Sarcoidosis, PulmonaryPhase 4PREDMETHNCT04314193
Effectiveness of Methotrexate Versus Prednisone as First-line Therapy for Pulmonary Sarcoidosis
A Phase 4 study testing Methotrexate and Prednisone in people with Sarcoidosis, Pulmonary, run by Erasmus Medical Center at 17 sites in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sarcoidosis, Pulmonary
- What is being tested?
- Methotrexate and Prednisone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 138 participants
- Where
- 17 sitesNetherlands
- Study dates
- 1 Jun 2020to Jul 2026
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 pulmonary indication for treatment and parenchymal involvement on X-ray or CT-scan conducted within three months before inclusion (determined by the treating physician and conform current guidelines).
- 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.
Who cannot join
- 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:
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- 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
Trial locations and contacts
17 sites in 1 country.
17 sites in 1 country
Netherlands17 sites
Jeroen Bosch Ziekenhuis
's-Hertogenbosch, 5223 GZ
Vrije Universiteit Medisch Centrum
Amsterdam, 1007 MB
Onze Lieve Vrouwe Gasthuis
Amsterdam, 1061 AC
Academisch Medisch Centrum
Amsterdam, 1105 AZ
Rijnstate Ziekenhuis
Arnhem, 6815 AD
Amphia hospital
Breda
Catharina Ziekenhuis
Eindhoven
Medisch Spectrum Twente
Enschede, 7512 KZ
Martini Ziekenhuis
Groningen, 9728 NT
Zuyderland Medisch Centrum
Heerlen, 6419 PC
Medical Center Leeuwarden
Leeuwarden
Leids Universitair Medisch Centrum
Leiden, 2333 ZA
Haaglanden Medisch Centrum
Leidschendam, 2262 BA
Sint Antonius Ziekenhuis
Nieuwegein, 3425 CM
Erasmus MC
Rotterdam, 3000 CA
VieCuri Medical Center
Venlo
Isala Klinieken
Zwolle, 8025 AB
About this study
Official title: The PREDMETH Trial: Effectiveness of Methotrexate Versus Prednisone as First-line Therapy for Pulmonary Sarcoidosis - A Randomized Controlled Trial
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.
Read the detailed description
Sarcoidosis is a multisystem, granulomatous disorder, most commonly affecting the lungs. Symptom burden is high, and quality of life (QoL) and social participation are negatively affected. In patients with pulmonary sarcoidosis, treatment is recommended in case of significant symptoms and/or impaired or deteriorating lung function. Evidence-based treatment recommendations are limited, outdated and largely based on expert opinion.
Prednisone is currently the first-choice therapy in pulmonary sarcoidosis and leads to short-term improvement of lung function. Unfortunately, prednisone has major side-effects and is associated with impaired QoL. Methotrexate is presently considered second-line therapy, and appears to have fewer side-effects. The investigators hypothesize that first-line treatment with methotrexate is as effective as prednisone, with fewer side-effects and better QoL.
- Conditions
- Sarcoidosis, Pulmonary
- Being tested
- Methotrexate, Prednisone
- Keywords
- sarcoidosis, pulmonary, prednisone, methotrexate
- Medical subject headings
- Sarcoidosis, Pulmonary, Sarcoidosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MethotrexateDrug
Oral methotrexate (15 mg weekly to be increased to 25 mg weekly) for 24 weeks.
PrednisoneDrug
Oral prednisone (start 40 mg daily, to be tapered to 10 mg daily) for 24 weeks.
| Study group | Role | What they receive |
|---|---|---|
| methotrexate | Experimental | Not described Receives: Drug: Methotrexate |
| prednisone | Active comparator | Not described Receives: Drug: Prednisone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Forced Vital Capacity (FVC)
Change in hospital-measured FVC between baseline and 24 weeks
Measured: 24 weeks after inclusion
Secondary outcomes (79)
Forced Vital Capacity (FVC)
Change in hospital-measured FVC between baseline and 4 weeks.
Measured: 4 weeks
Forced Vital Capacity (FVC)
Change in hospital-measured FVC between baseline and 16 weeks.
Measured: 16 weeks
Time to major pulmonary improvement measured by FVC
Time to major pulmonary improvement measured by home-measured FVC, whereby major pulmonary improvement is defined as 80% of the maximum percent predicted FVC reached anywhere during the first 24 weeks of treatment. This will be determined on the home spirometry data.
