Cardiac Sarcoidosis Randomized Trial (CHASM-CS-RCT)

July 24, 2023 updated by: Ottawa Heart Institute Research Corporation

Cardiac Sarcoidosis Multi-Center Randomized Controlled Trial

Prospective randomized controlled trial comparing low dose Prednisone(or Prednisolone)/Methotrexate combination to standard dose Prednisone(or Prednisolone) in patients diagnosed with acute active clinically manifest cardiac sarcoidosis and not yet treated.

The Investigators hypothesize that low dose Prednisone(or Prednisolone)/Methotrexate combination will be as effective as standard dose Prednisone(or Prednisolone), and result in significantly better quality of life and less toxicity than standard dose Prednisone(or Prednisolone).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Subjects meeting the study inclusion/exclusion criteria will be randomized equally to receive either:

Everywhere but Japan:

  1. Prednisone 0.5 mg kg/day for 6-months (MAX dose 30 mg per day) or
  2. Methotrexate 15-20 mg po, sc, or IM once a week for 6-months + Folic Acid 2 mg OD for 6 months + Prednisone 20 mg day for 1 month, then 10 mg OD for 1 month, then 5 mg OD for one month then STOP

In Japan:

  1. Prednisone or prednisolone 0.5 mg/kg po (max 30mg) for one month then reduce by 5 mg per month for five months or
  2. Methotrexate 5-20mg po, sc or IM once week for 6-months +Folic Acid 2-5 mg OD for 6-months+Prednisone or prednisolone 20mg OD for 1 month then 10mg OD for 1 month then 5 mg OD one month

Methotrexate will be initiated at a dose of 15 mg once a week and increased to 20 mg once a week after 4 weeks if tolerated. In case of Methotrexate-induced side-effects general guidelines will be provided, however specific management will be left to the treating physicians. Folic acid will be taken to help reduce methotrexate side-effects.

Prior to randomization and study treatment all subjects will have the following baseline tests done: baseline safety blood work; FDG-PET scan with myocardial perfusion imaging; ECG; echo; and a bone mineral density scan. Cardiac MRI (CMR) is optional but strongly encouraged. Blood will be obtained for biomarker core-lab analysis. Biomarkers to be assayed will include highly sensitive Troponin I. Samples will be stored for future novel biomarker discovery. Quality of LIfe (QOL) questionnaires (KSQ, SAT and SF-36) will be completed prior to treatment start.

After therapy initiation subjects will be seen at 4 weeks, 8 weeks (methotrexate arm only), and 12 weeks, with a final visit at 6 months. Safety bloodwork and assessment for medication side effects, using a medication side-effect questionnaire, will be completed at all visits. At 12 weeks QOL questionnaires will be completed. The primary endpoint will be assessed at 6-months, when FDG-PET with myocardial perfusion imaging, ECG, echo, bone mineral density scan, QOL questionnaires, blood for biomarkers and device interrogation will be done. CMR may be repeated. Skin, muscle strength testing and neuropsychiatric assessment will be completed at 6 months as part of the composite glucocorticoid toxicity index.

After the 6 month visit. further management will be at the treating physician's discretion. Details of the physicians planned treatment following the 6-month PET scan will be collected.

Standardized protocols for all aspects of FDG-PET scans (i.e. patient preparation, image acquisition, image processing, transfer to the core lab and analysis at core lab) will be followed.

Study Type

Interventional

Enrollment (Estimated)

