Back to resultsA Trial Comparing Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Advanced Prostate Cancer and Cardiovascular Disease (PRONOUNCE)
Primary Purpose
Prostate Cancer
Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Degarelix
Leuprolide
Sponsored by
About this trial
This is an interventional treatment trial for Prostate Cancer
Eligibility Criteria
Inclusion Criteria:
- Advanced prostate cancer
- Indication to initiate androgen deprivation therapy (ADT)
- Predefined cardiovascular disease
Exclusion Criteria:
- Previous or current hormonal management of prostate cancer (unless terminated at least 12 months prior to trial)
- Acute cardiovascular disease in the previous 30 days
Sites / Locations
- Urology Center of Alabama PC
- Arizona Institute of Urology
- Urological Associates of Southern Arizona
- University of Arizona College of Medicine
- Urology Associates, PA
- Pacific Cancer Medical Center, Inc.
- San Diego Clinical Trials
- Clinical Trials Research
- VA Greater Los Angeles Healthcare System
- University of California, Irvine Medical Center
- Skyline Urology
- Innovative Clinical Research Institute
- Urology Center of Colorado
- Yale University
- Urologic Surgeons of Washington
- Mount Sinai Comprehensive Cancer Center
- San Marcus Research Clinic Inc
- Clinical Research Center of Florida
- Florida Urology Partners
- Comprehensive Urologic Care
- Springfield Clinic LLP
- Urology of Indiana LLC
- First Urology PSC
- Iowa Clinic
- University of Kansas Medical Center Research Institute, Inc.
- Kansas City Urology Care
- Regional Urology, LLC
- Chesapeake Urology Associates, P.A.
- Delaware Valley Urology LLC Westhampton
- Holy Name Medical Center
- Urology Group of New Mexico PC
- Montefiore Medical Center PRIME
- Advanced Urology Centers of New York Elmont Division
- SUNY Upstate Medical University
- Duke University Medical Center
- Veterans Affairs Medical Center-Salisbury, NC
- Signal Point Clinical Research Center
- Clinical Research Solutions PC
- Urologic Consultants of Southeaster PA LLP
- Lancaster Urology
- University of Pennsylvania
- Ralph H. Johnson VA Medical Center
- Medical University of South Carolina (MUSC)
- Erlanger Health System
- Urology of Virginia
- Seattle Urology Research Center
- University of Washington School of Medicine
- Medical College of Wisconsin, Inc.
- The Male Health Centre Euroscope Inc
- J. Giddens Medicine Professional Corporation
- G. Kenneth Jansz Medicine Professional Corporation
- Urology Associates Urologic Medical Research
- London Health Sciences Centre
- Femalemale Health Centres
- Princess Margaret Cancer Centre
- Uro Laval
- Jewish General Hospital / McGill University
- CHU de Québec -Hôtel-Dieu de Québec
- Fakultni nemocnice Olomouc
- Fakultni nemocnice Ostrava
- Multiscan s.r.o.
- Urocentrum Plzen
- Fakultni nemocnice v Motole
- Proton Therapy Center Czech s.r.o.
- Oblastni nemocnice Pribram a.s.
- Krajska zdravotni a.s. - Masarykova nemocnice v Usti nad Labem o.z.
- Keski-Suomen keskussairaala
- Tampereen yliopistollinen
- Institut Sainte Catherine
- Groupe Hospitalier Pellegrin Tripode
- Hôpital Henri Mondor
- CHU de Grenoble - Hôpital Albert Michallon
- CH de Libourne- Hopital Robert Boulin
- Hopital Claude Huriez - CHU Lille
- Hopital Edouard Herriot - CHU Lyon
- Centre Hospitalier Régional Universitaire de Tours
- Hopital Bichat - Claude Bernard
- Clinique Saint Jean Languedoc
- Universitaetsklinikum Freiburg
- Urologische Gemeinschaftspraxis
- Urologische Gemeinschaftspraxis
- Staedtisches Klinikum Braunschweig GmbH - Standort Salzdahlumer
- Klinikum Oldenburg gGmbH
- Kliniken Maria Hilf GmbH
- Praxisklinik Urologie Rhein Ruhr
- Krankenhaus Martha-Maria Halle-Doelau
- Facharztpraxis für Urologie
- Staedtisches Klinikum Dresden Standort Dresden-Friedrichstadt
- Urologie am Nordplatz
- Gynaekologisches Zentrum Bonn-Friedensplatz
- Central Clinic of Athens
- General Hospital of Athens "Alexandra"
- T.Y.P.E.T. Hygeias Melathron Hospital
- University General Hospital of Heraklion
- University of Patras Medical School
- General Hospital Papageorgiou
- Swietokrzyskie Centrum Onkologii
- Provita Profamilia
- WroMedica
- DERMED Centrum Medyczne Sp. z o.o.
- SBHI of Sverdiovsk Region "Sverdiovsk Regional Clinical Hospital #1
- City Clinical Hospital n.a. Botkin
- FSBI "Moscow scientific research oncology institute"
- FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin"
- SBEI HPE "Moscow State Medical and Dentistry University n.a. A. I. Evdokimov"
- FBHI Privolzhskiy District Medical Centre FMBA of Russia
- Medical Center Avitsenna
- BHI of Omsk region "Clinical Oncology Dispensary
- FFSBI "The Nikiforov Russian Center of Emergency and Radiation Medicine"
- CUIMED s.r.o.
- Urocentrum Bratislava s.r.o.
- Vychodoslovensky onkologicky ustav, a.s.
- Nemocnica Kosice-Saca, a.s.
- Zeleznicna nemocnica Kosice
- UROCENTRUM LEVICE s.r.o.
- UROAMB s.r.o.
- Univerzitna nemocnica Martin
- Fakultna nemocnica Nitra
- UROEXAM, spol. s r.o.
- MILAB s.r.o.
- MIRAMED s.r.o
- UROCENTRUM SALA s.r.o.
