embolic or thrombotic events including CVA, MI, and other ischemic heart disease in those with prior CV events, and those without history of such events.	September 2024
	EBRT: total of 78–80 Gy (5× per wk)

Abbreviations: ADT, androgen deprivation therapy; CABG, coronary artery bypass graft; CHF, congestive heart failure; CV, cardiovascular; CVA, cerebrovascular accident; CVD, cardiovascular disease; DM, diabetes; DoC, date of completion; DS, disease or disorder; EBRT, external beam radiation therapy; ED, emergency department; EF, ejection fraction; HTN, hypertension; GI, gastro-intestinal; GnRH, gonadotropin releasing hormone; HTNL, hypertension; MACE, major cardiovascular adverse events; MI, myocardial infarction; No., number; NYHA, New York Hear Association; PAD, peripheral arterial disease; PCA, prostatic cancer; Pts, patients; TIA, transient ischemic attacks

^aDose of degarelix for all the above three studies is loading dose of 240 mg subcutaneous on day 1, followed by 80 mg monthly for the remainder of the study period

^bThe three novel anti-androgenic hormonal agents are abiraterone, enzalutamide, and apalutamide

^cThis is a joint study of the European Organization for Research and Treatment of Cancer (EORTC) Radiation Oncology Group (ROG) and Genitourinary Cancer Group (GUCG)

^dThe primary endpoint of this study is progression free survival defined as the time in days from randomization to death, clinical or biochemical progression, whichever comes first