Measured: 24 weeks
Change in FVC
The percentage of patients with a 5 and 10% improvement or decline in FVC at 4 weeks.
Measured: 4 weeks
Change in FVC
The percentage of patients with a 5 and 10% improvement or decline in FVC at 16 weeks.
Measured: 16 weeks
Change in FVC
The percentage of patients with a absolute 5 and 10% improvement or decline in percent predicted FVC at 24 weeks.
Measured: 24 weeks
Change in DLCO
The percentage of patients with a 10% or > 10% improvement or decline in DLCO at 4 weeks.
Measured: 4 weeks
Change in DLCO
The percentage of patients with a 10% or > 10% improvement or decline in DLCO at 16 weeks.
Measured: 16 weeks
Change in DLCO
The percentage of patients with a 10% or > 10% improvement or decline in DLCO at 24 weeks.
Measured: 24 weeks
Changes in Angiotensin-Converting Enzyme (ACE)
Differences in serum levels of sACE (U/ml) in serum of sarcoidosis patients before, during and after treatment
Measured: 2 years
Between group changes in sACE levels during treatment
Differences in serum levels of sACE (U/ml) in serum of sarcoidosis patients on prednisolone versus methotrexate
Measured: 2 years
Changes in soluble interleukin-2 receptor (sIL-2R)
Differences in serum levels of sIL-2R (U/ml) in serum of sarcoidosis patients before, during and after treatment
Measured: 2 years
Between group changes in sIL-2R levels during treatment
Differences in serum levels of sIL-2R (U/ml) in serum of sarcoidosis patients on prednisolone versus methotrexate
Measured: 2 years
Changes in extracellular vesicles during treatment
Differences in absolute numbers of extracellular vesicles in serum of sarcoidosis patients before, during and after treatment
Measured: 2 years
Between group changes in extracellular vesicles absolute numbers
Differences in absolute numbers of extracellular vesicles in serum of sarcoidosis patients on prednisolone versus methotrexate
Measured: 2 years
Changes in protein expression levels in extracellular vesicles during treatment
Differences in protein expression in extracellular vesicles in serum of sarcoidosis patients before, during and after treatment
Measured: 2 years
Between group changes in protein expression levels in extracellular vesicles
Differences in protein expression in extracellular vesicles in serum of sarcoidosis patients on prednisolone versus methotrexate
Measured: 2 years
Changes in T lymphocyte phenotypes during Treatment
Flow cytometry analysis will be used to determine how the frequencies and distribution of different cell subtypes change during treatment. Different phenotypes can be identified through expression of a number of cell surface markers, expression is measured in MFI (mean fluorescence intensity).
Differences in phenotype of T-cells (MFI) in peripheral blood of sarcoidosis patients before, during and after treatment.
Measured: 2 years
Between group changes in T lymphocyte phenotypes
Flow cytometry analysis will be used to determine how the frequencies and distribution of different cell subtypes change during treatment. Different phenotypes can be identified through expression of a number of cell surface markers, expression is measured in MFI (mean fluorescence intensity).
Differences in phenotype of T-cells (MFI) in peripheral blood of sarcoidosis patients on prednisolone versus methotrexate
Measured: 2 years
Changes in T lymphocyte absolute cell numbers
Differences in the absolute numbers of T-cells (cells/ml) in peripheral blood of sarcoidosis patients before, during and after treatment
Measured: 2 years
Between group changes in T lymphocyte absolute cell numbers
Differences in the absolute numbers of T-cells (cells/ml) in peripheral blood of sarcoidosis patients on prednisolone versus methotrexate
Measured: 2 years
Changes in the distribution of T lymphocytes during treatment
Differences in the frequencies of T-cells (%) in peripheral blood of sarcoidosis patients before, during and after treatment
Measured: 2 years
Between group changes in the distribution of T lymphocytes
Differences in the frequencies of T-cells (%) in peripheral blood of sarcoidosis patients on prednisolone versus methotrexate
Measured: 2 years
Changes in dendritic cell phenotypes during Treatment
Flow cytometry analysis will be used to determine how the frequencies and distribution of different cell subtypes change during treatment. Different phenotypes can be identified through expression of a number of cell surface markers, expression is measured in MFI (mean fluorescence intensity).