- Privatna Urologicka ambulancia
- Fakultna nemocnica s poliklinikou Zilina
- Groote Schuur Hospital Department of Urology
- Prince Philip Hospital
- Charing Cross Hospital
- Scunthorpe General Hospital
- St Peter's Hospital
- Royal Hallamshire Hospital
- Addenbrooke's Hospital
- Royal Devon and Exeter Hospital (Wonford)
- Salford Royal
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Degarelix
Leuprolide
Arm Description
Outcomes
Primary Outcome Measures
Time From Randomization to the First Confirmed (Adjudicated) Occurrence of the Composite Major Adverse Cardiovascular Event (MACE) Endpoint; Percentage of Observed Subjects With Outcome Measure Events During the Trial
Composite MACE endpoint was defined as: death due to any cause, non-fatal myocardial infarction or non-fatal stroke.
Kaplan Meier plots of the cumulative incidence rate by treatment groups were used to depict first confirmed (adjudicated) occurrence of composite MACE over time. Percentage of observed subjects with outcome measure events during the trial are reported.
Subjects were censored at the time a subject discontinued the trial, was lost to follow-up, discontinued treatment with IMP, initiated treatment with prohibited medication (including hormonal combination therapy), or at Day 336, whichever occurred first.
Secondary Outcome Measures
Time From Randomization to the First Confirmed (Adjudicated) Occurrence of Cardiovascular (CV)-Related Death, Non-fatal Myocardial Infarction or Non-fatal Stroke; Percentage of Observed Subjects With Outcome Measure Events During the Trial
Kaplan Meier plots of the cumulative incidence rate by treatment groups were used to depict confirmed (adjudicated) occurrence of CV-related death, non-fatal myocardial infarction or non-fatal stroke. Percentage of observed subjects with outcome measure events during the trial are reported.
Subjects were censored at the time a subject discontinued the trial, was lost to follow-up, discontinued treatment with IMP, initiated treatment with prohibited medication (including hormonal combination therapy), or at Day 336, whichever occurred first.
Time From Randomization to Confirmed (Adjudicated) CV-related Death; Percentage of Observed Subjects With Outcome Measure Events During the Trial
Kaplan Meier plots of the cumulative incidence rate by treatment groups were used to depict confirmed (adjudicated) CV-related death. Percentage of observed subjects with outcome measure events during the trial are reported. Percentage of observed subjects with outcome measure events during the trial are reported.
Subjects were censored at the time a subject discontinued the trial, was lost to follow-up, discontinued treatment with IMP, initiated treatment with prohibited medication (including hormonal combination therapy), or at Day 336, whichever occurred first.
Time From Randomization to the First Confirmed (Adjudicated) Myocardial Infarction; Percentage of Observed Subjects With Outcome Measure Events During the Trial
Kaplan Meier plots of the cumulative incidence rate by treatment groups were used to depict first confirmed (adjudicated) myocardial infarction. Percentage of observed subjects with outcome measure events during the trial are reported.
Subjects were censored at the time a subject discontinued the trial, was lost to follow-up, discontinued treatment with IMP, initiated treatment with prohibited medication (including hormonal combination therapy), or at Day 336, whichever occurred first.
Time From Randomization to the First Confirmed (Adjudicated) Stroke; Percentage of Observed Subjects With Outcome Measure Events During the Trial
Kaplan Meier plots of the cumulative incidence rate by treatment groups were used to depict first confirmed (adjudicated) stroke. Percentage of observed subjects with outcome measure events during the trial are reported.
Subjects were censored at the time a subject discontinued the trial, was lost to follow-up, discontinued treatment with IMP, initiated treatment with prohibited medication (including hormonal combination therapy), or at Day 336, whichever occurred first.
Time From Randomization to the First Confirmed (Adjudicated) Unstable Angina Requiring Hospitalization; Percentage of Observed Subjects With Outcome Measure Events During the Trial
Kaplan Meier plots of the cumulative incidence rate by treatment groups were used to depict first confirmed (adjudicated) unstable angina requiring hospitalization. Percentage of observed subjects with outcome measure events during the trial are reported.
Subjects were censored at the time a subject discontinued the trial, was lost to follow-up, discontinued treatment with IMP, initiated treatment with prohibited medication (including hormonal combination therapy), or at Day 336, whichever occurred first.
Time From Randomization to Death Due to Any Cause; Percentage of Observed Subjects With Outcome Measure Events During the Trial
Kaplan Meier plots of the cumulative incidence rate by treatment groups were used to depict death due to any cause. Percentage of observed subjects with outcome measure events during the trial are reported.
Subjects were censored at the time a subject discontinued the trial, was lost to follow-up, discontinued treatment with IMP, initiated treatment with prohibited medication (including hormonal combination therapy), or at Day 336, whichever occurred first.
Testosterone Levels at Days 28, 168 and 336 in the Degarelix and Leuprolide Treatment Groups
Median levels and interquartile ranges for serum testosterone at Days 28, 168, and 336 are presented.
Time From Randomization to Failure in Progression-free Survival (PFS); Percentage of Observed Subjects With Outcome Measure Events During the Trial
Time to failure in PFS was defined as the time, measured in days, from randomization to the first occurrence of either death, radiographic disease progression, introduction of additional prostate cancer therapies for progression, or PSA failure.
Subjects who discontinued treatment with IMP or withdrew from the trial were censored at the time of discontinuation/withdrawal.
Kaplan Meier plots of the cumulative incidence rate by treatment groups were used to depict failure in PFS. Percentage of observed subjects with outcome measure events during the trial are reported.
