Effectiveness of Methotrexate Versus Prednisone as First-line Therapy for Pulmonary Sarcoidosis

NCT04314193 | Active Not Recruiting Phase 4

• 1 other identifier: NL71782.078.19
• Study Type: interventional
• Target: 138
• Locations: 1 country
• Sites: 17

Brief Summary

This is a prospective, randomized, non-blinded, multi-center, non-inferiority trial designed to compare effectiveness and side-effects of methotrexate versus prednisone as first-line therapy for pulmonary sarcoidosis.

Conditions

Sarcoidosis, Pulmonary

Keywords

sarcoidosis; pulmonary; prednisone; methotrexate

Outcome Measures

Primary Outcomes (1)

• Forced Vital Capacity (FVC)

  Change in hospital-measured FVC between baseline and 24 weeks

  24 weeks after inclusion

Secondary Outcomes (79)

• Forced Vital Capacity (FVC)

  4 weeks

• Forced Vital Capacity (FVC)

  16 weeks

• Time to major pulmonary improvement measured by FVC

  24 weeks

• Change in FVC

  4 weeks

• Change in FVC

  16 weeks

Study Arms (2)

methotrexate

EXPERIMENTAL

Drug: Methotrexate

prednisone

ACTIVE COMPARATOR

Drug: Prednisone

Interventions

Methotrexate DRUG

Oral methotrexate (15 mg weekly to be increased to 25 mg weekly) for 24 weeks.

methotrexate

Prednisone DRUG

Oral prednisone (start 40 mg daily, to be tapered to 10 mg daily) for 24 weeks.

prednisone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of sarcoidosis according to the ATS/ERS/WASOG criteria, in case of absent histology a diagnosis of sarcoidosis can also be established in a multidisciplinary team meeting in a sarcoidosis expert center based on a highly suggestive clinical and radiological picture.
• Age ≥18 years.
• A forced vital capacity (FVC) of ≤90% of predicted, or a diffusion capacity of the lung for carbon monoxide (DLCO) ≤70% of predicted, or ≥5% FVC absolute decline/≥10% DLCO absolute decline in the past year. For pulmonary functions tests GLI reference values are used.

You may not qualify if:

• Any condition or circumstance that, in the opinion of the investigator, may make a subject unlikely or unable to complete the study or comply with study procedures.
• Previous immunosuppressive treatment for sarcoidosis
• Use of systemic immunosuppressive therapy within the preceding three months for another disease than sarcoidosis
• Pregnant, breastfeeding, or planning to become pregnant or breastfeed during the study treatment or within 90 days after the last dose in the randomized study phase. For males; planning to pro-create during the study or within 90 days after the last dose of the randomized study phase.
• Primary systemic treatment indication being an extra pulmonary location of sarcoidosis (e.g. cardiac of neurological)
• Contra-indication for methotrexate or corticosteroids:
• severely impaired renal function (creatinine clearance \<30 ml/min)
• impaired hepatic function (serum bilirubin-value \>5 mg/dl or 85,5 micromole/l)
• bone marrow insufficiency with severe leukopenia, thrombocytopenia, or anaemia
• severe acute or chronic infections, such as tuberculosis, HIV, parasitic infections or other immunodeficiency syndromes
• mouth, stomach or duodenal ulcers

Sponsors & Collaborators

• Erasmus Medical Center: lead
• St. Antonius Hospital: collaborator
• Longfonds: collaborator

Study Sites (17)

Jeroen Bosch Ziekenhuis

's-Hertogenbosch, 5223 GZ, Netherlands

Location

Vrije Universiteit Medisch Centrum

Amsterdam, 1007 MB, Netherlands

Location

Onze Lieve Vrouwe Gasthuis

Amsterdam, 1061 AC, Netherlands

Location

Academisch Medisch Centrum

Amsterdam, 1105 AZ, Netherlands

Location

Rijnstate Ziekenhuis

Arnhem, 6815 AD, Netherlands

Location

Amphia hospital

Breda, Netherlands

Location

Catharina Ziekenhuis

Eindhoven, Netherlands

Location

Medisch Spectrum Twente

Enschede, 7512 KZ, Netherlands

Location

Martini Ziekenhuis

Groningen, 9728 NT, Netherlands

Location

Zuyderland Medisch Centrum

Heerlen, 6419 PC, Netherlands

Location

Medical Center Leeuwarden

Leeuwarden, Netherlands

Location

Leids Universitair Medisch Centrum

Leiden, 2333 ZA, Netherlands

Location

Haaglanden Medisch Centrum

Leidschendam, 2262 BA, Netherlands

Location

Sint Antonius Ziekenhuis

Nieuwegein, 3425 CM, Netherlands

Location

Erasmus MC

Rotterdam, 3000 CA, Netherlands

Location

VieCuri Medical Center

Venlo, Netherlands

Location

Isala Klinieken

Zwolle, 8025 AB, Netherlands

Location

Related Publications (2)

• Kahlmann V, Janssen Bonas M, Moor CC, Grutters JC, Mostard RLM, van Rijswijk HNAJ, van der Maten J, Marges ER, Moonen LAA, Overbeek MJ, Koopman B, Loth DW, Nossent EJ, Wagenaar M, Kramer H, Wielders PLML, Bonta PI, Walen S, Bogaarts BAHA, Kerstens R, Overgaauw M, Veltkamp M, Wijsenbeek MS; PREDMETH Collaborators. First-Line Treatment of Pulmonary Sarcoidosis with Prednisone or Methotrexate. N Engl J Med. 2025 Jul 17;393(3):231-242. doi: 10.1056/NEJMoa2501443. Epub 2025 May 18.

  PMID: 40387020 DERIVED

• Kahlmann V, Janssen Bonas M, Moor CC, van Moorsel CHM, Kool M, Kraaijvanger R, Grutters JC, Overgaauw M, Veltkamp M, Wijsenbeek MS; Collaborating investigators. Design of a randomized controlled trial to evaluate effectiveness of methotrexate versus prednisone as first-line treatment for pulmonary sarcoidosis: the PREDMETH study. BMC Pulm Med. 2020 Oct 19;20(1):271. doi: 10.1186/s12890-020-01290-9.

  PMID: 33076885 DERIVED

MeSH Terms

Conditions

Sarcoidosis, Pulmonary; Sarcoidosis

Interventions

Methotrexate; Prednisone

Condition Hierarchy (Ancestors)

Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Hypersensitivity, Delayed; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Marlies Wijsenbeek, MD PhD

  Erasmus Medical Center

  PRINCIPAL INVESTIGATOR

• Marcel Veltkamp, MD PhD

  St. Antonius Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Model Details: Prospective, randomized, open-label, multi-center (17 hospitals in the Netherlands), single country, non-inferiority trial. Randomization 1:1 to oral prednisone (start 40 mg daily, to be tapered to 10 mg daily) or oral methotrexate (15 mg weekly to be increased to 25 mg weekly) for 24 weeks. Thereafter continuation of trial for 18 months on regular treatment (investigator decision).

Study Record Dates

• First Submitted: February 24, 2020
• First Posted: March 19, 2020
• Study Start: June 1, 2020
• Primary Completion: August 13, 2024
• Study Completion (Estimated): July 1, 2026
• Last Updated: March 26, 2025

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

NL (17)