Differences in phenotype of dendritic cells (MFI) in peripheral blood of sarcoidosis patients before, during and after treatment
Measured: 2 years
Between group changes in dendritic cell phenotypes
Flow cytometry analysis will be used to determine how the frequencies and distribution of different cell subtypes change during treatment. Different phenotypes can be identified through expression of a number of cell surface markers, expression is measured in MFI (mean fluorescence intensity).
Differences in phenotype of dendritic cells (MFI) in peripheral blood of sarcoidosis patients on prednisolone versus methotrexate
Measured: 2 years
Changes in dendritic cell absolute cell numbers
Differences in the absolute numbers of dendritic cells (cells/ml) in peripheral blood of sarcoidosis patients before, during and after treatment
Measured: 2 years
Between group changes in dendritic cell absolute cell numbers
Differences in the absolute numbers of dendritic cells (cells/ml) in peripheral blood of sarcoidosis patients on prednisolone versus methotrexate
Measured: 2 years
Changes in the distribution of dendritic cells during treatment
Differences in the frequencies of dendritic cells (%) in peripheral blood of sarcoidosis patients before, during and after treatment
Measured: 2 years
Between group changes in the distribution of dendritic cells
Differences in the frequencies of dendritic cells (%) in peripheral blood of sarcoidosis patients on prednisolone versus methotrexate
Measured: 2 years
Changes in monocyte subset phenotypes during Treatment
Flow cytometry analysis will be used to determine how the frequencies and distribution of different cell subtypes change during treatment. Different phenotypes can be identified through expression of a number of cell surface markers, expression is measured in MFI (mean fluorescence intensity).
Differences in expression of monocyte specific cell surface markers on monocytes (MFI) in peripheral blood of sarcoidosis patients before, during and after treatment
Measured: 2 years
Between group changes in monocyte subset phenotypes
Flow cytometry analysis will be used to determine how the frequencies and distribution of different cell subtypes change during treatment. Different phenotypes can be identified through expression of a number of cell surface markers, expression is measured in MFI (mean fluorescence intensity).
Differences expression of monocyte specific cell surface markers on monocytes (MFI) in peripheral blood of sarcoidosis patients on prednisolone versus methotrexate
Measured: 2 years
Changes in monocyte absolute cell numbers
Differences in the absolute numbers of monocytes (cells/ml) in peripheral blood of sarcoidosis patients before, during and after treatment
Measured: 2 years
Between group changes in monocyte absolute cell numbers
Differences in the absolute numbers of monocytes (cells/ml) in peripheral blood of sarcoidosis patients on prednisolone versus methotrexate
Measured: 2 years
Changes in the distribution of monocytes during treatment
Differences in the frequencies of monocytes in peripheral blood of sarcoidosis patients before, during and after treatment
Measured: 2 years
Between group changes in the distribution of monocytes
Differences in the frequencies of monocytes in peripheral blood of sarcoidosis patients on prednisolone versus methotrexate
Measured: 2 years
Correlation between biomarkers and clinical parameters
The differences in percentage of biomarkers is compared with the differences in change of FVC and DLCOc.
Biomarkers are measured in peripheral blood and include:
- monocytes, measured by flow cytometry (MFI)
- Th-cells, measured by flow cytometry (MFI)
- dendritic cells, measured by flow cytometry (MFI)
- Proteins, measured by ELISA (ng/ml)
- Serum biomarkers (U/l)
Measured: 2 years
The King's Sarcoidosis Questionnaire (KSQ)
The King's Sarcoidosis Questionnaire (KSQ) assesses health status in patients with sarcoidosis. It comprises 29 items in 5 subdomains: general health status, lung, medication, skin and eyes. All scores range from 0 to 100, higher scores signifying beter health status. It takes about 3-5 minutes to complete.
Measured: baseline
The King's Sarcoidosis Questionnaire (KSQ)
The King's Sarcoidosis Questionnaire (KSQ) assesses health status in patients with sarcoidosis. It comprises 29 items in 5 subdomains: general health status, lung, medication, skin and eyes. All scores range from 0 to 100, higher scores signifying beter health status. It takes about 3-5 minutes to complete.