Changes From Baseline in International Prostate Symptom Score (IPSS) Total and Quality of Life (QoL) Scores
Lower urinary tract symptoms were measured with the IPSS Version 1 (IPSS-1). The IPSS is a subject-administered questionnaire containing seven items to evaluate symptoms of urinary obstruction (incomplete emptying, frequency, intermittency, urgency, weak stream, straining, nocturia) over the preceding week. Each urinary symptom question was assigned points from 0 to 5 indicating increasing severity of the particular symptom. The total IPSS-1 score was then calculated as summation over the responses for all 7 questions. The total IPSS-1 score was transformed to a scale from 0 (lowest score) to 100 (highest score). Higher scores reflect higher severity of symptoms. The IPSS-1 included an additional single question to assess a subject's QoL in relation to his urinary symptoms; response to this question was analyzed separately and was not included in the total IPSS score. The score was similarly scaled from 0 to 100.
Change from baseline in IPSS Total and QoL scores are presented.
Total Number of CV-related Hospitalization Events Over the Duration of the Trial
The total number of CV-related hospitalizations over the duration of the trial was defined as the number of hospitalizations due to CV-related adverse events, observed from the first exposure to IMP up until Day 336 for each subject.
Total Number of Coronary Artery By-pass Grafting (CABG) or Percutaneous Coronary Intervention (PCI) Procedures Over the Duration of the Trial
The total number of CABG or PCI procedures observed for each subject over the duration of the trial
Total Number of CV-related Emergency Room (ER) Visit Events Over the Duration of the Trial
CV-related ER visit events (that did not lead to hospitalization) was observed from the first exposure to IMP up until Day 336 for each subject.
Change in Utility, Based on EuroQol Group 5 Dimensions 5 Levels Questionnaire (EQ-5D-5L)
The EQ-5D-5L essentially consists of 2 systems - the EQ-5D-5L descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-5L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The EQ VAS is an overall estimation of the present health status. The results from the EQ-5D-5L questionnaire were converted into quality adjusted life year (QALY) units.
The QALY is estimated by combining the value of life (utility value) and length of life. Quality adjusted life years are based on a principle assuming that a year of life lived in perfect health is worth 1 QALY and that a year of life lived in a state of less than perfect health is worth less than 1.
Changes From Baseline in Duke Activity Status Index (DASI) Global Score
The DASI is a self-administered instrument developed to measure functional capacity in subjects with cardiovascular disease (CVD). It contains 12 items referring to the present time, assessing the ability to perform physical tasks in five domains: personal care (1 item), ambulation (4 items), household tasks (4 items), sexual function (1 item) and recreation (2 items). Each question was answered by one of four options: 'yes with no difficulty' / 'yes, but with some difficulty' / 'no, I can't do this' / 'don't do this for other reasons'. A global score was calculated with a higher score indicating a higher functional capacity. The minimum score is 0 and the maximum score is 58.2 points.
Change from baseline in DASI Global score is presented.
Changes From Baseline in Cardiac Anxiety Questionnaire (CAQ) Global Score and Score Per Domain
The CAQ is a self-administered questionnaire developed to measure heart-focused anxiety in persons with or without heart disease. It contains 18 items referring to the present time assessing cardiac anxiety in three domains: fear (8 items, each item could be scored between 0 "never" to 4 "always", maximum total score 32), avoidance (5 items, each item could be scored between 0 "never" to 4 "always", maximum total score 20) and attention (5 items, each item could be scored between 0 "never" to 4 "always", maximum total score 20). A higher score indicated greater cardiac anxiety and the total score range was between 0 and 72.
Change from baseline in CAQ Global score and score per domain are presented.
Number of Subjects With Adverse Events (AEs)
Adverse events were recorded from signed informed consent until end-of-trial. Adverse events with onset after start of IMP treatment, and within 3 months after (1 month=28 days) last dosing of IMP, were considered 'treatment-emergent' and are presented for the safety analysis set.
Intensity of AEs
The intensity of AE was graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (version 4.02) 5-point scale.
AE were categorized as grade 1 Mild (minor; no specific medical intervention; asymptomatic laboratory findings only; marginal clinical relevance), Grade 2 Moderate (minimal intervention: local intervention; non-invasive intervention), Grade 3 Severe (significant symptoms, requiring hospitalization or invasive intervention; transfusion; elective interventional radiological procedure; therapeutic endoscopy or operation), Grade 4 Life-threatening or disabling (complicated by acute, life-threatening metabolic or CV complications such as circulatory failure, hemorrhage, sepsis. Life-threatening physiologic consequences; need for intensive care or emergent invasive procedure; emergent interventional radiological procedure, therapeutic endoscopy or operation) and Grade 5 Death. Events with grades 3, 4 and 5 were categorized as severe.
Changes in Vital Signs
Number of subjects shifting from normal value(s) in vital signs (pulse and blood pressure) at baseline to clinically significant abnormal value(s) at end-of-trial are presented.
Note: Only subjects with appropriate baseline and post-baseline data are included in the evaluation.
Full Information
NCT ID
NCT02663908
First Posted
January 22, 2016
Last Updated
June 28, 2022
Sponsor
Ferring Pharmaceuticals
Collaborators
Memorial Sloan Kettering Cancer Center, Duke Clinical Research Institute
1. Study Identification
Unique Protocol Identification Number
NCT02663908
Brief Title
A Trial Comparing Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Advanced Prostate Cancer and Cardiovascular Disease
Acronym
PRONOUNCE
Official Title
A Multi-Center, Randomized, Assessor-Blind, Controlled Trial Comparing the Occurrence of Major Adverse Cardiovascular Events (MACEs) in Patients With Prostate Cancer and Cardiovascular Disease Receiving Degarelix (Gonadotropin-Releasing Hormone (GnRH) Receptor Antagonist) or Leuprolide (GnRH Receptor Agonist)
Study Type
Interventional
2. Study Status
Record Verification Date
May 2022
Overall Recruitment Status
Terminated
Why Stopped
Recruitment rate; a lower than anticipated observed cardiovascular event rate. The Sponsor decision to stop the trial was not based on any safety concerns or any knowledge of the results, or influenced by issues imposed by the COVID-19 pandemic.