194

Phase

  • Phase 3

Contacts and Locations

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

Study Contact

Study Contact Backup

Study Locations

  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 2T9
        • Recruiting
        • Libin Cardiovascular Institute of Alberta
        • Contact:
        • Principal Investigator:
          • Russell Quinn, MD
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 1M9
        • Not yet recruiting
        • St. Paul's Hospital
        • Contact:
        • Principal Investigator:
          • Mustafa Toma, MD
    • Newfoundland and Labrador
      • St. John's, Newfoundland and Labrador, Canada, A1B 3V6
        • Recruiting
        • Eastern Health Health Sciences Centre
        • Contact:
        • Principal Investigator:
          • Stephen Duffett, MD
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3H 3A7
        • Recruiting
        • QE II Health Sciences Centre
        • Contact:
        • Principal Investigator:
          • Doug Hayami, MD
    • Ontario
      • Hamilton, Ontario, Canada, L8N 4A6
        • Recruiting
        • St. Joseph's Healthcare Centre
        • Contact:
        • Principal Investigator:
          • Nathan Hambly, MD
      • London, Ontario, Canada, N6A 4A5
        • Recruiting
        • London Health Sciences Centre
        • Contact:
        • Principal Investigator:
          • Nikolaos Tzemos, MD
      • Ottawa, Ontario, Canada, K1Y 4W7
        • Recruiting
        • University of Ottawa Heart Institute
        • Contact:
        • Principal Investigator:
          • David Birnie, MD
      • Toronto, Ontario, Canada, M5G 2C4
        • Not yet recruiting
        • University Health Network
        • Contact:
        • Principal Investigator:
          • Andrew Ha, MD
    • Quebec
      • Montreal, Quebec, Canada, H1T 1C8
        • Recruiting
        • Montreal Heart Institute
        • Contact:
        • Principal Investigator:
          • Genevieve Giraldeau, MD
      • Montreal, Quebec, Canada, H4J 1C5
        • Recruiting
        • CIUSSS-Hopital du Sacre-Coeur de Montreal
        • Contact:
        • Principal Investigator:
          • Leila Laroussi, MD
      • Quebec City, Quebec, Canada, G1V 4G5
        • Recruiting
        • Institut Universitaire de Cardiologie et de Pneumologie de Québec-Université Laval
        • Contact:
        • Principal Investigator:
          • Mario Senechal, MD
      • Sherbrooke, Quebec, Canada, J1H 5N4
        • Recruiting
        • CIUSSS de L'Estrie - CHUS - Hopital Fleurimont
        • Principal Investigator:
          • Félix Ayala-Paredes, MD
        • Contact:
  • Japan
      • Chiba, Japan
        • Recruiting
        • Chiba University
        • Contact:
          • Y Koboyashi, MD
        • Principal Investigator:
          • Y Koboyashi
      • Fukui, Japan
        • Not yet recruiting
        • University of Fukui
        • Contact:
          • H Tada, MD
        • Principal Investigator:
          • H Tada, MD
      • Kawasaki, Japan
        • Not yet recruiting
        • St. Marrianna University
        • Contact:
          • Y. Akashi, MD
        • Principal Investigator:
          • Y Akashi, MD
      • Nagoya, Japan
        • Recruiting
        • Nagoya City University
        • Contact:
        • Principal Investigator:
          • K Nakasuka, MD
      • Osaka, Japan
        • Recruiting
        • National Cerebral and Cardiovascular Center (NCVC)
        • Contact:
        • Principal Investigator:
          • Kengo Kusano, MD
      • Sapporo, Japan
        • Recruiting
        • Sapporo Medical University
        • Contact:
        • Principal Investigator:
          • Toshiyuki Yano, MD
      • Tokyo, Japan
        • Recruiting
        • Nippon Medical School
        • Contact:
        • Principal Investigator:
          • Kenji Yodagawa, MD
    • Kita 8, Nishi 5, Kita-Ku
      • Sapporo, Kita 8, Nishi 5, Kita-Ku, Japan, 060-0808
        • Recruiting
        • Hokkaido University
        • Contact:
        • Principal Investigator:
          • Toshiyuki Nagai, MD
  • United Kingdom
      • London, United Kingdom, SE5 9RS
        • Not yet recruiting
        • King's College Hospital NHS Foundation Trust
        • Contact:
        • Principal Investigator:
          • Francis D Murgatroyd, MD
      • London, United Kingdom, W12 0HS
        • Not yet recruiting
        • Imperial College Healthcare Trust-NHS-Hammersmith Hospital
        • Contact:
        • Principal Investigator:
          • Amanda Varnava, MD
  • United States
    • Connecticut
      • New Haven, Connecticut, United States, 06520
        • Recruiting
        • Yale-New Haven Hospital
        • Contact:
        • Principal Investigator:
          • Edward Miller, MD
    • Massachusetts
      • Boston, Massachusetts, United States, 02111
        • Recruiting
        • Tufts Medical Center
        • Contact:
          • Amanda Vest, MD
        • Principal Investigator:
          • Amanda Vest, MD
    • Michigan
      • Ann Arbor, Michigan, United States, 48109-5853
        • Recruiting
        • University of Michigan-Michigan Medicine Cardiovascular Center
        • Contact:
        • Principal Investigator:
          • Todd Koelling, MD
    • Minnesota
      • Minnesota, Minnesota, United States, 55455
        • Not yet recruiting
        • University of Minnesota
        • Contact:
          • C Shenoy, MD
        • Principal Investigator:
          • C Shenoy, MD
    • New York
      • New York, New York, United States, 10467
        • Recruiting
        • Montefiore Medical Center
        • Contact:
        • Principal Investigator:
          • Yogita Rochlani, MD
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • The Ohio State University Wexner Medical Center
        • Principal Investigator:
          • Steven Kalbfleisch, MD
        • Contact:
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15212
        • Not yet recruiting
        • Allegheny General Hospital
        • Principal Investigator:
          • Indu Poornima, MD
        • Contact:
          • Matthew Yeager
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Recruiting
        • University of Utah
        • Contact:
        • Principal Investigator:
          • Line Kemeyou, MD
    • Virginia
      • Richmond, Virginia, United States, 23298-0053
        • Recruiting
        • Virginia Commonwealth University
        • Contact:
        • Principal Investigator:
          • Jordana Kron, MD