Measured: baseline and 4 weeks after inclusion
The King's Sarcoidosis Questionnaire (KSQ)
The King's Sarcoidosis Questionnaire (KSQ) assesses health status in patients with sarcoidosis. It comprises 29 items in 5 subdomains: general health status, lung, medication, skin and eyes. All scores range from 0 to 100, higher scores signifying beter health status. It takes about 3-5 minutes to complete.
Measured: baseline and 16 weeks after inclusion
The King's Sarcoidosis Questionnaire (KSQ)
The King's Sarcoidosis Questionnaire (KSQ) assesses health status in patients with sarcoidosis. It comprises 29 items in 5 subdomains: general health status, lung, medication, skin and eyes. All scores range from 0 to 100, higher scores signifying beter health status. It takes about 3-5 minutes to complete.
Measured: baseline and 24 weeks after inclusion
The King's Sarcoidosis Questionnaire (KSQ)
The King's Sarcoidosis Questionnaire (KSQ) assesses health status in patients with sarcoidosis. It comprises 29 items in 5 subdomains: general health status, lung, medication, skin and eyes. All scores range from 0 to 100, higher scores signifying beter health status. It takes about 3-5 minutes to complete.
Measured: baseline and 1 year after inclusion
The King's Sarcoidosis Questionnaire (KSQ)
The King's Sarcoidosis Questionnaire (KSQ) assesses health status in patients with sarcoidosis. It comprises 29 items in 5 subdomains: general health status, lung, medication, skin and eyes. All scores range from 0 to 100, higher scores signifying beter health status. It takes about 3-5 minutes to complete.
Measured: baseline and 2 years after inclusion
The Chronic Respiratory Questionnaire (CRQ)
The Chronic Respiratory Questionnaire (CRQ) is a 20-item self-reported validated questionnaire for HRQOL in patients with chronic respiratory disease. Scores range from 0 - 100 and higher scores signifying beter health quality.The minimal clinically important difference (MCID) is 0,5 points per item. It takes about 3-5 minutes to complete.
Measured: baseline
The Chronic Respiratory Questionnaire (CRQ)
The Chronic Respiratory Questionnaire (CRQ) is a 20-item self-reported validated questionnaire for HRQOL in patients with chronic respiratory disease. Scores range from 0 - 100 and higher scores signifying beter health quality.The minimal clinically important difference (MCID) is 0,5 points per item. It takes about 3-5 minutes to complete.
Measured: baseline and 4 weeks after inclusion
The Chronic Respiratory Questionnaire (CRQ)
The Chronic Respiratory Questionnaire (CRQ) is a 20-item self-reported validated questionnaire for HRQOL in patients with chronic respiratory disease. Scores range from 0 - 100 and higher scores signifying beter health quality.The minimal clinically important difference (MCID) is 0,5 points per item. It takes about 3-5 minutes to complete.
Measured: baseline and 16 weeks after inclusion
The Chronic Respiratory Questionnaire (CRQ)
The Chronic Respiratory Questionnaire (CRQ) is a 20-item self-reported validated questionnaire for HRQOL in patients with chronic respiratory disease. Scores range from 0 - 100 and higher scores signifying beter health quality.The minimal clinically important difference (MCID) is 0,5 points per item. It takes about 3-5 minutes to complete.
Measured: baseline and 24 weeks after inclusion
The Chronic Respiratory Questionnaire (CRQ)
The Chronic Respiratory Questionnaire (CRQ) is a 20-item self-reported validated questionnaire for HRQOL in patients with chronic respiratory disease. Scores range from 0 - 100 and higher scores signifying beter health quality.The minimal clinically important difference (MCID) is 0,5 points per item. It takes about 3-5 minutes to complete.
Measured: baseline and 1 year after inclusion
The Chronic Respiratory Questionnaire (CRQ)
The Chronic Respiratory Questionnaire (CRQ) is a 20-item self-reported validated questionnaire for HRQOL in patients with chronic respiratory disease. Scores range from 0 - 100 and higher scores signifying beter health quality.The minimal clinically important difference (MCID) is 0,5 points per item. It takes about 3-5 minutes to complete.
Measured: baseline and 2 years after inclusion
The global rating of change scale (GRC)
The global rating of change scale (GRC) is a measure in which patients are asked to rate if their QOL is improved or deteriorated over a certain period of time on a scale from -7 to +7. It consists of one questions and takes <1 minute to complete.
