A Randomized Controlled Trial Comparing Methotrexate and Prednisone as First-Line Therapy in Patients with Pulmonary Sarcoidosis
- Trial ID
- 2024-514055-15-00
- Protocol
- NL71782.078.19
Trial statistics
Diseases & Conditions
Objectives
The primary objective of the PREDMETH trial is to investigate the **effectiveness** and tolerability of **methotrexate** as a first-line therapy in patients with pulmonary sarcoidosis compared with **prednisone**. This is clinically relevant as it aims to determine whether methotrexate, an antimetabolite, can serve as an effective alternative to prednisone, a corticosteroid, potentially offering a different side effect profile and improving patient outcomes.
Secondary objectives include:
- Examining immunological biomarkers of disease progression and chronicity, which could provide insights into the disease's pathophysiology and help in monitoring disease activity.
- Assessing whether the response to therapy can be predicted in individual patients, which could lead to more personalized treatment approaches.
- Gaining more insights into the underlying disease mechanism and identifying potential new therapeutic targets, which could inform future treatment strategies and drug development.
Participants
The clinical trial focuses on evaluating the effectiveness and tolerability of methotrexate as a first-line therapy in patients with **pulmonary sarcoidosis** compared to prednisone. The study population includes both male and female participants aged 18 years and older. Participants are required to have a diagnosis of sarcoidosis according to the ATS/ERS/WASOG criteria, with a pulmonary indication for treatment and parenchymal involvement confirmed by X-ray or CT-scan. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants' general health status is assessed through pulmonary function tests, with specific criteria for forced vital capacity and diffusion capacity of the lung for carbon monoxide. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.
Plans and Procedures
The clinical trial is designed to evaluate the **effectiveness** and tolerability of **methotrexate** compared to **prednisone** as first-line therapy for patients with **pulmonary sarcoidosis**. This is a randomized, controlled trial with a double-blind design to ensure unbiased results. The trial is expected to span over a period of approximately five years, with an estimated recruitment start date of January 1, 2020, and an anticipated end date of March 1, 2025.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on specific criteria, such as a diagnosis of sarcoidosis according to ATS/ERS/WASOG criteria, age of 18 years or older, and specific pulmonary function test results. Following the screening, participants will be randomly assigned to receive either methotrexate or prednisone, both administered orally. The maximum daily dose for methotrexate is 24 mg, while for prednisone, it is 180 mg, with a treatment period of up to 24 weeks.
Throughout the trial, participants will attend regular follow-up visits to monitor their health status and treatment response. The primary endpoint is the change in hospital-measured Forced Vital Capacity (FVC), while secondary endpoints include the assessment of biomarkers. The end-of-study visit will conclude the participant's involvement, during which final assessments will be conducted to evaluate the overall effectiveness and safety of the treatment.
Participant involvement is expected to last for the duration of the treatment period, with conditions for early termination including adverse reactions, withdrawal of consent, or any other medical reasons deemed necessary by the investigators. The trial aims to provide valuable insights into the comparative effectiveness of methotrexate and prednisone, potentially influencing future treatment guidelines for pulmonary sarcoidosis.
Treatment
The clinical trial involves the administration of **methotrexate** as an experimental medication. Methotrexate is provided in the form of a tablet and is classified as an antimetabolite, specifically a folic acid antagonist. The active substance, methotrexate, is of chemical origin. The maximum daily dose is 24 mg, with a total maximum dose of 24 mg per day. The treatment period is set for a maximum of 24 weeks. Methotrexate is administered orally, and participant compliance is monitored throughout the trial to ensure adherence to the dosing schedule.
In addition to methotrexate, **prednisone** is used as a comparator treatment in the study. Prednisone is also provided in tablet form and is classified as a corticosteroid. The active substance, prednisone, is of chemical origin. The maximum daily dose for prednisone is 180 mg, with a total maximum dose of 180 mg per day. Similar to methotrexate, the treatment period for prednisone is also set for a maximum of 24 weeks. Prednisone is administered orally, and participant compliance is monitored to ensure proper adherence to the dosing regimen.
Both methotrexate and prednisone are utilized in this trial to evaluate their effectiveness and tolerability as first-line therapies for pulmonary sarcoidosis. The trial is designed to compare the outcomes of these two treatments, with a focus on determining the most effective and tolerable option for patients. Compliance monitoring is a critical component of the study to ensure accurate assessment of the treatment effects.
Efficacy
The efficacy of the clinical trial titled "The PREDMETH trial: Effectiveness of methotrexate versus prednisone as first-line therapy for pulmonary sarcoidosis" will be assessed using specific endpoints. The primary endpoint for evaluating efficacy is the change in hospital-measured **Forced Vital Capacity** (FVC). This parameter will be used to determine the effectiveness of the treatment in improving lung function in patients with pulmonary sarcoidosis.
Secondary endpoints include the measurement of biomarkers, which will provide additional insights into the biological effects of the treatments. The collection and analysis of these efficacy parameters will be conducted at specified intervals throughout the trial duration, although specific timepoints are not detailed in the provided data. The trial aims to compare the effectiveness and tolerability of methotrexate and prednisone, both administered in tablet form, as first-line therapies for this condition.
Inclusion and Exclusion Criteria
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.
- 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
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 The Netherlands | Recruiting | 01 Jan 2020 | — |
| Netherlands | — | — | 132 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
METHOTREXATE | Test | — | ORAL USE | 24 | 24 | SUB08856MIG |
METHOTREXATE | Test | — | ORAL USE | 24 | 24 | SUB08856MIG |
PREDNISONE | Test | — | ORAL USE | 180 | 24 | SUB10020MIG |
METHOTREXATE | Test | — | ORAL USE | 24 | 24 | SUB08856MIG |