We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

Cardiac Sarcoidosis Multi-Center Prospective Cohort (CHASM-CS)

This study is currently recruiting participants.
Verified November 2017 by Ottawa Heart Institute Research Corporation
Sponsor:
ClinicalTrials.gov Identifier:
NCT01477359
First Posted: November 22, 2011
Last Update Posted: November 22, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborators:
Ontario Ministry of Health and Long Term Care
Canadian Institutes of Health Research (CIHR)
Information provided by (Responsible Party):
Ottawa Heart Institute Research Corporation
  Purpose

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.


Condition
Cardiac Sarcoidosis

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Cardiac Sarcoidosis Multi-Center Prospective Cohort Study

Resource links provided by NLM:


Further study details as provided by Ottawa Heart Institute Research Corporation:

Primary Outcome Measures:
  • Clinically Manifest Patients [ Time Frame: On active therapy for 6 months ]

    "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.


  • Clinically Silent and Control Patients [ Time Frame: 9 years ]
    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%).


Secondary Outcome Measures:
  • total mortality [ Time Frame: 6 months and 60 months ]
  • cardiovascular mortality [ Time Frame: 6 months and 60 months ]
  • heart failure hospitalization [ Time Frame: 6 months and 60 months ]
  • change in LVEF from baseline [ Time Frame: 6 months and 60 months ]
  • change in disease activity as assessed by PET imaging [ Time Frame: 6 months and 60 months ]
    comparing pre-treatment to 6 month scans

  • Atrial Fibrillation burden [ Time Frame: 6 months and 60 months ]
    from defibrillator diagnostics

  • Ventricular arrhythmia burden [ Time Frame: 6 months and 60 months ]
    from defibrillator diagnostics

  • % of ventricular pacing [ Time Frame: 6 months and 60 months ]

Biospecimen Retention:   Samples With DNA
Frozen plasma, serum and buffy coat.

Estimated Enrollment: 1500
Study Start Date: August 2012
Estimated Study Completion Date: December 2025
Estimated Primary Completion Date: December 2025 (Final data collection date for primary outcome measure)
Groups/Cohorts
CS screened as underlying etiology
  1. Patients with active Clinically Manifest CS
  2. Patients diagnosed with extra-cardiac sarcoidosis and being screened for CS

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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 99 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Electrophysiology Service patients
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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01477359


Contacts
Contact: Karen MacDonald, RN, BPE 613-696-7000 ext 17077 kmacdonald@ottawaheart.ca
Contact: David Birnie, MD 613-696-7269 dbirnie@ottawaheart.ca

Locations
Canada, Alberta
Libin Cardiovascular Institute of Alberta Recruiting
Calgary, Alberta, Canada, T2N 2T9
Contact: Russell Quinn, MD         
Principal Investigator: Russell Quinn, MD         
University of Alberta Hospital Recruiting
Edmonton, Alberta, Canada, T6G 2B7
Contact: Tomascz Hruczkowski, MD         
Principal Investigator: Tomascz Hruczkowski, MD         
Canada, British Columbia
St. Paul's Hospital Recruiting
Vancouver, British Columbia, Canada, V5Z 1M9
Contact: Shanta Chakrabarti, MD         
Principal Investigator: Shanta Chakrabarti, MD         
Canada, Ontario
Hamilton Health Sciences Centre Recruiting
Hamilton, Ontario, Canada, L8L 2X2
Contact: Jeff Healey, MD         
Contact: Gerard Cox, MD         
Principal Investigator: Jeff Healey, MD         
London Health Sciences Centre Recruiting
London, Ontario, Canada, N6A 5A5
Contact: Lorne Gula, MD         
Principal Investigator: Lorne Gula, MD         
University of Ottawa Heart Institute Recruiting
Ottawa, Ontario, Canada, K1Y 4W7
Contact: Karen MacDonald, RN BPE    613-696-7000 ext 17077    kmacdonald@ottawaheart.ca   
Contact: Tammy Knight    613-696-7000 ext 19080    tknight@ottawaheart.ca   
Principal Investigator: Pablo Nery, MD         
St. Michael's Hospital Recruiting
Toronto, Ontario, Canada, M5B 1W8
Contact: Paul Dorian, MD         
Principal Investigator: Paul Dorian, MD         
Toronto General Hospital Recruiting
Toronto, Ontario, Canada, M5G 2C4
Contact: Andrew Ha, MD         
Principal Investigator: Andrew Ha, MD         
Canada, Quebec
Montreal Heart Institute Recruiting
Montreal, Quebec, Canada, H1T 1C8
Contact: Mario Talajic, MD         
Principal Investigator: Mario Talajic, MD         
Centre Hospitalier de l"Universite de Montreal-Hotel Dieu Not yet recruiting
Montreal, Quebec, Canada, H2W 1T8
Contact: Julie Fleury, RN         
Principal Investigator: Benoit Coutu, MD         
McGill University Health Centre Not yet recruiting
Montreal, Quebec, Canada, H3G 1A4
Contact: Fiorella Rafti         
Principal Investigator: Vidal Essebag, MD         
Japan
Hokkaido University Graduate School of Medicine Recruiting
Sapporo, Japan
Contact: Hiroshi Ohira, MD         
Principal Investigator: Hiroshi Ohira, MD         
Sponsors and Collaborators
Ottawa Heart Institute Research Corporation
Ontario Ministry of Health and Long Term Care
Canadian Institutes of Health Research (CIHR)
Investigators
Principal Investigator: David Birnie, MD Ottawa Heart Institute Research Corporation
Principal Investigator: Pablo Nery, MD Ottawa Heart Institute Research Corporation
Principal Investigator: Rob Beanlands, MD Ottawa Heart Institute Research Corporation
  More Information

Responsible Party: Ottawa Heart Institute Research Corporation
ClinicalTrials.gov Identifier: NCT01477359     History of Changes
Other Study ID Numbers: UOHI-04
First Submitted: November 10, 2011
First Posted: November 22, 2011
Last Update Posted: November 22, 2017
Last Verified: November 2017

Keywords provided by Ottawa Heart Institute Research Corporation:
Sarcoidosis

Additional relevant MeSH terms:
Sarcoidosis
Lymphoproliferative Disorders
Lymphatic Diseases