Routine Cardiac Screening in Sarcoidosis Patients (PAPLAND)

A Randomized Screening Trial for Cardiac Sarcoidosis (CS) in Patients Seen During Routine Clinical Care Who Have Not Been Clinically Suspected to Have (CS), Comparing the Addition of Echocardiogram and Ambulatory ECG to Standard of Care.

This protocol is an unblended randomized screening trial will have consecutive patients with no suggestion of cardiac sarcoidosis according to usual screening enroll in an enhanced screening protocol. The routine clinical care is to gather patient's history of symptoms and under go an ECG. If a patient has an abnormal results in standard screening, they typically have further evaluations as part of their routine medical care. These tests might include an echocardiogram, ambulatory ECG, and advanced cardiac imaging (MRI, PET scan as per local practice). A patient that has normal results on standard screening will be randomly assigned to enhanced screening at each center. Half the patients will be randomized to usual follow-up (annual symptom assessment and ECG) and the other half will be assigned to the enhanced screening (echocardiogram and ambulatory ECG at enrollment and at 24 months).

The investigators hypothesize that screening using conventional history, physical and ECG in the general sarcoidosis population, followed by appropriate advanced imaging testing, will result in the identification of a higher percentage of ascertained cardiac sarcoidosis than has been reported historically (2-5%). The investigators hypothesize that routine use of echocardiogram with strain and ambulatory ECG will identify additional patients who will have advanced imaging abnormalities or who meet criteria for cardiac sarcoidosis. The investigators further hypothesize that re-screening patients after 24 months with repeat echocardiogram and ambulatory ECG will identify additional patients with suspicion for cardiac sarcoidosis who had no abnormalities on the standard screening tests.

Study Overview

• Status: Recruiting
• Conditions: Sarcoidosis; Cardiac Sarcoidosis; Boeck's Disease; Besnier-Boeck Disease
• Intervention / Treatment: Diagnostic test: Enhanced Screening Protocol for Cardiac Sarcoidosis.; Diagnostic test: Routine Screening for Suspected Cardiac Sarcoidosis

Detailed Description

Cardiac involvement is among the most feared complications of sarcoidosis, and it is the second leading cause of death from sarcoidosis. Autopsy studies and serial imaging studies in patients without cardiac symptoms suggest that approximately 25% of U.S. sarcoidosis patients have evidence of cardiac involvement. 3 Major manifestations of cardiac sarcoidosis include conduction delays, dysrhythmias, and cardiomyopathy. Given the increased recognition of cardiac involvement, prompt screening and diagnosis of cardiac sarcoidosis has been emphasized as a key priority for sarcoidosis research. Screening for cardiac sarcoidosis conventionally has relied on symptoms and electrocardiogram. However, there are no validated screening instruments for symptom assessment, and the usefulness of individual components of the medical history (e.g. palpitations, chest pain, presyncope) has not been assessed. In one study, symptom assessment was found to be less than 50% sensitive for identification of individuals with abnormal cardiac imaging studies. ECG performed poorly, with less than 10% sensitivity. Holter monitoring and echocardiogram were more sensitive than ECG in that study, identifying 50% and 25%, respectively, of those with imaging findings suggesting cardiac sarcoidosis (CS). The intensity of screening for CS in unselected sarcoidosis patients is controversial. The Heart Rhythm Society working group could not agree that echocardiogram or ambulatory ECG added significantly to conventional testing of eliciting cardiac symptoms and ECG; therefore, the working group was unable to recommend adding these procedures as a routine for all sarcoidosis patients. In a large series of Greek non-cardiac sarcoidosis patients, echocardiogram and ambulatory ECG added little prognostic information to usual care. On the other hand, more sophisticated echocardiographic techniques such as speckle tracking seem to provide independent prognostic information. In a second study, Holter monitoring and echocardiography abnormalities were both more common in those with MRI findings consistent with CS, although the usefulness of the tests disappeared in multivariable analysis. While history and ECG are considered the standard of care at present, there is a continuing need to identify markers of poor outcomes. Cardiac MRI and/or cardiac FDG-PET scan can identify large proportions of individuals with asymptomatic imaging abnormalities, but these scans are expensive, require specialized expertise to interpret, require radiation (PET scan) and are likely impractical for widespread use in all sarcoidosis patients. A second unresolved issue concerning screening for cardiac sarcoidosis is the frequency of re-screening sarcoidosis patients who demonstrate no evidence for cardiac sarcoidosis on an initial screen. The investigators hypothesize that screening using conventional history, physical and ECG in the general sarcoidosis population, followed by appropriate advanced imaging testing, will result in the identification of a higher percentage of ascertained cardiac sarcoidosis than has been reported historically (2-5%). The investigators hypothesize that routine use of echocardiogram with strain and ambulatory ECG will identify additional patients who will have advanced imaging abnormalities or who meet criteria for cardiac sarcoidosis. The investigators further hypothesize that re-screening patients after 24 months with repeat echocardiogram and ambulatory ECG will identify additional patients with suspicion for cardiac sarcoidosis who had no abnormalities on the initial screening tests.

