NCT03593759

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).

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
194

participants targeted

Target at P25-P50 for phase_3

Timeline
7mo left

Started Jan 2019

Longer than P75 for phase_3

Geographic Reach
4 countries

30 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress93%
Jan 2019Dec 2026

First Submitted

Initial submission to the registry

June 27, 2018

Completed
23 days until next milestone

First Posted

Study publicly available on registry

July 20, 2018

Completed
6 months until next milestone

Study Start

First participant enrolled

January 15, 2019

Completed
7.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2026

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2026

Last Updated

May 5, 2026

Status Verified

April 1, 2026

Enrollment Period

7.9 years

First QC Date

June 27, 2018

Last Update Submit

April 29, 2026

Conditions

Keywords

Cardiac SarcoidosisPrednisone (or Prednisolone)Methotrexate

Outcome Measures

Primary Outcomes (1)

  • Summed perfusion rest score (SPRS) on FDG-PET scan

    Measure of myocardial scarring and fibrosis (blinded core lab analysis)

    6 months

Secondary Outcomes (19)

  • Mortality

    6 months

  • Cardiovascular hospitalizations

    6 months

  • Medication related adverse events

    6 months

  • Modified Cleveland Clinic Glucocorticoid Toxicity Score

    6 months

  • Glucocorticoid Toxicity Index

    6 months

  • +14 more secondary outcomes

Study Arms (2)

Prednisone (or Prednisolone)

ACTIVE COMPARATOR

\[Dose everywhere except Japan\] 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

Methotrexate

EXPERIMENTAL

\[Dose everywhere except Japan\] 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.

Drug: Prednisone or PrednisoloneDrug: Methotrexate

Interventions

Oral prednisone/prednisolone tablet

MethotrexatePrednisone (or Prednisolone)

Oral, subcutaneous, or intramuscular methotrexate

Methotrexate

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • (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

You may not qualify if:

  • Current or recent (within two months) non-topical treatment for sarcoidosis
  • Current Oral/IV treatment of duration greater than 5 days
  • Currently taking Methotrexate or Prednisone for another health condition
  • Intolerance or contra-indication to Methotrexate or Prednisone
  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (30)

Yale-New Haven Hospital

New Haven, Connecticut, 06520, United States

RECRUITING

Tufts Medical Center

Boston, Massachusetts, 02111, United States

RECRUITING

University of Michigan-Michigan Medicine Cardiovascular Center

Ann Arbor, Michigan, 48109-5853, United States

RECRUITING

University of Minnesota

Minneota, Minnesota, 55455, United States

NOT YET RECRUITING

Montefiore Medical Center

New York, New York, 10467, United States

RECRUITING

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

RECRUITING

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

RECRUITING

University of Utah

Salt Lake City, Utah, 84112, United States

RECRUITING

Virginia Commonwealth University

Richmond, Virginia, 23298-0053, United States

RECRUITING

Libin Cardiovascular Institute of Alberta

Calgary, Alberta, T2N 2T9, Canada

RECRUITING

St. Paul's Hospital

Vancouver, British Columbia, V5Z 1M9, Canada

RECRUITING

Eastern Health Health Sciences Centre

St. John's, Newfoundland and Labrador, A1B 3V6, Canada

RECRUITING

QE II Health Sciences Centre

Halifax, Nova Scotia, B3H 3A7, Canada

RECRUITING

St. Joseph's Healthcare Centre

Hamilton, Ontario, L8N 4A6, Canada

RECRUITING

London Health Sciences Centre

London, Ontario, N6A 4A5, Canada

RECRUITING

University of Ottawa Heart Institute

Ottawa, Ontario, K1Y 4W7, Canada

RECRUITING

Montreal Heart Institute

Montreal, Quebec, H1T 1C8, Canada

RECRUITING

CIUSSS-Hopital du Sacre-Coeur de Montreal

Montreal, Quebec, H4J 1C5, Canada

RECRUITING

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

Québec, Quebec, G1V 4G5, Canada

RECRUITING

CIUSSS de l'Estrie - CHUS - Hôpital Fleurimont

Sherbrooke, Quebec, J1H 5N4, Canada

RECRUITING

Hokkaido University

Sapporo, Kita 8, Nishi 5, Kita-Ku, 060-0808, Japan

RECRUITING

Chiba University

Chiba, Japan

RECRUITING

University of Fukui

Fukui, Japan

NOT YET RECRUITING

St. Marrianna University

Kawasaki, Japan

NOT YET RECRUITING

Nagoya City University

Nagoya, Japan

RECRUITING

National Cerebral and Cardiovascular Center (NCVC)

Osaka, Japan

RECRUITING

Sapporo Medical University

Sapporo, Japan

RECRUITING

Nippon Medical School

Tokyo, Japan

RECRUITING

King's College Hospital NHS Foundation Trust

London, SE5 9RS, United Kingdom

NOT YET RECRUITING

Imperial College Healthcare Trust-NHS-Hammersmith Hospital

London, W12 0HS, United Kingdom

NOT YET RECRUITING

Related Publications (1)

  • 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.

MeSH Terms

Conditions

Sarcoidosis

Interventions

PrednisonePrednisoloneMethotrexate

Condition Hierarchy (Ancestors)

Lymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesHypersensitivity, DelayedHypersensitivityImmune System Diseases

Intervention Hierarchy (Ancestors)

PregnadienediolsPregnadienesPregnanesSteroidsFused-Ring CompoundsPolycyclic CompoundsPregnadienetriolsAminopterinPterinsPteridinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Study Officials

  • David H Birnie, MD

    Ottawa Heart Institute Research Corporation

    PRINCIPAL INVESTIGATOR

Central Study Contacts

David H Birnie, MD

CONTACT

Janine Ryan, BAH, CCRP

CONTACT

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Prospective, open-label, non-inferiority, randomized controlled with blinded end-point analysis.
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 27, 2018

First Posted

July 20, 2018

Study Start

January 15, 2019

Primary Completion (Estimated)

December 1, 2026

Study Completion (Estimated)

December 1, 2026

Last Updated

May 5, 2026

Record last verified: 2026-04

Data Sharing

IPD Sharing
Will not share

Locations