This study has been transitioned to CTIS with ID 2024-514055-15-00 check the CTIS register for the current data. Primary: • Investigate the effectiveness and tolerability of methotrexate as first-line therapy in patients with pulmonary sarcoidosis…
ID
Source
Brief title
Condition
- Respiratory disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The change in hospital-measured Forced Vital Capacity (FVC) between baseline
and 24 weeks...
Secondary outcome
Other pulmonary function parameters, biomarkers, adverse events, quality of
life.
Background summary
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limited, outdated and largely based on expert opinion.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. We hypothesize that first-line treatment with methotrexate is as
effective as prednisone, with fewer side-effects and better QoL
Study objective
This study has been transitioned to CTIS with ID 2024-514055-15-00 check the CTIS register for the current data.
Primary:
• Investigate the effectiveness and tolerability of methotrexate as first-line
therapy in patients with pulmonary sarcoidosis compared with prednisone.
Secondary:
• Examine (immunological) biomarkers of disease progression and chronicity.
• Assess whether response to therapy can be predicted in individual patients.
• Gain more insights into the underlying disease mechanism and potential new
targets
Study design
Phase 4, prospective, randomized, open-label, multi-center, 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). 138 randomized patients.
Intervention
Treatment with prednisone or methotrexate.
Study burden and risks
Risk: Adverse effects of study treatment.
Burden:
Physical examination: every visit (=6 times).
Blood tests: every visit 80 mL per occasion
Pulmonary function: every visit.
FVC measurement at home: weekly, 24 weeks.
Questionnaires: King*s Sarcoidosis Questionnaire, General Rating of Change,
EQ-5D-5L, Patient Experience and Satisfaction with Medication Questionnaire,
VAS of Dyspnea, Cough, Fatigue, Complaints, MRC Dyspnea Scale, Fatigue
Assessment Scale: every visit.
VAS at home: symptoms and side effects: weekly, 24 weeks.
's-Gravendijkwal 230
Rotterdam 3015 GE
NL
's-Gravendijkwal 230
Rotterdam 3015 GE
NL
Listed location countries
Age
Inclusion criteria
- Diagnosis of sarcoidosis according to the ATS/ERS/WASOG criteria (7), 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 (18, 19)
- 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
decline/>=10% DLCO decline in the past year. For pulmonary functions tests GLI
reference values are used.
Exclusion criteria
- 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
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2024-514055-15-00 |
| EudraCT | EUCTR2019-004148-31-NL |
| CCMO | NL71782.078.19 |