Cardiac Sarcoidosis Randomized Trial

NCT ID: NCT03593759

Last Updated: 2024-12-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

194 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-01-15

Study Completion Date

2025-12-31

Brief Summary

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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).

Detailed Description

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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 OD (exact dose and directions at physician) 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 an optional 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, optional 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.

Conditions

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Cardiac Sarcoidosis Sarcoidosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Prospective, open-label, non-inferiority, randomized controlled with blinded end-point analysis.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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

Group Type ACTIVE_COMPARATOR

Prednisone or Prednisolone

Intervention Type DRUG

Oral prednisone/prednisolone tablet

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 OD (exact dose and directions at physicians discretion) 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.

Group Type EXPERIMENTAL

Prednisone or Prednisolone

Intervention Type DRUG

Oral prednisone/prednisolone tablet

Methotrexate

Intervention Type DRUG

Oral, subcutaneous, or intramuscular methotrexate

Interventions

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Prednisone or Prednisolone

Oral prednisone/prednisolone tablet

Intervention Type DRUG

Methotrexate

Oral, subcutaneous, or intramuscular methotrexate

Intervention Type DRUG

Eligibility Criteria

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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

6. Patient is unable or unwilling to provide informed consent
7. Patient is included in another randomized clinical trial
8. Patient has a contraindication to PET imaging or is unlikely to tolerate due to severe claustrophobia
9. Pregnancy (all women of child bearing age and potential will have a negative BHCG test before enrollment)
10. Breastfeeding
11. Women of childbearing age who refuse to use a highly effective and medically acceptable form of contraception throughout the study
12. Patients for whom the investigator believes that the trial is not in the interest of the patient

Exclusion Criteria

1. Current or recent (within two months) non-topical treatment for sarcoidosis
2. Current Oral/IV treatment of duration greater than 5 days
3. Currently taking Methotrexate or Prednisone for another health condition
4. Intolerance or contra-indication to Methotrexate or Prednisone
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role collaborator

Ottawa Heart Institute Research Corporation

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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David H Birnie, MD

Role: PRINCIPAL_INVESTIGATOR

Ottawa Heart Institute Research Corporation

Locations

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Yale-New Haven Hospital

New Haven, Connecticut, United States

Site Status RECRUITING

Tufts Medical Center

Boston, Massachusetts, United States

Site Status RECRUITING

University of Michigan-Michigan Medicine Cardiovascular Center

Ann Arbor, Michigan, United States

Site Status RECRUITING

University of Minnesota

Minneota, Minnesota, United States

Site Status NOT_YET_RECRUITING

Montefiore Medical Center

New York, New York, United States

Site Status RECRUITING

The Ohio State University Wexner Medical Center

Columbus, Ohio, United States

Site Status RECRUITING

Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

University of Utah

Salt Lake City, Utah, United States

Site Status RECRUITING

Virginia Commonwealth University

Richmond, Virginia, United States

Site Status RECRUITING

Libin Cardiovascular Institute of Alberta

Calgary, Alberta, Canada

Site Status RECRUITING

St. Paul's Hospital

Vancouver, British Columbia, Canada

Site Status RECRUITING

Eastern Health Health Sciences Centre

St. John's, Newfoundland and Labrador, Canada

Site Status RECRUITING

QE II Health Sciences Centre

Halifax, Nova Scotia, Canada

Site Status RECRUITING

St. Joseph's Healthcare Centre

Hamilton, Ontario, Canada

Site Status RECRUITING

London Health Sciences Centre

London, Ontario, Canada

Site Status RECRUITING

University of Ottawa Heart Institute

Ottawa, Ontario, Canada

Site Status RECRUITING

Montreal Heart Institute

Montreal, Quebec, Canada

Site Status RECRUITING

CIUSSS-Hopital du Sacre-Coeur de Montreal

Montreal, Quebec, Canada

Site Status RECRUITING

Institut universitaire de cardiologie et de pneumologie de Québec-Université Laval

Québec, Quebec, Canada

Site Status RECRUITING

CIUSSS de l'Estrie - CHUS - Hôpital Fleurimont

Sherbrooke, Quebec, Canada

Site Status RECRUITING

Hokkaido University

Sapporo, Kita 8, Nishi 5, Kita-Ku, Japan

Site Status RECRUITING

Chiba University

Chiba, , Japan

Site Status RECRUITING

University of Fukui

Fukui, , Japan

Site Status NOT_YET_RECRUITING

St. Marrianna University

Kawasaki, , Japan

Site Status NOT_YET_RECRUITING

Nagoya City University

Nagoya, , Japan

Site Status RECRUITING

National Cerebral and Cardiovascular Center (NCVC)