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

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

(i) Cardiac sarcoidosis presenting with one or more of the following clinical findings:

  • advanced conduction system disease (defined as Mobitz II AV block or third degree AV block)
  • significant sinus node dysfunction (defined as average HR less than 40bpm when awake and/or sustained atrial arrhythmias)
  • non- sustained or sustained ventricular arrhythmia
  • left ventricular dysfunction (LVEF < 50%)
  • right ventricular dysfunction (RVEF < 40%)

AND

(ii) No alternative explanation for clinical features

AND

(iii) FDG-PET uptake suggestive of active CS within two months of enrollment AND Myocardial Perfusion Imaging (MPI) completed (confirmed by PET core lab read)

AND ONE OR BOTH OF FOLLOWING

(iv) Positive biopsy for Sarcoid (either EMB or extra-cardiac)

(v) CT Chest showing features consistent with pulmonary sarcoidosis and/or mediastinal and/or hilar lymphadenopathy

Exclusion Criteria:

  1. Current or recent (within two months) non-topical treatment for sarcoidosis
  2. Currently taking Methotrexate or Prednisone for another health condition
  3. Intolerance or contra-indication to Methotrexate or Prednisone
  4. Patient does not meet all of the above listed inclusion criteria
  5. Patient is unable or unwilling to provide informed consent
  6. Patient is included in another randomized clinical trial
  7. Patient has a contraindication to PET imaging or is unlikely to tolerate due to severe claustrophobia
  8. Pregnancy (all women of child bearing age and potential will have a negative BHCG test before enrollment)
  9. Breastfeeding
  10. Women of childbearing age who refuse to use a highly effective and medically acceptable form of contraception throughout the study
  11. Patients for whom the investigator believes that the trial is not in the interest of the patient

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

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Prednisone (or Prednisolone)

[Dose everywhere except Japan] Prednisone 0.5 mg kg/day for 6 months (max dose 30 mg)

[Dose in Japan] Prednisone or prednisolone 0.5 mg/kg po (max 30mg) for one month then reduce by 5 mg per month for five months
Drug: Prednisone or Prednisolone
Oral prednisone/prednisolone tablet
Experimental: Methotrexate

[Dose everywhere except Japan] Methotrexate 15-20 mg orally, sc, or IM once a week for 6 months + Prednisone 20 mg po daily for one month then 10 mg po daily for one month then 5 mg po daily for one month and then stop. Also Folic Acid 2 mg po daily for 6 months.