Aims

1. To evaluate the rate of diagnosis of cardiac sarcoidosis during standard of care clinical practice that relies on patient symptoms and ECG.
2. To evaluate whether second-tier screening tests (echocardiogram and ambulatory ECG) improve the rate of diagnosis of cardiac sarcoidosis beyond conventional screening methods.
3. To evaluate the rate of diagnosis of cardiac sarcoidosis in sarcoidosis patients who had initial negative conventional and second-tier screening tests after undergoing these screening tests again at two years.

• Study Type: Interventional
• Enrollment (Estimated): 600
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Tricha Shivas, MBe; Phone Number: 3122410400; Email: tricha@stopsarcoidosis.org
• Study Contact Backup: Name: Timothy Legenzoff; Phone Number: 312-341-0500; Email: Tim@stopsarcoidosis.org

Study Locations

• Netherlands
  • Nieuwegein
    • Koekoekslaan, Nieuwegein, Netherlands
      • Recruiting
      • St. Antonius
      • Contact: Marcel Veltkamp, MD
      • Principal Investigator: Marcel Veltkamp, MD
• United Kingdom
  • Cambridge, United Kingdom
    • Recruiting
    • Royal Papworth Hospital
    • Contact: Helen Holcombe; Phone Number: +44 (0) 1223 639822; Email: Helen.holcombe@nhs.net
    • Principal Investigator: Muhunthan Thillai
• United States
  • Colorado
    • Denver, Colorado, United States, 80206
      • Recruiting
      • National Jewish Health
      • Contact: Briana Barkes
      • Principal Investigator: Lisa Maier, MD
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Recruiting
      • University of Illinois Medical Center At Chicago
      • Contact: Hasib Zabih; Phone Number: 312-355-0601; Email: hzabih2@uic.edu
      • Principal Investigator: Nadera Sweiss, MD
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Northwestern University Medicine
      • Contact: Isaac Goldberg
      • Principal Investigator: Peter Sporn, MD
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa Hospital
      • Contact: Brenda Werner
      • Principal Investigator: Nabeel Y Hamzeh, MD
  • New York
    • Albany, New York, United States, 12208
      • Recruiting
      • Albany Medical Center
      • Contact: Rachel Vancavage
      • Principal Investigator: Marc Judson, MD
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Recruiting
      • University of Cincinnati Medical Center
      • Contact: Rebecca Reeves; Phone Number: 513-584-5226; Email: reevesrc@ucmail.uc.edu
      • Principal Investigator: Robert Baughman, MD
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic
      • Contact: Allison Wimer; Phone Number: 216-444-9975
      • Principal Investigator: Daniel Culver, DO
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Terminated
      • Penn Medicine
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Medical University of South Carolina
      • Contact: Ashley Warden
      • Principal Investigator: W. Ennis James, MD
  • Washington
    • Seattle, Washington, United States, 98195
      • Recruiting
      • University of Washington Medical Center
      • Contact: Chessa Goss
      • Principal Investigator: Ganesh Raghu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Diagnosis of sarcoidosis as per The American Thoracic Society guidelines
2. First visit to the enrolling center
3. Intent to continue care at the enrolling center at least annually