Study Start Date
April 19, 2016 (Actual)
Primary Completion Date
March 29, 2021 (Actual)
Study Completion Date
March 29, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ferring Pharmaceuticals
Collaborators
Memorial Sloan Kettering Cancer Center, Duke Clinical Research Institute
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this trial is to test if a marketed drug for advanced prostate cancer (FIRMAGON) can reduce the risk of cardiovascular complications as compared to another marketed drug for advanced prostate cancer (LUPRON DEPOT) in subjects with prostate cancer and cardiovascular disease.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
545 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Degarelix
Arm Type
Experimental
Arm Title
Leuprolide
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Degarelix
Other Intervention Name(s)
FIRMAGON
Intervention Type
Drug
Intervention Name(s)
Leuprolide
Other Intervention Name(s)
LUPRON DEPOT
Primary Outcome Measure Information:
Title
Time From Randomization to the First Confirmed (Adjudicated) Occurrence of the Composite Major Adverse Cardiovascular Event (MACE) Endpoint; Percentage of Observed Subjects With Outcome Measure Events During the Trial
Description
Composite MACE endpoint was defined as: death due to any cause, non-fatal myocardial infarction or non-fatal stroke.
Kaplan Meier plots of the cumulative incidence rate by treatment groups were used to depict first confirmed (adjudicated) occurrence of composite MACE over time. Percentage of observed subjects with outcome measure events during the trial are reported.
Subjects were censored at the time a subject discontinued the trial, was lost to follow-up, discontinued treatment with IMP, initiated treatment with prohibited medication (including hormonal combination therapy), or at Day 336, whichever occurred first.
Time Frame
Randomization to Day 336 (end-of-trial)
Secondary Outcome Measure Information:
Title
Time From Randomization to the First Confirmed (Adjudicated) Occurrence of Cardiovascular (CV)-Related Death, Non-fatal Myocardial Infarction or Non-fatal Stroke; Percentage of Observed Subjects With Outcome Measure Events During the Trial
Description
Kaplan Meier plots of the cumulative incidence rate by treatment groups were used to depict confirmed (adjudicated) occurrence of CV-related death, non-fatal myocardial infarction or non-fatal stroke. Percentage of observed subjects with outcome measure events during the trial are reported.
Subjects were censored at the time a subject discontinued the trial, was lost to follow-up, discontinued treatment with IMP, initiated treatment with prohibited medication (including hormonal combination therapy), or at Day 336, whichever occurred first.
Time Frame
Randomization to Day 336 (end-of-trial)
Title
Time From Randomization to Confirmed (Adjudicated) CV-related Death; Percentage of Observed Subjects With Outcome Measure Events During the Trial
Description
Kaplan Meier plots of the cumulative incidence rate by treatment groups were used to depict confirmed (adjudicated) CV-related death. Percentage of observed subjects with outcome measure events during the trial are reported. Percentage of observed subjects with outcome measure events during the trial are reported.
Subjects were censored at the time a subject discontinued the trial, was lost to follow-up, discontinued treatment with IMP, initiated treatment with prohibited medication (including hormonal combination therapy), or at Day 336, whichever occurred first.
Time Frame
Randomization to Day 336 (end-of-trial)
Title
Time From Randomization to the First Confirmed (Adjudicated) Myocardial Infarction; Percentage of Observed Subjects With Outcome Measure Events During the Trial
Description
Kaplan Meier plots of the cumulative incidence rate by treatment groups were used to depict first confirmed (adjudicated) myocardial infarction. Percentage of observed subjects with outcome measure events during the trial are reported.
Subjects were censored at the time a subject discontinued the trial, was lost to follow-up, discontinued treatment with IMP, initiated treatment with prohibited medication (including hormonal combination therapy), or at Day 336, whichever occurred first.
Time Frame
Randomization to Day 336 (end-of-trial)
Title
Time From Randomization to the First Confirmed (Adjudicated) Stroke; Percentage of Observed Subjects With Outcome Measure Events During the Trial
Description
Kaplan Meier plots of the cumulative incidence rate by treatment groups were used to depict first confirmed (adjudicated) stroke. Percentage of observed subjects with outcome measure events during the trial are reported.
Subjects were censored at the time a subject discontinued the trial, was lost to follow-up, discontinued treatment with IMP, initiated treatment with prohibited medication (including hormonal combination therapy), or at Day 336, whichever occurred first.
Time Frame
Randomization to Day 336 (end-of-trial)
Title
Time From Randomization to the First Confirmed (Adjudicated) Unstable Angina Requiring Hospitalization; Percentage of Observed Subjects With Outcome Measure Events During the Trial
Description
Kaplan Meier plots of the cumulative incidence rate by treatment groups were used to depict first confirmed (adjudicated) unstable angina requiring hospitalization. Percentage of observed subjects with outcome measure events during the trial are reported.
Subjects were censored at the time a subject discontinued the trial, was lost to follow-up, discontinued treatment with IMP, initiated treatment with prohibited medication (including hormonal combination therapy), or at Day 336, whichever occurred first.
Time Frame
Randomization to Day 336 (end-of-trial)
Title
Time From Randomization to Death Due to Any Cause; Percentage of Observed Subjects With Outcome Measure Events During the Trial
Description
Kaplan Meier plots of the cumulative incidence rate by treatment groups were used to depict death due to any cause. Percentage of observed subjects with outcome measure events during the trial are reported.
Subjects were censored at the time a subject discontinued the trial, was lost to follow-up, discontinued treatment with IMP, initiated treatment with prohibited medication (including hormonal combination therapy), or at Day 336, whichever occurred first.
Time Frame
Randomization to Day 336 (end-of-trial)
Title
Testosterone Levels at Days 28, 168 and 336 in the Degarelix and Leuprolide Treatment Groups
Description
Median levels and interquartile ranges for serum testosterone at Days 28, 168, and 336 are presented.