Measured: baseline
The global rating of change scale (GRC)
The global rating of change scale (GRC) is a measure in which patients are asked to rate if their QOL is improved or deteriorated over a certain period of time on a scale from -7 to +7. It consists of one questions and takes <1 minute to complete.
Measured: baseline and 4 weeks after inclusion
The global rating of change scale (GRC)
The global rating of change scale (GRC) is a measure in which patients are asked to rate if their QOL is improved or deteriorated over a certain period of time on a scale from -7 to +7. It consists of one questions and takes <1 minute to complete.
Measured: baseline and 16 weeks after inclusion
The global rating of change scale (GRC)
The global rating of change scale (GRC) is a measure in which patients are asked to rate if their QOL is improved or deteriorated over a certain period of time on a scale from -7 to +7. It consists of one questions and takes <1 minute to complete.
Measured: baseline and 24 weeks after inclusion
The global rating of change scale (GRC)
The global rating of change scale (GRC) is a measure in which patients are asked to rate if their QOL is improved or deteriorated over a certain period of time on a scale from -7 to +7. It consists of one questions and takes <1 minute to complete.
Measured: baseline and 1 year after inclusion
The global rating of change scale (GRC)
The global rating of change scale (GRC) is a measure in which patients are asked to rate if their QOL is improved or deteriorated over a certain period of time on a scale from -7 to +7. It consists of one questions and takes <1 minute to complete.
Measured: baseline and 2 years after inclusion
The EuroQol five dimensions 5-level questionnaire (EQ-5D-5L)
Patients will complete the EQ-5D-5L questionnaire, a standardized instrument to measure health outcomes in two components: health description and valuation. It comprises five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression on a 5-point scale. From these 5 answers an index value is derived between 0 and 1, with a higher value corresponding with a better QoL. In the valuation part the patients' general health status is evaluated using a VAS-score from 0 to 100, with a higher score representing a better QoL.
Measured: baseline
The EuroQol five dimensions 5-level questionnaire (EQ-5D-5L)
Patients will complete the EQ-5D-5L questionnaire, a standardized instrument to measure health outcomes in two components: health description and valuation. It comprises five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression on a 5-point scale. From these 5 answers an index value is derived between 0 and 1, with a higher value corresponding with a better QoL. In the valuation part the patients' general health status is evaluated using a VAS-score from 0 to 100, with a higher score representing a better QoL.
Measured: baseline and 4 weeks after inclusion
The EuroQol five dimensions 5-level questionnaire (EQ-5D-5L)
Patients will complete the EQ-5D-5L questionnaire, a standardized instrument to measure health outcomes in two components: health description and valuation. It comprises five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression on a 5-point scale. From these 5 answers an index value is derived between 0 and 1, with a higher value corresponding with a better QoL. In the valuation part the patients' general health status is evaluated using a VAS-score from 0 to 100, with a higher score representing a better QoL.
Measured: baseline and 16 weeks after inclusion
The EuroQol five dimensions 5-level questionnaire (EQ-5D-5L)
Patients will complete the EQ-5D-5L questionnaire, a standardized instrument to measure health outcomes in two components: health description and valuation. It comprises five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression on a 5-point scale. From these 5 answers an index value is derived between 0 and 1, with a higher value corresponding with a better QoL. In the valuation part the patients' general health status is evaluated using a VAS-score from 0 to 100, with a higher score representing a better QoL.
Measured: baseline and 24 weeks after inclusion
The EuroQol five dimensions 5-level questionnaire (EQ-5D-5L)
Patients will complete the EQ-5D-5L questionnaire, a standardized instrument to measure health outcomes in two components: health description and valuation. It comprises five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression on a 5-point scale. From these 5 answers an index value is derived between 0 and 1, with a higher value corresponding with a better QoL. In the valuation part the patients' general health status is evaluated using a VAS-score from 0 to 100, with a higher score representing a better QoL.
Measured: baseline and 1 year after inclusion
The EuroQol five dimensions 5-level questionnaire (EQ-5D-5L)
Patients will complete the EQ-5D-5L questionnaire, a standardized instrument to measure health outcomes in two components: health description and valuation. It comprises five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression on a 5-point scale. From these 5 answers an index value is derived between 0 and 1, with a higher value corresponding with a better QoL. In the valuation part the patients' general health status is evaluated using a VAS-score from 0 to 100, with a higher score representing a better QoL.
