Kinetics of Elimination of Methotrexate and Its Major Metabolite 7-OH-methotrexate for Observant Patients
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- CHU de Reims
- Enrollment
- 62
- Locations
- 2
- Primary Endpoint
- Urinary concentration of methotrexate and its major metabolite 7-OH-methotrexate
Study Overview
Brief Summary
Methotrexate is a key treatment for inflammatory rheumatism. Therapeutic compliance with methotrexate is difficult to measure because of a lack of objective testing; however, therapeutic compliance is essential for the proper management of a patient.
The objective is to characterize the kinetics of elimination of methotrexate and its main metabolite7-OH-methotrexate for observant patients according to treatment (dosage, administration) and patient characteristics.
Once this kinetics is characterized, it will be considered as a comparison reference to identify non-observant patients that is to say having concentrations lower than the lower bound of the confidence interval of the observed concentrations.
Detailed Description
Type of study: prospective longitudinal descriptive observational study Population: Patients treated for rheumatoid arthritis in the Rheumatology Department of Reims University Hospital and treated with methotrexate monotherapy (weekly intake).
Assessment Criteria: Urinary concentration of methotrexate and its metabolite 7-OH-methotrexate at different days post-administration.
Investigation plan: Determination of urinary methotrexate and its 7-OH-methotrexate metabolite on 8 urine samples (just before taking, then 2 hours after treatment and then on D3, D4, D5, D6, D7, D8 before re-taking methotrexate) in the same patient treated with methotrexate weekly. It will take 10 patients per dosage level, followed by 3 to 8 days post-administration, to distinguish the urinary methotrexate concentrations of observant patients from those of non-observant patients with the power of 90%.
Statistical Analysis Plan: The main objective of this study is to characterize the elimination kinetics of methotrexate and its major metabolite 7-OH-methotrexate in patients observing the various methotrexate regimens. Once this kinetics is characterized, it will be considered as a comparison reference to identify non-observant patients that is to say having concentrations lower than the lower bound of the confidence interval of the observed concentrations.
On the one hand, simulations based on published population pharmacokinetic models of plasma methotrexate are used to estimate the periods of elimination of methotrexate. The simulations that the investigators carried out on the basis of these models highlight that these elimination periods are between 3 and at the latest 9.5 days. These periods correspond to the time required to eliminate 99% of methotrexate.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •All patients managed for rheumatoid arthritis (according to the ACR / EULAR 2010 criteria) in the Rheumatology Department of the University Hospital of Reims and treated with methotrexate monotherapy.
- •Patient affiliated to a social security scheme.
Exclusion Criteria
- •Patient protected by law.
Outcomes
Primary Outcomes
Urinary concentration of methotrexate and its major metabolite 7-OH-methotrexate
Time Frame: Day 8
LC-MS/MS quantification (in nM)
Secondary Outcomes
No secondary outcomes reported