Prediction of the PRONOUNCE Prostate Cancer Trial in Healthcare Claims Data

July 25, 2023 updated by: Shirley Vichy Wang, Brigham and Women's Hospital
Investigators are building an empirical evidence base for real world data through large-scale replication of randomized controlled trials. The investigators' goal is to understand for what types of clinical questions real world data analyses can be conducted with confidence and how to implement such studies.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a non-randomized, non-interventional study that is part of the RCT DUPLICATE initiative (www.rctduplicate.org) of the Brigham and Women's Hospital, Harvard Medical School. It is intended to replicate, as closely as is possible in healthcare insurance claims data, the trial listed below/above. Although many features of the trial cannot be directly replicated in healthcare claims, key design features, including outcomes, exposures, and inclusion/exclusion criteria, were selected to proxy those features from the trial. Randomization is also not replicable in healthcare claims data but was proxied through a statistical balancing of measured covariates according to standard practice. Investigators assume that the RCT provides the reference standard treatment effect estimate and that failure to replicate RCT findings is indicative of the inadequacy of the healthcare claims data for replication for a range of possible reasons and does not provide information on the validity of the original RCT finding.

Study Type

Observational

Enrollment (Actual)

14417

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02120
        • Brigham and Women's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

N/A

Sampling Method

Non-Probability Sample

Study Population

Subjects were selected on the basis of having at least one diagnosis code indicating prostate cancer, male sex, and a history of artherosclerotic cardiovascular disease. In contrast to the the PRONOUNCE RCT trial, patients cannot be required to have had established tumor staging information, angiography-verified stenosis/occlusion of vessels, and a lack of planned cardiac surgery at the time of treatment initiation due to poor capture of this information administrative data. All patients were required to have continuous enrollment for 365 days prior to cohort entry to ensure incident use of the study drugs.

Description

Please see https://drive.google.com/drive/folders/1WD618wrywYjEaXzfLTcuK-VCcnb6b-gV for full code and algorithm definitions.

Eligible cohort entry dates:

The degarelix indication for treatment of prostate cancer was approved by the FDA on Dec 24, 2008. Leuprolide was initially approved for the same indication prior to Dec 24, 2008.

IBM MarketScan: Dec 24, 2008 - December 31, 2018 (end of available data) Optum CDM: Dec 24, 2008 - June 30, 2020 (end of available data) CMS Diabetes: Dec 24, 2008 - Dec 31, 2017 (end of available data)

Inclusion Criteria:

  • Histologically confirmed adenocarcinoma of the prostate
  • Pre-existing ASCVD (confirmed diagnosis, documented) according to a least 1 of the following criteria:
  • Previous MI >= 30 days before randomization
  • Previous revascularization procedure >= 30 days before randomization
  • Coronary artery: stent placement/balloon angioplasty or coronary artery bypass graft surgery
  • Carotid artery: stent placement/balloon angioplasty or endarterectomy surgery
  • Iliac, femoral, popliteal arteries: stent placement/balloon angioplasty or vascular bypass surgery

Exclusion Criteria:

  • Treatment naivety (ADT)
  • Previous or current hormonal management of prostate cancer including surgical castration, any hormonal manipulation, or any previous neoadjuvant/adjuvant hormonal therapy, unless treatment was terminated more than 12 months prior to enrollment
  • Uncontrolled Type 1 or Type 2 diabetes mellitus
  • Uncontrolled hypertension
  • A history of congenital long QT syndrome or risk factors for Torsade de pointes ventricular arrhythmias
  • MI; stroke; or coronary, carotid, or peripheral artery revascularization

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Degarelix
Reference group
Drug: Degarelix
Degarelix dispensing claim is used as the reference group.
Leuprolide
Exposure group
Drug: Leuprolide
Leuprolide dispensing claim is used as the exposure group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Major Adverse Cardiovascular Events (MACE)
Time Frame: Through study completion (earliest of 336 days or censoring)
Composite of all-cause mortality, nonfatal MI, and nonfatal stroke
Through study completion (earliest of 336 days or censoring)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
All-Cause Mortality
Time Frame: Through study completion (earliest of 336 days or censoring)
Component of MACE
Through study completion (earliest of 336 days or censoring)
Nonfatal MI
Time Frame: Through study completion (earliest of 336 days or censoring)
Component of MACE
Through study completion (earliest of 336 days or censoring)
Nonfatal Stroke
Time Frame: Through study completion (earliest of 336 days or censoring)
Component of MACE
Through study completion (earliest of 336 days or censoring)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Brigham and Women's Hospital

Investigators

  • Principal Investigator: Shirley Wang, PhD, ScM, Brigham and Women's Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 21, 2019

Primary Completion (Actual)

August 1, 2021

Study Completion (Actual)

August 1, 2021

Study Registration Dates

First Submitted

May 17, 2021

First Submitted That Met QC Criteria

May 18, 2021

First Posted (Actual)

May 24, 2021

Study Record Updates

Last Update Posted (Actual)

July 27, 2023

Last Update Submitted That Met QC Criteria

July 25, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2018P002966-DUP-PRONOUNCE

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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