Osaka, , Japan

Site Status RECRUITING

Sapporo Medical University

Sapporo, , Japan

Site Status RECRUITING

Nippon Medical School

Tokyo, , Japan

Site Status RECRUITING

King's College Hospital NHS Foundation Trust

London, , United Kingdom

Site Status NOT_YET_RECRUITING

Imperial College Healthcare Trust-NHS-Hammersmith Hospital

London, , United Kingdom

Site Status NOT_YET_RECRUITING

Countries

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United States Canada Japan United Kingdom

Central Contacts

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David H Birnie, MD

Role: CONTACT

613-696-7269

Janine Ryan, BAH, CCRP

Role: CONTACT

613-696-7000 ext. 17077

Facility Contacts

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Edward Miller, MD

Role: primary

203-737-8871

Edward Miller, MD

Role: backup

Mili Mehta, MD

Role: primary

Amanda Vest, MD

Role: backup

Todd Koelling, MD

Role: primary

734-936-5265

Todd Koelling, MD

Role: backup

C Shenoy, MD

Role: primary

Yogita Rochlani, MD

Role: primary

Yogita Rochlani, MD

Role: backup

Steven Kalbfleisch, MD

Role: primary

Steven Kalbfleisch, MD

Role: backup

Indu Poornima, MD

Role: primary

Indu Poornima, MD

Role: backup

Line Kemeyou, MD

Role: primary

Line Kemeyou, MD

Role: backup

Jordana Kron, MD

Role: primary

804-828-7565

Jordana Kron, MD

Role: backup

Russell Quinn, MD

Role: primary

403-220-5500

Russell Quinn, MD

Role: backup

Mustafa Toma, MD

Role: primary

604 806 9986

Mustafa Toma, MD

Role: backup

Stephen Duffett, MD

Role: primary

709-777-6917

Stephen Duffett, MD

Role: backup

Doug Hayami, MD

Role: primary

Doug Hayami, MD

Role: backup

Nathan Hambly, MD

Role: primary

905-521-6183

Nathan Hambly, MD

Role: backup

Nikolaos Tzemos, MD

Role: primary

519-663-3038

Nikolaos Tzemos, MD

Role: backup

David H Birnie, MD

Role: primary

613-696-7269

David Birnie, MD

Role: backup

Genevieve Giraldeau, MD

Role: primary

514-376-3330 ext. 3858

Genevieve Giraldeau, MD

Role: backup

Leila Laroussi, MD

Role: primary

514-338-2050

Leila Laroussi, MD

Role: backup

Mario Senechal, MD

Role: primary

Mario Senechal, MD

Role: backup

Felix Ayala-Paredes, MD

Role: primary

819-346-1110 ext. 16317

Felix Ayala-Paredes, MD

Role: backup

Toshiyuki Nagai, MD

Role: primary

Toshiyuki Nagai, MD

Role: backup

Y Koboyashi, MD

Role: primary

Y Koboyashi

Role: backup

H Tada, MD

Role: primary

Y. Akashi, MD

Role: primary

Y Akashi, MD

Role: backup

K Nakasuka, MD

Role: primary

K Nakasuka, MD

Role: backup

Kengo Kusano, MD

Role: primary

Kengo Kusano, MD

Role: backup

Toshiyuki Yano, MD

Role: primary

Toshiyuki Yano, MD

Role: backup

Kenji Yodogawa, MD

Role: primary

Kenji Yodagawa, MD

Role: backup

Francis D Murgatroyd, MD

Role: primary

+44 (0)20 32993217

Francis D Murgatroyd, MD

Role: backup

Amanda Varnava, MD

Role: primary

Amanda Varnava, MD

Role: backup

References

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Birnie D, Beanlands RSB, Nery P, Aaron SD, Culver DA, DeKemp RA, Gula L, Ha A, Healey JS, Inoue Y, Judson MA, Juneau D, Kusano K, Quinn R, Rivard L, Toma M, Varnava A, Wells G, Wickremasinghe M, Kron J. Cardiac Sarcoidosis multi-center randomized controlled trial (CHASM CS- RCT). Am Heart J. 2020 Feb;220:246-252. doi: 10.1016/j.ahj.2019.10.003. Epub 2019 Oct 20.

Reference Type DERIVED
PMID: 31911261 (View on PubMed)

Other Identifiers

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UOttawaHI

Identifier Type: -

Identifier Source: org_study_id