[Dose in Japan] Methotrexate 5-20mg mg orally, sc, or IM once a week for 6 months+ Prednisone or Prednisolone 20mg OD for 1 month then 10mg OD for 1 month then 5 mg OD one month. Also Folic Acid 2 mg po daily for 6 months.
Drug: Prednisone or Prednisolone
Oral prednisone/prednisolone tablet
Drug: Methotrexate
Oral, subcutaneous, or intramuscular methotrexate

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Summed perfusion rest score (SPRS) on FDG-PET scan
Time Frame: 6 months
Measure of myocardial scarring and fibrosis (blinded core lab analysis)
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mortality
Time Frame: 6 months
All cause deaths
6 months
Cardiovascular hospitalizations
Time Frame: 6 months
Cardiovascular related only
6 months
Medication related adverse events
Time Frame: 6 months
Using clinical assessment, medication side-effect and adverse event reporting
6 months
Modified Cleveland Clinic Glucocorticoid Toxicity Score
Time Frame: 6 months
Summed score of new/worsening diabetes;new/worsening HTN; osteoporosis; change in height and weight (combined and reported as BMI in kg/m2)
6 months
Glucocorticoid Toxicity Index
Time Frame: 6 months
Composite scoring (improvement; no significant change; worsening) compared to baseline
6 months
Patient reported symptoms related to medication
Time Frame: 6 months
Using medication side-effect questionnaire ( symptom present, yes or no; frequency; intensity)
6 months
Medication compliance
Time Frame: 6 months
% of days where treatment was taken as prescribed
6 months
Generic Quality of Life (SF 36)
Time Frame: 6 months
Measuring general QOL using SF-36 questionnaire
6 months
Disease Specific Quality of Life (KSQ and SAT)
Time Frame: 6 months
Using Kings Sarcoidosis questionnaire and Sarcoidosis Assessment Tool
6 months
BMI
Time Frame: 6 months
Weight and height combined to report BMI in kg/m2, absolute and delta compared to baseline
6 months
Blood pressure
Time Frame: 6 months
Systolic and diastolic, absolute and delta compared to baseline
6 months
HbA1C
Time Frame: 6 months
Absolute and delta compared to baseline
6 months
T-score on bone density scan
Time Frame: 6 months
Absolute and delta compared to baseline
6 months
FDG-PET and myocardial perfusion
Time Frame: 6 month scan
SPRS in mismatched segments; SUVmax, SUVmean and COI; LVEF, RVEF; whole body disease activity
6 month scan
Ventricular arrhythmia burden
Time Frame: 6 months
Episodes of sustained ventricular arrhythmia or episodes requiring appropriate ICD therapy (shock or anti-tachycardia pacing)
6 months
Complete heart block
Time Frame: 6 months
Percentage of patients who are in CHB
6 months
LVEF and RVEF assessed on echocardiogram
Time Frame: 6 months
Ejection fraction, absolute and delta compared to baseline
6 months
Highly sensitive Troponin I levels and BNP levels
Time Frame: 6 months
Absolute and delta compared to baseline
6 months
CMR Endpoints
Time Frame: 6 months
Volume of delayed enhancement
6 months

Collaborators and Investigators

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

Sponsor

Ottawa Heart Institute Research Corporation

Collaborators

Canadian Institutes of Health Research (CIHR)

Investigators

  • Principal Investigator: David H Birnie, MD, Ottawa Heart Institute Research Corporation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

January 15, 2019

Primary Completion (Estimated)

December 1, 2025

Study Completion (Estimated)

December 1, 2025

Study Registration Dates

First Submitted

June 27, 2018

First Submitted That Met QC Criteria

July 10, 2018

First Posted (Actual)

July 20, 2018

Study Record Updates

Last Update Posted (Actual)

July 25, 2023

Last Update Submitted That Met QC Criteria

July 24, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UOttawaHI

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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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