Brief Summary
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).
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).
Brief Title
Cardiac Sarcoidosis Randomized Trial
Detailed Description
Subjects meeting the study inclusion/exclusion criteria will be randomized equally to receive either:
Everywhere but Japan:
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
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 or
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.
Everywhere but Japan:
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
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 or
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.
Categories
Central Contacts
Central Contact Role
Contact
Central Contact Phone
613-696-7269
Central Contact Email
dbirnie@ottawaheart.ca
Central Contact Role
Contact
Central Contact Phone
613-696-7000
Central Contact Phone Ext
17077
Central Contact Email
jryan@ottawaheart.ca
Completion Date
Completion Date Type
Estimated
Conditions
Cardiac Sarcoidosis
Sarcoidosis
Eligibility Criteria
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 (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:
Current or recent (within two months) non-topical treatment for sarcoidosis
Currently taking Methotrexate or Prednisone for another health condition
Intolerance or contra-indication to Methotrexate or Prednisone
Patient does not meet all of the above listed inclusion criteria
Patient is unable or unwilling to provide informed consent
Patient is included in another randomized clinical trial
Patient has a contraindication to PET imaging or is unlikely to tolerate due to severe claustrophobia
Pregnancy (all women of child bearing age and potential will have a negative BHCG test before enrollment)
Breastfeeding
Women of childbearing age who refuse to use a highly effective and medically acceptable form of contraception throughout the study
Patients for whom the investigator believes that the trial is not in the interest of the patient
(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 (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:
Current or recent (within two months) non-topical treatment for sarcoidosis
Currently taking Methotrexate or Prednisone for another health condition
Intolerance or contra-indication to Methotrexate or Prednisone
Patient does not meet all of the above listed inclusion criteria
Patient is unable or unwilling to provide informed consent
Patient is included in another randomized clinical trial
Patient has a contraindication to PET imaging or is unlikely to tolerate due to severe claustrophobia
Pregnancy (all women of child bearing age and potential will have a negative BHCG test before enrollment)
Breastfeeding
Women of childbearing age who refuse to use a highly effective and medically acceptable form of contraception throughout the study
Patients for whom the investigator believes that the trial is not in the interest of the patient
Inclusion Criteria
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) Nuclear Imaging within six-months of enrollment consisting of FDG-PET scan with FDG uptake suggestive of active CS and myocardial perfusion imaging
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
(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) Nuclear Imaging within six-months of enrollment consisting of FDG-PET scan with FDG uptake suggestive of active CS and myocardial perfusion imaging
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
Gender
All
Gender Based
false
Keywords
Cardiac Sarcoidosis
Prednisone (or Prednisolone)
Methotrexate
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT03593759
Org Class
Other
Org Full Name
Ottawa Heart Institute Research Corporation
Org Study Id
UOttawaHI
Overall Status
Recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
Cardiac Sarcoidosis Multi-Center Randomized Controlled Trial
Primary Outcomes
Outcome Description
Measure of myocardial scarring and fibrosis (blinded core lab analysis)
Outcome Measure
Summed perfusion rest score (SPRS) on FDG-PET scan