Time Frame
Days 28, 168 and 336 (end-of-trial)
Title
Time From Randomization to Failure in Progression-free Survival (PFS); Percentage of Observed Subjects With Outcome Measure Events During the Trial
Description
Time to failure in PFS was defined as the time, measured in days, from randomization to the first occurrence of either death, radiographic disease progression, introduction of additional prostate cancer therapies for progression, or PSA failure.
Subjects who discontinued treatment with IMP or withdrew from the trial were censored at the time of discontinuation/withdrawal.
Kaplan Meier plots of the cumulative incidence rate by treatment groups were used to depict failure in PFS. Percentage of observed subjects with outcome measure events during the trial are reported.
Time Frame
From randomization to end-of-trial for each subject (subjects not censored at Day 336)
Title
Changes From Baseline in International Prostate Symptom Score (IPSS) Total and Quality of Life (QoL) Scores
Description
Lower urinary tract symptoms were measured with the IPSS Version 1 (IPSS-1). The IPSS is a subject-administered questionnaire containing seven items to evaluate symptoms of urinary obstruction (incomplete emptying, frequency, intermittency, urgency, weak stream, straining, nocturia) over the preceding week. Each urinary symptom question was assigned points from 0 to 5 indicating increasing severity of the particular symptom. The total IPSS-1 score was then calculated as summation over the responses for all 7 questions. The total IPSS-1 score was transformed to a scale from 0 (lowest score) to 100 (highest score). Higher scores reflect higher severity of symptoms. The IPSS-1 included an additional single question to assess a subject's QoL in relation to his urinary symptoms; response to this question was analyzed separately and was not included in the total IPSS score. The score was similarly scaled from 0 to 100.
Change from baseline in IPSS Total and QoL scores are presented.
Time Frame
Baseline to Days 168 and 336 (end-of-trial)
Title
Total Number of CV-related Hospitalization Events Over the Duration of the Trial
Description
The total number of CV-related hospitalizations over the duration of the trial was defined as the number of hospitalizations due to CV-related adverse events, observed from the first exposure to IMP up until Day 336 for each subject.
Time Frame
First dose of IMP to Day 336 (end-of-trial)
Title
Total Number of Coronary Artery By-pass Grafting (CABG) or Percutaneous Coronary Intervention (PCI) Procedures Over the Duration of the Trial
Description
The total number of CABG or PCI procedures observed for each subject over the duration of the trial
Time Frame
First dose of IMP to Day 336 (end-of-trial)
Title
Total Number of CV-related Emergency Room (ER) Visit Events Over the Duration of the Trial
Description
CV-related ER visit events (that did not lead to hospitalization) was observed from the first exposure to IMP up until Day 336 for each subject.
Time Frame
First dose of IMP to Day 336 (end-of-trial)
Title
Change in Utility, Based on EuroQol Group 5 Dimensions 5 Levels Questionnaire (EQ-5D-5L)
Description
The EQ-5D-5L essentially consists of 2 systems - the EQ-5D-5L descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-5L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The EQ VAS is an overall estimation of the present health status. The results from the EQ-5D-5L questionnaire were converted into quality adjusted life year (QALY) units.
The QALY is estimated by combining the value of life (utility value) and length of life. Quality adjusted life years are based on a principle assuming that a year of life lived in perfect health is worth 1 QALY and that a year of life lived in a state of less than perfect health is worth less than 1.
Time Frame
Baseline to Day 336 (end-of-trial)
Title
Changes From Baseline in Duke Activity Status Index (DASI) Global Score
Description
The DASI is a self-administered instrument developed to measure functional capacity in subjects with cardiovascular disease (CVD). It contains 12 items referring to the present time, assessing the ability to perform physical tasks in five domains: personal care (1 item), ambulation (4 items), household tasks (4 items), sexual function (1 item) and recreation (2 items). Each question was answered by one of four options: 'yes with no difficulty' / 'yes, but with some difficulty' / 'no, I can't do this' / 'don't do this for other reasons'. A global score was calculated with a higher score indicating a higher functional capacity. The minimum score is 0 and the maximum score is 58.2 points.
Change from baseline in DASI Global score is presented.
Time Frame
Baseline to Days 168 and 336 (end-of-trial)
Title
Changes From Baseline in Cardiac Anxiety Questionnaire (CAQ) Global Score and Score Per Domain
Description
The CAQ is a self-administered questionnaire developed to measure heart-focused anxiety in persons with or without heart disease. It contains 18 items referring to the present time assessing cardiac anxiety in three domains: fear (8 items, each item could be scored between 0 "never" to 4 "always", maximum total score 32), avoidance (5 items, each item could be scored between 0 "never" to 4 "always", maximum total score 20) and attention (5 items, each item could be scored between 0 "never" to 4 "always", maximum total score 20). A higher score indicated greater cardiac anxiety and the total score range was between 0 and 72.
Change from baseline in CAQ Global score and score per domain are presented.
Time Frame
Baseline to Days 168 and 336 (end-of-trial)
Title
Number of Subjects With Adverse Events (AEs)
Description
Adverse events were recorded from signed informed consent until end-of-trial. Adverse events with onset after start of IMP treatment, and within 3 months after (1 month=28 days) last dosing of IMP, were considered 'treatment-emergent' and are presented for the safety analysis set.
Time Frame
Start of IMP treatment until 3 months after last dosing of IMP
Title
Intensity of AEs
Description
The intensity of AE was graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (version 4.02) 5-point scale.