Measured: baseline and 2 years after inclusion
The Medical Research Council Dyspnea scale
The Medical Research Council Dyspnea scale consists of one question measuring dyspnea on a scale from 0-5.
Measured: Baseline
The Medical Research Council Dyspnea scale
The Medical Research Council Dyspnea scale consists of one question measuring dyspnea on a scale from 0-5.
Measured: Baseline and 4 weeks after inclusion
The Medical Research Council Dyspnea scale
The Medical Research Council Dyspnea scale consists of one question measuring dyspnea on a scale from 0-5.
Measured: Baseline and 16 weeks after inclusion
The Medical Research Council Dyspnea scale
The Medical Research Council Dyspnea scale consists of one question measuring dyspnea on a scale from 0-5.
Measured: Baseline and 24 weeks after inclusion
The Medical Research Council Dyspnea scale
The Medical Research Council Dyspnea scale consists of one question measuring dyspnea on a scale from 0-5.
Measured: Baseline and 1 year after inclusion
The Medical Research Council Dyspnea scale
The Medical Research Council Dyspnea scale consists of one question measuring dyspnea on a scale from 0-5.
Measured: Baseline and 2 years after inclusion
The fatigue assessment scale (FAS)
The fatigue assessment scale (FAS) is a 10-item self-administered questionnaire about fatigue in patients with sarcoidosis. The score ranges from 5-50 points, with a score of ≥ 22 points as cut-off for fatigue. The MCID is 4 points or a 10% lower score.
Measured: Baseline
The fatigue assessment scale (FAS)
The fatigue assessment scale (FAS) is a 10-item self-administered questionnaire about fatigue in patients with sarcoidosis. The score ranges from 5-50 points, with a score of ≥ 22 points as cut-off for fatigue. The MCID is 4 points or a 10% lower score.
Measured: Baseline and 4 weeks after inclusion
The fatigue assessment scale (FAS)
The fatigue assessment scale (FAS) is a 10-item self-administered questionnaire about fatigue in patients with sarcoidosis. The score ranges from 5-50 points, with a score of ≥ 22 points as cut-off for fatigue. The MCID is 4 points or a 10% lower score.
Measured: Baseline and 16 weeks after inclusion
The fatigue assessment scale (FAS)
The fatigue assessment scale (FAS) is a 10-item self-administered questionnaire about fatigue in patients with sarcoidosis. The score ranges from 5-50 points, with a score of ≥ 22 points as cut-off for fatigue. The MCID is 4 points or a 10% lower score.
Measured: Baseline and 24 weeks after inclusion
The fatigue assessment scale (FAS)
The fatigue assessment scale (FAS) is a 10-item self-administered questionnaire about fatigue in patients with sarcoidosis. The score ranges from 5-50 points, with a score of ≥ 22 points as cut-off for fatigue. The MCID is 4 points or a 10% lower score.
Measured: Baseline and 1 year after inclusion
The fatigue assessment scale (FAS)
The fatigue assessment scale (FAS) is a 10-item self-administered questionnaire about fatigue in patients with sarcoidosis. The score ranges from 5-50 points, with a score of ≥ 22 points as cut-off for fatigue. The MCID is 4 points or a 10% lower score.
Measured: Baseline and 2 years after inclusion
Number of patients who discontinue/switch medication
Every week patients register whether they missed pills (and the amount of pills wasted). Discontinuation or switch of medication is registered both by patients and researchers.
Measured: During 24 weeks
Patient Experience and Satisfaction with Medication questionnaire
Correlation between patient expectations with medication and consecutive experiences measured with the PESaM questionnaire which assess patient expectations at baseline in an 11-item questionnaire and patient experiences and side-effects with medication after 12 weeks in a 26-item questionnaire on a 0-4 Likert scale. For each question it is different whether a higher score represents better or worse outcomes.
Measured: baseline
Patient Experience and Satisfaction with Medication questionnaire
Correlation between patient expectations with medication and consecutive experiences measured with the PESaM questionnaire which assess patient expectations at baseline in an 11-item questionnaire and patient experiences and side-effects with medication after 12 weeks in a 26-item questionnaire on a 0-4 Likert scale. For each question it is different whether a higher score represents better or worse outcomes.
