Cardiac Sarcoidosis Randomized Trial (CHASM-CS-RCT)
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|ClinicalTrials.gov Identifier: NCT03593759|
Recruitment Status : Recruiting
First Posted : July 20, 2018
Last Update Posted : April 12, 2021
Prospective randomized controlled trial comparing low dose Prednisone/Methotrexate combination to standard dose Prednisone in patients diagnosed with acute active clinically manifest cardiac sarcoidosis and not yet treated.
The Investigators hypothesize that low dose Prednisone/Methotrexate combination will be as effective as standard dose Prednisone, and result in significantly better quality of life and less toxicity than standard dose Prednisone.
|Condition or disease||Intervention/treatment||Phase|
|Cardiac Sarcoidosis Sarcoidosis||Drug: Prednisone Drug: Methotrexate||Phase 3|
Subjects meeting the study inclusion/exclusion criteria will be randomized equally to receive either:
- Prednisone 0.5 mg kg/day for 6-months (MAX dose 30 mg per day) or
- 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
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 (Clinical Trial)|
|Estimated Enrollment :||194 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Prospective, open-label, non-inferiority, randomized controlled with blinded end-point analysis.|
|Masking:||None (Open Label)|
|Official Title:||Cardiac Sarcoidosis Multi-Center Randomized Controlled Trial|
|Actual Study Start Date :||January 15, 2019|
|Estimated Primary Completion Date :||December 2023|
|Estimated Study Completion Date :||December 2024|
Active Comparator: Prednisone
Prednisone 0.5 mg kg/day for 6 months (max dose 30 mg)
Oral prednisone tablet
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.
Oral prednisone tablet
Oral, subcutaneous, or intramuscular methotrexate
- Summed perfusion rest score (SPRS) on FDG-PET scan [ Time Frame: 6 months ]Measure of myocardial scarring and fibrosis (blinded core lab analysis)
- Mortality [ Time Frame: 6 months ]All cause deaths
- Cardiovascular hospitalizations [ Time Frame: 6 months ]Cardiovascular related only
- Medication related adverse events [ Time Frame: 6 months ]Using clinical assessment, medication side-effect and adverse event reporting
- 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)
- Glucocorticoid Toxicity Index [ Time Frame: 6 months ]Composite scoring (improvement; no significant change; worsening) compared to baseline
- Patient reported symptoms related to medication [ Time Frame: 6 months ]Using medication side-effect questionnaire ( symptom present, yes or no; frequency; intensity)
- Medication compliance [ Time Frame: 6 months ]% of days where treatment was taken as prescribed
- Generic Quality of Life (SF 36) [ Time Frame: 6 months ]Measuring general QOL using SF-36 questionnaire
- Disease Specific Quality of Life (KSQ and SAT) [ Time Frame: 6 months ]Using Kings Sarcoidosis questionnaire and Sarcoidosis Assessment Tool
- BMI [ Time Frame: 6 months ]Weight and height combined to report BMI in kg/m2, absolute and delta compared to baseline
- Blood pressure [ Time Frame: 6 months ]Systolic and diastolic, absolute and delta compared to baseline
- HbA1C [ Time Frame: 6 months ]Absolute and delta compared to baseline
- T-score on bone density scan [ Time Frame: 6 months ]Absolute and delta compared to baseline
- FDG-PET and myocardial perfusion [ Time Frame: 6 month scan ]SPRS in mismatched segments; SUVmax, SUVmean and COI; LVEF, RVEF; whole body disease activity
- Ventricular arrhythmia burden [ Time Frame: 6 months ]Episodes of sustained ventricular arrhythmia or episodes requiring appropriate ICD therapy (shock or anti-tachycardia pacing)
- Complete heart block [ Time Frame: 6 months ]Percentage of patients who are in CHB
- LVEF and RVEF assessed on echocardiogram [ Time Frame: 6 months ]Ejection fraction, absolute and delta compared to baseline
- Highly sensitive Troponin I levels and BNP levels [ Time Frame: 6 months ]Absolute and delta compared to baseline
- CMR Endpoints [ Time Frame: 6 months ]Volume of delayed enhancement
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): NCT03593759
|Contact: David H Birnie, MDfirstname.lastname@example.org|
|Contact: Karen MacDonald, RN||613-696-7000 ext email@example.com|
|Principal Investigator:||David H Birnie, MD||Ottawa Heart Institute Research Corporation|