Exclusion Criteria:

1. Referred to the enrolling center to evaluate for suspected cardiac sarcoidosis.
2. Pre-existing high suspicion for cardiac sarcoidosis, defined as having had cardiac MRI or cardiac PET scan, even if it was ordered by other institutions.
3. Severe sarcoidosis or other disease conferring a high likelihood of death or transplant within the next year
4. Unwilling or unable to undergo echocardiography and ambulatory ECG

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Enhanced Screening Protocol For Cardiac Sarcoidosis; Arm will be randomly assigned to undergo enhanced screening methods (ambulatory ECG and echocardiogram) at month 0 and month 24, as well as a phone call/chart review at month 12.	Diagnostic test: Enhanced Screening Protocol for Cardiac Sarcoidosis.; To utilize enhanced screening tests for cardiac sarcoidosis in an undiagnosed and potentially under-diagnosed patient population to determine the rate of missed cardiac sarcoidosis diagnosis. Following testing by the standard screening tests, this intervention includes a subsequent echocardiogram and a wearable ECG, also known as a Holter Monitor or ambulatory ECG.; Other Names: Echocardiogram and ambulatory ECG
Active Comparator: Routine Screening for Suspected Cardiac Sarcoidosis; Arm will be randomly assigned for the routine standard of care/no intervention with enhanced screening methods. They will be offered the EKG and symptom check at months 0 and 24, as well as a phone call/chart review at month 12.	Diagnostic test: Routine Screening for Suspected Cardiac Sarcoidosis; To utilize standard of care screening tests for cardiac sarcoidosis. This includes symptom check and a standard ECG.; Other Names: Symptom check and standard ECG.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Positive result found from enhanced cardiac sarcoidosis screening at initial visit (sensitivity)	To evaluate whether second-tier screening tests (echocardiogram and ambulatory ECG) improve the rate of diagnosis of cardiac sarcoidosis beyond conventional screening methods.	Day 1
Positive result found on enhanced cardiac screening at month 12 (sensitivity)	To evaluate whether second-tier screening tests (echocardiogram and ambulatory ECG) improve the rate of diagnosis of cardiac sarcoidosis beyond conventional screening methods during chart review.	Month 12
Positive result found from enhanced cardiac screening at month 24 (sensitivity)	To evaluate the rate of diagnosis of cardiac sarcoidosis in sarcoidosis patients who had initial negative conventional and second-tier screening tests after undergoing these screening tests again at two years	Month 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Positive result from study cohort	To evaluate the rate of diagnosis of cardiac sarcoidosis in study cohort after 10 years.	Up to 120 months after study completion
Rate of diagnosis of cardiac sarcoidosis during standard of care of patient symptoms and ECG.	To evaluate the rate of diagnosis of cardiac sarcoidosis during standard of care clinical practice that relies on patient symptoms and ECG.	Up to 24 months from day 1

Collaborators and Investigators

• Sponsor: Foundation for Sarcoidosis Research
• Investigators: Principal Investigator: Dan Culver, DO, The Cleveland Clinic; Principal Investigator: Muhunthan Thillai, MBBS, Royal Papworth Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 5, 2019
• Primary Completion (Estimated): April 1, 2029
• Study Completion (Estimated): April 1, 2029

Study Registration Dates

• First Submitted: March 25, 2019
• First Submitted That Met QC Criteria: April 2, 2019
• First Posted (Actual): April 3, 2019

Study Record Updates

• Last Update Posted (Actual): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 18, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: sarcoidosis; cardiac sarcoidosis; cardiac sarcoidosis screening
• Additional Relevant MeSH Terms: Immune System Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Hypersensitivity; Hypersensitivity, Delayed; Sarcoidosis
• Other Study ID Numbers: CSN504-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

All data will be housed in a secured RedCap database. Protected health information (PHI) will be available only to the individual institutions, and the RedCap database will not house such data.

Each subject will be entered into the database using a unique subject identifying number.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No