Cardiac Sarcoidosis Multi-Center Prospective Cohort

Cardiac Sarcoidosis Clinical Trial

— CHASM-CS  

Official title:

Cardiac Sarcoidosis Multi-Center Prospective Cohort Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01477359
• Other study ID #: UOHI-04
• Status: Recruiting
• Start date: August 2012
• Est. completion date: December 2025

Study information

• Verified date: May 2024
• Source: Ottawa Heart Institute Research Corporation
• Contact: Janine E Ryan, BA(H), CCRP
• Phone: 613-696-7000
• Email: jryan[@]ottawaheart.ca
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Recent data has shown that sarcoidosis, presenting initially with cardiac manifestations (CS) of either conduction system disease or cardiomyopathy and sustained VT, is not uncommon. A Canadian physician survey found that most physicians do not investigate for CS as a possibility in these situations. Thus many patients with clinically important CS are going un-diagnosed. A study from Finland showed that missing the diagnosis of CS in these patients' leads to significant mortality and morbidity.

There are no published clinical consensus guidelines on treatment of CS. Corticosteroid therapy is advocated by most experts. This is based on very modest data from small retrospective observational studies using variable definitions of clinical response. The effect of corticosteroid treatment on the clinical course of CS has not been studied in prospective studies and will be one of the aims of this project. Recent physician surveys regarding CS, in Canada and the US, found that current clinical practice varies widely. The 2008 American College of Cardiology/American Heart Association/Heart Rhythm society guidelines recommend implantation of a defibrillator (Class IIa recommendation) to prevent sudden cardiac death. The most recent Canadian device therapy guidelines do not mention CS.

A multi-center collaborative approach to study CS is greatly needed." The investigators propose exactly that i.e. a multi-center prospective cohort to start to answer clinical questions. The investigators have formed the CANADIAN CARDIAC SARCOIDOSIS RESEARCH GROUP. The group includes respirologists with an interest in sarcoidosis, cardiac electrophysiologists, cardiac imaging specialists with extensive experience in imaging of sarcoidosis and biostatisticians. The research will be in two phases; a registry of current diagnostic approaches, treatment and prognosis, and a randomized clinical trial of the effect of corticosteroid treatment on the clinical course of cardiac sarcoidosis.

Description:

Baseline assessment of Clinically Manifest CS patients consists of: history, echocardiogram, ECG, chest CT scan, FDG-PET scan, blood for biomarkers within 2 months of the PET scan, cardiac MRI and possibly a signal average ECG and biopsy (encouraged-either endomyocardial or extra-cardiac).

Follow-up and clinical management of clinically manifest patients diagnosed with CS will occur at 3-6 months with a repeat FDG-PET scan and blood biomarkers. Follow-up will then be annually with an echo and ECG. Treatment with steroids/immunosuppressants and device therapy will be at the discretion of the treating physician.

Baseline assessment of patients diagnosed with extra-cardiac sarcoidosis and being screened for CS consists of: history, echocardiogram, ECG, holter, chest CT scan, biopsy, and cardiac MRI (CMR). If the CMR is suggestive of CS the patient will be have a FDG-PET scan done and be followed as a Clinically Silent patient. They will be contacted every 2 years. If the CMR is negative the patient will be followed as a extra-cardiac sarcoidosis patient with no evidence of CS and be in the control group. They will be contacted at 5 years and at the time of study completion.

All patients will be followed until the last patient recruited has been followed for 4 years.

The occurrence of the primary and secondary outcomes will be assessed in treated and untreated patients.

There will be 2 imaging core labs. The PET core lab will be located at UOHI under the direction of Dr. Robert Beanlands. The CMR core lab will be under the direction of Dr. Mathias Friedrich (McGill University). All scans will be read in the core labs by physicians who are blinded to the clinical details of the patients.