Outcome Time Frame
6 months
Secondary Outcomes
Outcome Description
All cause deaths
Outcome Time Frame
6 months
Outcome Measure
Mortality
Outcome Description
Cardiovascular related only
Outcome Time Frame
6 months
Outcome Measure
Cardiovascular hospitalizations
Outcome Description
Using clinical assessment, medication side-effect and adverse event reporting
Outcome Time Frame
6 months
Outcome Measure
Medication related adverse events
Outcome Description
Summed score of new/worsening diabetes;new/worsening HTN; osteoporosis; change in height and weight (combined and reported as BMI in kg/m2)
Outcome Time Frame
6 months
Outcome Measure
Modified Cleveland Clinic Glucocorticoid Toxicity Score
Outcome Description
Composite scoring (improvement; no significant change; worsening) compared to baseline
Outcome Time Frame
6 months
Outcome Measure
Glucocorticoid Toxicity Index
Outcome Description
Using medication side-effect questionnaire ( symptom present, yes or no; frequency; intensity)
Outcome Time Frame
6 months
Outcome Measure
Patient reported symptoms related to medication
Outcome Description
% of days where treatment was taken as prescribed
Outcome Time Frame
6 months
Outcome Measure
Medication compliance
Outcome Description
Measuring general QOL using SF-36 questionnaire
Outcome Time Frame
6 months
Outcome Measure
Generic Quality of Life (SF 36)
Outcome Description
Using Kings Sarcoidosis questionnaire and Sarcoidosis Assessment Tool
Outcome Time Frame
6 months
Outcome Measure
Disease Specific Quality of Life (KSQ and SAT)
Outcome Description
Weight and height combined to report BMI in kg/m2, absolute and delta compared to baseline
Outcome Time Frame
6 months
Outcome Measure
BMI
Outcome Description
Systolic and diastolic, absolute and delta compared to baseline
Outcome Time Frame
6 months
Outcome Measure
Blood pressure
Outcome Description
Absolute and delta compared to baseline
Outcome Time Frame
6 months
Outcome Measure
HbA1C
Outcome Description
Absolute and delta compared to baseline
Outcome Time Frame
6 months
Outcome Measure
T-score on bone density scan
Outcome Description
SPRS in mismatched segments; SUVmax, SUVmean and COI; LVEF, RVEF; whole body disease activity
Outcome Time Frame
6 month scan
Outcome Measure
FDG-PET and myocardial perfusion
Outcome Description
Episodes of sustained ventricular arrhythmia or episodes requiring appropriate ICD therapy (shock or anti-tachycardia pacing)
Outcome Time Frame
6 months
Outcome Measure
Ventricular arrhythmia burden
Outcome Description
Percentage of patients who are in CHB
Outcome Time Frame
6 months
Outcome Measure
Complete heart block
Outcome Description
Ejection fraction, absolute and delta compared to baseline
Outcome Time Frame
6 months
Outcome Measure
LVEF and RVEF assessed on echocardiogram
Outcome Description
Absolute and delta compared to baseline
Outcome Time Frame
6 months
Outcome Measure
Highly sensitive Troponin I levels and BNP levels
Outcome Description
Volume of delayed enhancement
Outcome Time Frame
6 months
Outcome Measure
CMR Endpoints
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Locked Fields
Render the field
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Yogita Rochlani
Investigator Email
yrochlani@montefiore.org
Investigator Department
Medicine
Investigator Division
Cardiology
Investigator Sponsor Organization
External
Study Department
Medicine
Study Division
Cardiology
Categories Mesh Debug
Blood & Bone Marrow Cancers --- LYMPHOPROLIFERATIVE DISORDERS
Blood & Bone Marrow Cancers --- LYMPHATIC DISEASES
Lung --- HYPERSENSITIVITY
Infectious Disease --- IMMUNE SYSTEM DISEASES
Lung --- IMMUNE SYSTEM DISEASES
MeSH Terms
SARCOIDOSIS
LYMPHOPROLIFERATIVE DISORDERS
LYMPHATIC DISEASES
HEMIC AND LYMPHATIC DISEASES
HYPERSENSITIVITY, DELAYED
HYPERSENSITIVITY
IMMUNE SYSTEM DISEASES
PREDNISONE
PREDNISOLONE
METHOTREXATE
PREGNADIENEDIOLS
PREGNADIENES
PREGNANES
STEROIDS
FUSED-RING COMPOUNDS
POLYCYCLIC COMPOUNDS
PREGNADIENETRIOLS
AMINOPTERIN
PTERINS
PTERIDINES
HETEROCYCLIC COMPOUNDS, 2-RING
HETEROCYCLIC COMPOUNDS, FUSED-RING
HETEROCYCLIC COMPOUNDS