Clinical trial NCT01477359: Cardiac Sarcoidosis Multi-Center Prospective Cohort
Official title: Cardiac Sarcoidosis Multi-Center Prospective Cohort Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Cardiac Sarcoidosis
Keywords: Sarcoidosis
Lead sponsor: Ottawa Heart Institute Research Corporation
Sponsor class: OTHER
Collaborators: name: Ontario Ministry of Health and Long Term Care
name: Canadian Institutes of Health Research (CIHR)
First posted: 2011-11-22
Enrollment: 1500
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Electrophysiology Service patients

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Clinically Manifest Patients
timeFrame: On active therapy for 6 months
measure: Clinically Silent and Control Patients
timeFrame: 9 years
Secondary outcomes:
measure: total mortality
timeFrame: 6 months and 60 months
measure: cardiovascular mortality
timeFrame: 6 months and 60 months
measure: heart failure hospitalization
timeFrame: 6 months and 60 months
measure: change in LVEF from baseline
timeFrame: 6 months and 60 months
measure: change in disease activity as assessed by PET imaging
timeFrame: 6 months and 60 months
measure: Atrial Fibrillation burden
timeFrame: 6 months and 60 months
measure: Ventricular arrhythmia burden
timeFrame: 6 months and 60 months
measure: % of ventricular pacing
timeFrame: 6 months and 60 months
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Libin Cardiovascular Institute of Alberta
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Vancouver
country: Canada
facility: St. Paul's Hospital
state: British Columbia
city: Halifax
country: Canada
facility: QEII Health Sciences Center
state: Nova Scotia
city: Hamilton
country: Canada
facility: Hamilton Health Sciences Centre
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Newmarket
country: Canada
facility: Southlake Regional Health Centre
state: Ontario
city: Ottawa
country: Canada
facility: University of Ottawa Heart Institute
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Montreal
country: Canada
facility: Montreal Heart Institute
state: Quebec
city: Montreal
country: Canada
facility: Centre Hospitalier de l"Universite de Montreal-Hotel Dieu
state: Quebec
city: Montreal
country: Canada
facility: McGill University Health Centre
state: Quebec
city: Regina
country: Canada
facility: Prairie Vascular Research Inc-Regina General Hospital
state: Saskatchewan
city: Sapporo
country: Japan
facility: Hokkaido University
Study officials:
affiliation: Ottawa Heart Institute Research Corporation
name: David Birnie, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ottawa Heart Institute Research Corporation
name: Pablo Nery, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ottawa Heart Institute Research Corporation
name: Rob Beanlands, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Weng W, Wiefels C, Chakrabarti S, Nery PB, Celiker-Guler E, Healey JS, Hruczkowski TW, Quinn FR, Promislow S, Medor MC, Spence S, Odabashian R, Alqarawi W, Juneau D, de Kemp R, Leung E, Beanlands R, Birnie D. Atrial Arrhythmias in Clinically Manifest Cardiac Sarcoidosis: Incidence, Burden, Predictors, and Outcomes. J Am Heart Assoc. 2020 Sep;9(17):e017086. doi: 10.1161/JAHA.120.017086. Epub 2020 Aug 20.
citation: Martineau P, Pelletier-Galarneau M, Juneau D, Leung E, Nery PB, de Kemp R, Beanlands R, Birnie D. Imaging Cardiac Sarcoidosis With FLT-PET Compared With FDG/Perfusion-PET: A Prospective Pilot Study. JACC Cardiovasc Imaging. 2019 Nov;12(11 Pt 1):2280-2281. doi: 10.1016/j.jcmg.2019.06.020. Epub 2019 Aug 14. No abstract available.