The Biomarker core lab will be at The University of Ottawa Heart Institute under the leadership of Dr P Liu.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1500
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

Inclusion Criteria:

To diagnose Clinically Manifest CS all following criteria must be met:

(i) Positive biopsy* for Sarcoid (either EMB or extra-cardiac) AND/OR (ii) CT Chest highly suggestive of pulmonary sarcoidosis AND (iii) one or more of the following clinical features:

• advanced conduction system disease (sustained Mobitz II AV block or third degree AV block)

• non- sustained or sustained ventricular arrhythmia

• ventricular dysfunction (LVEF < 50% and/or RVEF < 40%) AND (iv) No alternative explanation for clinical features AND (v) FDG-PET suggestive of active CS

To diagnose clinically silent CS all of the following criteria must be met

(i) Biopsy proven extra-cardiac sarcoidosis

AND/OR (ii) CT Chest highly suggestive of pulmonary sarcoidosis

AND (iii) CMR suggestive of cardiac sarcoidosis

AND (iv) Does not have criteria for clinically manifest CS ie. should not have any of following

• advanced conduction system disease (sustained Mobitz II AV block or third degree AV block)

• non- sustained or sustained ventricular arrhythmia

• ventricular dysfunction (LVEF < 50% and/or RVEF < 40%)

Patients with negative CMR will be designated as 'extra-cardiac sarcoidosis with no evidence of CS' and followed as control

Exclusion Criteria:

• unable or unwilling to provide informed consent

• patients who are pregnant or lactating

• patients with known claustrophobia

• age < 18 years

Related Conditions & MeSH terms

• Cardiac Sarcoidosis
• Sarcoidosis

Locations

Country	Name	City	State
Canada	Libin Cardiovascular Institute of Alberta	Calgary	Alberta
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	QEII Health Sciences Center	Halifax	Nova Scotia
Canada	Hamilton Health Sciences Centre	Hamilton	Ontario
Canada	London Health Sciences Centre	London	Ontario
Canada	Centre Hospitalier de l"Universite de Montreal-Hotel Dieu	Montreal	Quebec
Canada	McGill University Health Centre	Montreal	Quebec
Canada	Montreal Heart Institute	Montreal	Quebec
Canada	Southlake Regional Health Centre	Newmarket	Ontario
Canada	University of Ottawa Heart Institute	Ottawa	Ontario
Canada	Prairie Vascular Research Inc-Regina General Hospital	Regina	Saskatchewan
Canada	Toronto General Hospital	Toronto	Ontario
Canada	St. Paul's Hospital	Vancouver	British Columbia
Japan	Hokkaido University	Sapporo

Sponsors (3)

Lead Sponsor	Collaborator
Ottawa Heart Institute Research Corporation	Canadian Institutes of Health Research (CIHR), Ontario Ministry of Health and Long Term Care

Countries where clinical trial is conducted

Canada,  Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinically Manifest Patients	"Clinically improved" if they are alive and not had a heart transplant and have not had heart failure hospitalization and no sustained VT/VF and meet one or more of following; (i) No sustained VT (if presented with sustained VT) (ii) Improvement in LV function (defined as 10% decrease in LV end systolic volume or 5% absolute increase in LVEF) (iii) Resolution of conduction system disease (if presented with sustained heart block); failure hospitalization and have not had sustained VT and one or both of: a. LV function improvement (defined as 10% decrease in LV end systolic volume) b. Resolution of conduction system disease.	On active therapy for 6 months
Primary	Clinically Silent and Control Patients	Cardiac death or cardiac transplantation or sustained VT/VF or sustained second or third degree AV block or development of clinical congestive heart failure (with documented LVEF < 50%).	9 years
Secondary	total mortality		6 months and 60 months
Secondary	cardiovascular mortality		6 months and 60 months
Secondary	heart failure hospitalization		6 months and 60 months
Secondary	change in LVEF from baseline		6 months and 60 months
Secondary	change in disease activity as assessed by PET imaging	comparing pre-treatment to 6 month scans	6 months and 60 months
Secondary	Atrial Fibrillation burden	from defibrillator diagnostics	6 months and 60 months
Secondary	Ventricular arrhythmia burden	from defibrillator diagnostics	6 months and 60 months
Secondary	% of ventricular pacing		6 months and 60 months