AE were categorized as grade 1 Mild (minor; no specific medical intervention; asymptomatic laboratory findings only; marginal clinical relevance), Grade 2 Moderate (minimal intervention: local intervention; non-invasive intervention), Grade 3 Severe (significant symptoms, requiring hospitalization or invasive intervention; transfusion; elective interventional radiological procedure; therapeutic endoscopy or operation), Grade 4 Life-threatening or disabling (complicated by acute, life-threatening metabolic or CV complications such as circulatory failure, hemorrhage, sepsis. Life-threatening physiologic consequences; need for intensive care or emergent invasive procedure; emergent interventional radiological procedure, therapeutic endoscopy or operation) and Grade 5 Death. Events with grades 3, 4 and 5 were categorized as severe.
Time Frame
Start of IMP treatment until 3 months after last dosing of IMP
Title
Changes in Vital Signs
Description
Number of subjects shifting from normal value(s) in vital signs (pulse and blood pressure) at baseline to clinically significant abnormal value(s) at end-of-trial are presented.
Note: Only subjects with appropriate baseline and post-baseline data are included in the evaluation.
Time Frame
Baseline to Day 336 (end-of-trial)
10. Eligibility
Sex
Male
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Advanced prostate cancer
Indication to initiate androgen deprivation therapy (ADT)
Predefined cardiovascular disease
Exclusion Criteria:
Previous or current hormonal management of prostate cancer (unless terminated at least 12 months prior to trial)
Acute cardiovascular disease in the previous 30 days
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Global Clinical Compliance
Organizational Affiliation
Ferring Pharmaceuticals
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Susan Slovin, MD
Organizational Affiliation
Sidney Kimmel Center for Urologic and Prostate Cancers, Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
John Alexander, MD, MHS
Organizational Affiliation
Division of Cardiovascular Medicine, Duke Clinical Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Urology Center of Alabama PC
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35209
Country
United States
Facility Name
Arizona Institute of Urology
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85704
Country
United States
Facility Name
Urological Associates of Southern Arizona
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85715
Country
United States
Facility Name
University of Arizona College of Medicine
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724
Country
United States
Facility Name
Urology Associates, PA
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72211
Country
United States
Facility Name
Pacific Cancer Medical Center, Inc.
City
Anaheim
State/Province
California
ZIP/Postal Code
92801
Country
United States
Facility Name
San Diego Clinical Trials
City
La Mesa
State/Province
California
ZIP/Postal Code
91942
Country
United States
Facility Name
Clinical Trials Research
City
Lincoln
State/Province
California
ZIP/Postal Code
95648
Country
United States
Facility Name
VA Greater Los Angeles Healthcare System
City
Los Angeles
State/Province
California
ZIP/Postal Code
90073
Country
United States
Facility Name
University of California, Irvine Medical Center
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Skyline Urology
City
Torrance
State/Province
California
ZIP/Postal Code
90505
Country
United States
Facility Name
Innovative Clinical Research Institute
City
Whittier
State/Province
California
ZIP/Postal Code
90603
Country
United States
Facility Name
Urology Center of Colorado
City
Denver
State/Province
Colorado
ZIP/Postal Code
80211
Country
United States
Facility Name
Yale University
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06519
Country
United States
Facility Name
Urologic Surgeons of Washington
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20036
Country
United States
Facility Name
Mount Sinai Comprehensive Cancer Center
City
Miami Beach
State/Province
Florida
ZIP/Postal Code
33140
Country
United States
Facility Name
San Marcus Research Clinic Inc
City
Miami
State/Province
Florida
ZIP/Postal Code
33014
Country
United States
Facility Name
Clinical Research Center of Florida
City
Pompano Beach
State/Province
Florida
ZIP/Postal Code
33060
Country
United States
Facility Name
Florida Urology Partners
City
Tampa
State/Province
Florida
ZIP/Postal Code
33615
Country
United States
Facility Name
Comprehensive Urologic Care
City
Lake Barrington
State/Province
Illinois
ZIP/Postal Code
60010
Country
United States
Facility Name
Springfield Clinic LLP
City
Springfield
State/Province
Illinois
ZIP/Postal Code
62703
Country
United States
Facility Name
Urology of Indiana LLC
City
Greenwood
State/Province
Indiana
ZIP/Postal Code
46032
Country
United States
Facility Name
First Urology PSC
City
Jeffersonville
State/Province
Indiana
ZIP/Postal Code
47130
Country
United States
Facility Name
Iowa Clinic
City
West Des Moines
State/Province
Iowa
ZIP/Postal Code
50266
Country
United States
Facility Name
University of Kansas Medical Center Research Institute, Inc.
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
Kansas City Urology Care
City
Lenexa
State/Province
Kansas
ZIP/Postal Code
66214
Country
United States
Facility Name
Regional Urology, LLC
City
Shreveport
State/Province
Louisiana
ZIP/Postal Code
71106
Country
United States
Facility Name
Chesapeake Urology Associates, P.A.
City
Towson
State/Province
Maryland
ZIP/Postal Code
21204
Country
United States
Facility Name
Delaware Valley Urology LLC Westhampton
City
Mount Laurel
State/Province
New Jersey
ZIP/Postal Code
08054
Country
United States
Facility Name
Holy Name Medical Center
City
Teaneck
State/Province
New Jersey
ZIP/Postal Code
07666
Country
United States
Facility Name
Urology Group of New Mexico PC
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87109
Country
United States
Facility Name
Montefiore Medical Center PRIME
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
Facility Name
Advanced Urology Centers of New York Elmont Division
City
Elmont
State/Province
New York
ZIP/Postal Code
11003
Country
United States
Facility Name
SUNY Upstate Medical University
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Veterans Affairs Medical Center-Salisbury, NC
City
Salisbury
State/Province
North Carolina
ZIP/Postal Code
28144
Country
United States
Facility Name
Signal Point Clinical Research Center
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45409
Country
United States
Facility Name
Clinical Research Solutions PC
City
Middleburg Heights
State/Province
Ohio
ZIP/Postal Code
44130
Country
United States
Facility Name
Urologic Consultants of Southeaster PA LLP
City
Bala-Cynwyd
State/Province
Pennsylvania
ZIP/Postal Code
19004
Country
United States
Facility Name
Lancaster Urology
City
Lancaster
State/Province
Pennsylvania
ZIP/Postal Code
17604
Country
United States
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Ralph H. Johnson VA Medical Center
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29401
Country
United States
Facility Name
Medical University of South Carolina (MUSC)
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
Erlanger Health System
City
Chattanooga
State/Province
Tennessee
ZIP/Postal Code
37403
Country
United States
Facility Name
Urology of Virginia
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23462
Country
United States
Facility Name
Seattle Urology Research Center
City
Burien
State/Province
Washington
ZIP/Postal Code
98166
Country
United States
Facility Name
University of Washington School of Medicine
City
Seattle
State/Province
Washington
ZIP/Postal Code
98195
Country
United States
Facility Name
Medical College of Wisconsin, Inc.