Measured: 4 weeks
Patient Experience and Satisfaction with Medication questionnaire
Correlation between patient expectations with medication and consecutive experiences measured with the PESaM questionnaire which assess patient expectations at baseline in an 11-item questionnaire and patient experiences and side-effects with medication after 12 weeks in a 26-item questionnaire on a 0-4 Likert scale. For each question it is different whether a higher score represents better or worse outcomes.
Measured: 16 weeks
Patient Experience and Satisfaction with Medication questionnaire
Correlation between patient expectations with medication and consecutive experiences measured with the PESaM questionnaire which assess patient expectations at baseline in an 11-item questionnaire and patient experiences and side-effects with medication after 12 weeks in a 26-item questionnaire on a 0-4 Likert scale. For each question it is different whether a higher score represents better or worse outcomes.
Measured: 24 weeks
Patient Experience and Satisfaction with Medication questionnaire
Correlation between patient expectations with medication and consecutive experiences measured with the PESaM questionnaire which assess patient expectations at baseline in an 11-item questionnaire and patient experiences and side-effects with medication after 12 weeks in a 26-item questionnaire on a 0-4 Likert scale. For each question it is different whether a higher score represents better or worse outcomes.
Measured: 1 year
Patient Experience and Satisfaction with Medication questionnaire
Correlation between patient expectations with medication and consecutive experiences measured with the PESaM questionnaire which assess patient expectations at baseline in an 11-item questionnaire and patient experiences and side-effects with medication after 12 weeks in a 26-item questionnaire on a 0-4 Likert scale. For each question it is different whether a higher score represents better or worse outcomes.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2020
- Study start1 Jun 2020
- Primary completion13 Aug 2024
- Study completionJul 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Sarcoidosis, PulmonaryStudies of the same condition, open and under way.
- More trials run by Erasmus Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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).
- Masking
- None (open label)
- Enrolment
- 138 participants (actual)
Sponsor and investigators
- Lead sponsor
- Erasmus Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- St. Antonius Hospital, Longfonds
- Responsible party
- Principal investigator, Marlies Wijsenbeek, Erasmus Medical Center
- Investigators
- Marlies Wijsenbeek, MD PhD, Principal investigator, Erasmus Medical CenterMarcel Veltkamp, MD PhD, Principal investigator, St. Antonius Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04314193
- Sponsor's protocol ID
- NL71782.078.19
- Acronym
- PREDMETH
- Status last verified
- Mar 2024
- First submitted
- 24 Feb 2020
- Last updated
- 26 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 40387020Kahlmann 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.
PubMed 33076885
Study at a glance
From the registry record, last updated by the sponsor on 26 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The PREDMETH Trial: Effectiveness of Methotrexate Versus Prednisone as First-line Therapy for Pulmonary Sarcoidosis - A Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT04314193
- Acronym / sponsor ID
- PREDMETH / NL71782.078.19
- Conditions
- Sarcoidosis, Pulmonary
- Keywords
- sarcoidosis, pulmonary, prednisone, methotrexate
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 138 participants (actual)
- Lead sponsor
- Erasmus Medical CenterUniversity, hospital or other
- Collaborators
- St. Antonius Hospital, Longfonds
- Study start
- 1 Jun 2020 (actual)
- Primary completion
- 13 Aug 2024 (actual)
- Study completion
- Jul 2026 (estimated)
- First posted
- 19 Mar 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Sarcoidosis is a multisystem, granulomatous disorder, most commonly affecting the lungs. Symptom burden is high, and quality of life (QoL) and social participation are negatively affected. In patients with pulmonary sarcoidosis, treatment is recommended in case of significant symptoms and/or impaired or deteriorating lung function. Evidence-based treatment recommendations are limited, outdated and largely based on expert opinion.
Prednisone is currently the first-choice therapy in pulmonary sarcoidosis and leads to short-term improvement of lung function. Unfortunately, prednisone has major side-effects and is associated with impaired QoL. Methotrexate is presently considered second-line therapy, and appears to have fewer side-effects. The investigators hypothesize that first-line treatment with methotrexate is as effective as prednisone, with fewer side-effects and better QoL.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 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).
| Arm | Type | Receives |
|---|---|---|
| methotrexate | Experimental | Drug: Methotrexate |
| prednisone | Active comparator | Drug: Prednisone |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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 pulmonary indication for treatment and parenchymal involvement on X-ray or CT-scan conducted within three months before inclusion (determined by the treating physician and conform current guidelines).