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
The Male Health Centre Euroscope Inc
City
Barrie
State/Province
Ontario
Country
Canada
Facility Name
J. Giddens Medicine Professional Corporation
City
Brampton
State/Province
Ontario
Country
Canada
Facility Name
G. Kenneth Jansz Medicine Professional Corporation
City
Burlington
State/Province
Ontario
Country
Canada
Facility Name
Urology Associates Urologic Medical Research
City
Kitchener
State/Province
Ontario
Country
Canada
Facility Name
London Health Sciences Centre
City
London
State/Province
Ontario
Country
Canada
Facility Name
Femalemale Health Centres
City
Oakville
State/Province
Ontario
Country
Canada
Facility Name
Princess Margaret Cancer Centre
City
Toronto
State/Province
Ontario
Country
Canada
Facility Name
Uro Laval
City
Laval
State/Province
Quebec
Country
Canada
Facility Name
Jewish General Hospital / McGill University
City
Montréal
State/Province
Quebec
Country
Canada
Facility Name
CHU de Québec -Hôtel-Dieu de Québec
City
Québec
Country
Canada
Facility Name
Fakultni nemocnice Olomouc
City
Olomouc
Country
Czechia
Facility Name
Fakultni nemocnice Ostrava
City
Ostrava
Country
Czechia
Facility Name
Multiscan s.r.o.
City
Pardubice
Country
Czechia
Facility Name
Urocentrum Plzen
City
Plzen
Country
Czechia
Facility Name
Fakultni nemocnice v Motole
City
Praha
Country
Czechia
Facility Name
Proton Therapy Center Czech s.r.o.
City
Praha
Country
Czechia
Facility Name
Oblastni nemocnice Pribram a.s.
City
Příbram
Country
Czechia
Facility Name
Krajska zdravotni a.s. - Masarykova nemocnice v Usti nad Labem o.z.
City
Ústí Nad Labem
Country
Czechia
Facility Name
Keski-Suomen keskussairaala
City
Jyväskylä
Country
Finland
Facility Name
Tampereen yliopistollinen
City
Tampere
Country
Finland
Facility Name
Institut Sainte Catherine
City
Avignon
Country
France
Facility Name
Groupe Hospitalier Pellegrin Tripode
City
Bordeaux
Country
France
Facility Name
Hôpital Henri Mondor
City
Créteil
Country
France
Facility Name
CHU de Grenoble - Hôpital Albert Michallon
City
Grenoble
Country
France
Facility Name
CH de Libourne- Hopital Robert Boulin
City
Libourne
Country
France
Facility Name
Hopital Claude Huriez - CHU Lille
City
Lille
Country
France
Facility Name
Hopital Edouard Herriot - CHU Lyon
City
Lyon
Country
France
Facility Name
Centre Hospitalier Régional Universitaire de Tours
City
Nantes
Country
France
Facility Name
Hopital Bichat - Claude Bernard
City
Paris
Country
France
Facility Name
Clinique Saint Jean Languedoc
City
Toulouse
Country
France
Facility Name
Universitaetsklinikum Freiburg
City
Freiburg
State/Province
Baden Wuerttemberg
Country
Germany
Facility Name
Urologische Gemeinschaftspraxis
City
Kirchheim Unter Teck
State/Province
Baden Wuerttemberg
Country
Germany
Facility Name
Urologische Gemeinschaftspraxis
City
Herzogenaurach
State/Province
Bayern
Country
Germany
Facility Name
Staedtisches Klinikum Braunschweig GmbH - Standort Salzdahlumer
City
Braunschweig
State/Province
Niedersachsen
Country
Germany
Facility Name
Klinikum Oldenburg gGmbH
City
Oldenburg
State/Province
Niedersachsen
Country
Germany
Facility Name
Kliniken Maria Hilf GmbH
City
Moenchengladbach
State/Province
Nordrhein Westfalen
Country
Germany
Facility Name
Praxisklinik Urologie Rhein Ruhr
City
Mülheim
State/Province
Nordrhein Westfalen
Country
Germany
Facility Name
Krankenhaus Martha-Maria Halle-Doelau
City
Halle
State/Province
Sachsen Anhalt
Country
Germany
Facility Name
Facharztpraxis für Urologie
City
Lutherstadt Eisleben
State/Province
Sachsen Anhalt
Country
Germany
Facility Name
Staedtisches Klinikum Dresden Standort Dresden-Friedrichstadt
City
Dresden
State/Province
Sachsen
Country
Germany
Facility Name
Urologie am Nordplatz
City
Leipzig
State/Province
Sachsen
Country
Germany
Facility Name
Gynaekologisches Zentrum Bonn-Friedensplatz
City
Bonn
Country
Germany
Facility Name
Central Clinic of Athens
City
Athens
Country
Greece
Facility Name
General Hospital of Athens "Alexandra"
City
Athens
Country
Greece
Facility Name
T.Y.P.E.T. Hygeias Melathron Hospital
City
Athens
Country
Greece
Facility Name
University General Hospital of Heraklion
City
Heraklion
Country
Greece
Facility Name
University of Patras Medical School
City
Patras
Country
Greece
Facility Name
General Hospital Papageorgiou
City
Thessaloníki
Country
Greece
Facility Name
Swietokrzyskie Centrum Onkologii
City
Kielce
Country
Poland
Facility Name
Provita Profamilia
City
Piotrków Trybunalski
Country
Poland
Facility Name
WroMedica
City
Wrocław
Country
Poland
Facility Name
DERMED Centrum Medyczne Sp. z o.o.