- 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.
Key exclusion criteria (11 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MethotrexateOral methotrexate (15 mg weekly to be increased to 25 mg weekly) for 24 weeks. | Drug | methotrexate |
| PrednisoneOral prednisone (start 40 mg daily, to be tapered to 10 mg daily) for 24 weeks. | Drug | prednisone |
Primary outcome
Forced Vital Capacity (FVC)
Time frame: 24 weeks after inclusion
Change in hospital-measured FVC between baseline and 24 weeks
79 secondary outcomes
Forced Vital Capacity (FVC)
Time frame: 4 weeks
Forced Vital Capacity (FVC)
Time frame: 16 weeks
Time to major pulmonary improvement measured by FVC
Time frame: 24 weeks
Change in FVC
Time frame: 4 weeks
Change in FVC
Time frame: 16 weeks
Change in FVC
Time frame: 24 weeks
Change in DLCO
Time frame: 4 weeks
Change in DLCO
Time frame: 16 weeks
Change in DLCO
Time frame: 24 weeks
Changes in Angiotensin-Converting Enzyme (ACE)
Time frame: 2 years
Between group changes in sACE levels during treatment
Time frame: 2 years
Changes in soluble interleukin-2 receptor (sIL-2R)
Time frame: 2 years
Between group changes in sIL-2R levels during treatment
Time frame: 2 years
Changes in extracellular vesicles during treatment
Time frame: 2 years
Between group changes in extracellular vesicles absolute numbers
Time frame: 2 years
Changes in protein expression levels in extracellular vesicles during treatment
Time frame: 2 years
Between group changes in protein expression levels in extracellular vesicles
Time frame: 2 years
Changes in T lymphocyte phenotypes during Treatment
Time frame: 2 years
Between group changes in T lymphocyte phenotypes
Time frame: 2 years
Changes in T lymphocyte absolute cell numbers
Time frame: 2 years
Between group changes in T lymphocyte absolute cell numbers
Time frame: 2 years
Changes in the distribution of T lymphocytes during treatment
Time frame: 2 years
Between group changes in the distribution of T lymphocytes
Time frame: 2 years
Changes in dendritic cell phenotypes during Treatment
Time frame: 2 years
Between group changes in dendritic cell phenotypes
Time frame: 2 years
Changes in dendritic cell absolute cell numbers
Time frame: 2 years
Between group changes in dendritic cell absolute cell numbers
Time frame: 2 years
Changes in the distribution of dendritic cells during treatment
Time frame: 2 years
Between group changes in the distribution of dendritic cells
Time frame: 2 years
Changes in monocyte subset phenotypes during Treatment
Time frame: 2 years
Between group changes in monocyte subset phenotypes
Time frame: 2 years
Changes in monocyte absolute cell numbers
Time frame: 2 years
Between group changes in monocyte absolute cell numbers
Time frame: 2 years
Changes in the distribution of monocytes during treatment
Time frame: 2 years
Between group changes in the distribution of monocytes
Time frame: 2 years
Correlation between biomarkers and clinical parameters
Time frame: 2 years
The King's Sarcoidosis Questionnaire (KSQ)
Time frame: baseline
The King's Sarcoidosis Questionnaire (KSQ)
Time frame: baseline and 4 weeks after inclusion
The King's Sarcoidosis Questionnaire (KSQ)
Time frame: baseline and 16 weeks after inclusion
The King's Sarcoidosis Questionnaire (KSQ)
Time frame: baseline and 24 weeks after inclusion
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Mar 2025.
- Derived from this study: PubMed 40387020Kahlmann 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.
- Derived from this study: PubMed 33076885Kahlmann 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marlies Wijsenbeek, MD PhD principal investigator
Erasmus Medical Center
Marcel Veltkamp, MD PhD principal investigator
St. Antonius Hospital
17 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Methotrexate and Prednisone in people with Sarcoidosis, Pulmonary, run by Erasmus Medical Center at 17 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 26 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Forced Vital Capacity (FVC) (time frame: 24 weeks after inclusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04314193, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Mar 2025.