City
Łódź
Country
Poland
Facility Name
SBHI of Sverdiovsk Region "Sverdiovsk Regional Clinical Hospital #1
City
Ekaterinburg
Country
Russian Federation
Facility Name
City Clinical Hospital n.a. Botkin
City
Moscow
Country
Russian Federation
Facility Name
FSBI "Moscow scientific research oncology institute"
City
Moscow
Country
Russian Federation
Facility Name
FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin"
City
Moscow
Country
Russian Federation
Facility Name
SBEI HPE "Moscow State Medical and Dentistry University n.a. A. I. Evdokimov"
City
Moscow
Country
Russian Federation
Facility Name
FBHI Privolzhskiy District Medical Centre FMBA of Russia
City
Nizhniy Novgorod
Country
Russian Federation
Facility Name
Medical Center Avitsenna
City
Novosibirsk
Country
Russian Federation
Facility Name
BHI of Omsk region "Clinical Oncology Dispensary
City
Omsk
Country
Russian Federation
Facility Name
FFSBI "The Nikiforov Russian Center of Emergency and Radiation Medicine"
City
Saint-Petersburg
Country
Russian Federation
Facility Name
CUIMED s.r.o.
City
Bratislava
Country
Slovakia
Facility Name
Urocentrum Bratislava s.r.o.
City
Bratislava
Country
Slovakia
Facility Name
Vychodoslovensky onkologicky ustav, a.s.
City
Kosice
Country
Slovakia
Facility Name
Nemocnica Kosice-Saca, a.s.
City
Košice
Country
Slovakia
Facility Name
Zeleznicna nemocnica Kosice
City
Košice
Country
Slovakia
Facility Name
UROCENTRUM LEVICE s.r.o.
City
Levice
Country
Slovakia
Facility Name
UROAMB s.r.o.
City
Liptovský Mikuláš
Country
Slovakia
Facility Name
Univerzitna nemocnica Martin
City
Martin
Country
Slovakia
Facility Name
Fakultna nemocnica Nitra
City
Nitra
Country
Slovakia
Facility Name
UROEXAM, spol. s r.o.
City
Nitra
Country
Slovakia
Facility Name
MILAB s.r.o.
City
Prešov
Country
Slovakia
Facility Name
MIRAMED s.r.o
City
Rimavska Sobota
Country
Slovakia
Facility Name
UROCENTRUM SALA s.r.o.
City
Sala
Country
Slovakia
Facility Name
Privatna Urologicka ambulancia
City
Trenčín
Country
Slovakia
Facility Name
Fakultna nemocnica s poliklinikou Zilina
City
Žilina
Country
Slovakia
Facility Name
Groote Schuur Hospital Department of Urology
City
Cape Town
State/Province
Western Cape
Country
South Africa
Facility Name
Prince Philip Hospital
City
Llanelli
State/Province
Carmarthenshire
Country
United Kingdom
Facility Name
Charing Cross Hospital
City
London
State/Province
Greater London
Country
United Kingdom
Facility Name
Scunthorpe General Hospital
City
Scunthorpe
State/Province
Lincolnshire
Country
United Kingdom
Facility Name
St Peter's Hospital
City
Chertsey
State/Province
Surrey
Country
United Kingdom
Facility Name
Royal Hallamshire Hospital
City
Sheffield
State/Province
West Midlands
Country
United Kingdom
Facility Name
Addenbrooke's Hospital
City
Cambridge
Country
United Kingdom
Facility Name
Royal Devon and Exeter Hospital (Wonford)
City
Exeter
Country
United Kingdom
Facility Name
Salford Royal
City
Salford
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
34459214
Citation
Lopes RD, Higano CS, Slovin SF, Nelson AJ, Bigelow R, Sorensen PS, Melloni C, Goodman SG, Evans CP, Nilsson J, Bhatt DL, Clarke NW, Olesen TK, Doyle-Olsen BT, Kristensen H, Arney L, Roe MT, Alexander JH; PRONOUNCE Study Investigators. Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Prostate Cancer: The Primary Results of the PRONOUNCE Randomized Trial. Circulation. 2021 Oct 19;144(16):1295-1307. doi: 10.1161/CIRCULATIONAHA.121.056810. Epub 2021 Aug 30. Erratum In: Circulation. 2021 Oct 19;144(16):e273.
Results Reference
derived
PubMed Identifier
34350976
Citation
Zengerling F, Jakob JJ, Schmidt S, Meerpohl JJ, Blumle A, Schmucker C, Mayer B, Kunath F. Degarelix for treating advanced hormone-sensitive prostate cancer. Cochrane Database Syst Rev. 2021 Aug 5;8(8):CD012548. doi: 10.1002/14651858.CD012548.pub2.
Results Reference
derived
PubMed Identifier
34396210
Citation
Melloni C, Slovin SF, Blemings A, Goodman SG, Evans CP, Nilsson J, Bhatt DL, Zubovskiy K, Olesen TK, Dugi K, Clarke NW, Higano CS, Roe MT; PRONOUNCE Investigators. Cardiovascular Safety of Degarelix Versus Leuprolide for Advanced Prostate Cancer: The PRONOUNCE Trial Study Design. JACC CardioOncol. 2020 Mar 17;2(1):70-81. doi: 10.1016/j.jaccao.2020.01.004. eCollection 2020 Mar.
Results Reference
derived
Learn more about this trial
A Trial Comparing Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Advanced Prostate Cancer and Cardiovascular Disease
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