Mesalazine Monotherapy Versus Thiopurine Continuation in Older Patients with Ulcerative Colitis in Sustained Remission: Multicenter Randomized Trial
- Trial ID
- 2025-524675-23-00
- Protocol
- IDEA
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the biological recurrence rate at 24 months of follow-up in elderly patients with ulcerative colitis in sustained remission following the discontinuation of thiopurines compared to those who continue treatment. This evaluation is clinically relevant to determine the feasibility of reducing immunosuppressive therapy in older populations with quiescent disease.
Secondary objectives include:
- Identification of factors associated with clinical and biological recurrence or colectomy after thiopurine withdrawal.
- Assessment of clinical and biological remission rates after discontinuation.
- Description of the time to clinical and biological recurrence.
- Comparison of safety profiles between both strategies, including rates of adverse effects, hospitalization due to disease flare-ups or complications, hospitalization due to adverse effects, colectomy, and disease-related or adverse effect-associated mortality.
- Long-term passive follow-up to determine the requirement for advanced therapies or additional immunosuppressants, colectomy, and associated clinical outcomes.
Participants
The sponsor did not provide information regarding the total number of participants. The study population consists of male and female patients diagnosed with ulcerative colitis. The cohort is characterized by advanced age, specifically within the defined age ranges. Eligible individuals must have a diagnosis established according to ECCO criteria and have maintained clinical remission for a minimum of 3 years. Participants are required to have undergone long-term treatment with thiopurines, such as azathioprine or mercaptopurine, for at least 5 consecutive years at stable doses. Required conditions for inclusion include endoscopic remission confirmed by colonoscopy and subclinical inflammatory remission as indicated by faecal calprotectin levels. The study objectives are:
- To evaluate the biological recurrence rate at 24 months of follow-up after the discontinuation of thiopurines in patients with quiescent disease in prolonged remission and advanced age compared to those who continue treatment.
Plans and Procedures
This multicenter, randomized controlled trial evaluates the biological recurrence rate in older patients with ulcerative colitis in sustained remission. The study compares the transition to mesalazine monotherapy against the continuation of thiopurines. The research follows a 24-month follow-up period to assess outcomes. The study process begins with a screening visit to verify inclusion criteria, such as age 60 years or older, established diagnosis, and stable treatment with azathioprine or mercaptopurine for at least five years. Participants must demonstrate clinical, endoscopic, and subclinical inflammatory remission at the time of inclusion. Following randomization, the study monitors patients to identify the primary endpoint, which is biological recurrence defined by specific faecal calprotectin levels or clinical recurrence requiring treatment intensification. Secondary endpoints include colectomy rate, mortality, and hospitalisation rate. The overall duration of participant involvement is determined by the 24-month observation period. Early termination may occur based on clinical necessity or protocol deviations.
Treatment
The experimental treatment consists of mesalazine administered at a total daily dose of 4 g via the oral route. The medication is provided in various pharmaceutical forms, including prolonged-release granules, gastro-resistant tablets, and prolonged-release tablets. Specific commercial products utilized for this intervention include Salofalk, Pentasa, Asacol, and Claversal.
Efficacy
The primary efficacy endpoint is biological recurrence, defined as faecal calprotectin levels exceeding 250 µg/g confirmed in two consecutive samples or clinical recurrence necessitating treatment intensification within a 24-month follow-up period. Secondary endpoints include time to relapse, clinical recurrence rate, colectomy rate, mortality, and hospitalisation rate related to disease activity or adverse events. Safety and adverse events will also be monitored. Treatment adherence will be assessed using the Morisky-Green scale.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Age 60 years or older.
- Established diagnosis of ulcerative colitis according to ECCO criteria.
- Treatment with azathioprine (AZA; 1–2.5 mg/kg/day) or mercaptopurine (MP; 0.75–1.5 mg/kg/day) for ≥5 consecutive years, at stable doses (minimum effective dose without adverse effects) during the last 12 months.
- In the case of concomitant treatment with oral mesalazine, stable doses for the last 12 months.
- Clinical remission maintained for ≥3 years, in the investigator's opinion, defined as: i. Absence of flare-ups requiring systemic corticosteroids (oral or IV) or biological agents. ii. The use of stable oral mesalazine and/or topical rectal treatments is permitted if the dose has remained stable over the last 12 months.
- Objective clinical remission at the inclusion visit: (1) Partial Mayo index ≤2 (with rectal bleeding subindex equal to 0).
- Endoscopic remission confirmed by colonoscopy performed within 12 months prior to study inclusion with endoscopic Mayo subindex=0 according to clinical practice.
- Subclinical inflammatory remission: Baseline faecal calprotectin ≤150 mg/kg, measured approximately 1 month (+/- 1 week) prior to randomisation.
- Written informed consent.
Exclusion Criteria
- Ulcerative proctitis (maximum extent observed <25 cm during the course of the disease).
- Total or segmental colectomy
- Ileoanal reservoir
- History of complex perianal disease
- Intolerance to oral 5-ASA
- Current or previous treatment with any selective immunomodulator or advanced therapy approved for the treatment of ulcerative colitis for any indication.
- Cessation of topical treatment (mesalazine or steroids) in the 3 months prior to inclusion
- CRF with creatinine ≥2mg/dl (glomerular filtration rate ≤ 30mL/min/1.73m2)
- Abnormal liver function tests (AST, ALT, alkaline phosphatase or GGT elevated >2 times the upper limit of normal) at the time of inclusion
- Neutrophil count <1500x10⁶ cells/mm³, lymphocytes <500x10⁶ cells/mm³, platelets <120,000x10⁶ cells/mm³, haemoglobin <12 g/dL (women) or 13 g/dL (men) at the time of inclusion.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Spain | Recruiting | 01 May 2026 | 304 |
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 |
|---|---|---|---|---|---|---|
Salofalk 1000 mg granulado de liberación prolongada | Test | GRANULADO DE LIBERACIÓN PROLONGADA | ORAL USE | 4 | 24 | PRD831725 |
Pentasa 4 g granulado de liberación prolongada | Test | GRANULADO DE LIBERACIÓN PROLONGADA | ORAL USE | 4 | 24 | PRD3516948 |
Asacol 1600 mg comprimidos gastrorresistentes | Test | COMPRIMIDOS GASTRORRESISTENTES | ORAL USE | 4 | 24 | PRD9295822 |
Claversal 500 mg comprimidos gastrorresistentes | Test | COMPRIMIDOS GASTRORRESISTENTES | ORAL USE | 4 | 24 | PRD439613 |
Asacol 800 mg comprimidos gastrorresistentes | Test | COMPRIMIDOS GASTRORESISTENTES | ORAL USE | 4 | 24 | PRD2688405 |
PENTASA 500 mg comprimidos de liberación prolongada | Test | COMPRIMIDOS DE LIBERACIÓN PROLONGADA | ORAL USE | 4 | 24 | PRD12526485 |
Pentasa 4 g granulado de liberación prolongada | Test | GRANULADO DE LIBERACIÓN PROLONGADA | ORAL USE | 4 | 24 | PRD12529103 |
Pentasa 1g granulado de liberación prolongada | Test | GRANULADO DE LIBERACIÓN PROLONGADA | ORAL USE | 4 | 24 | PRD474830 |
PENTASA 500 mg comprimidos de liberación prolongada | Test | COMPRIMIDOS DE LIBERACIÓN PROLONGADA | ORAL USE | 4 | 24 | PRD474857 |
Pentasa 2g granulado de liberación prolongada | Test | GRANULADO DE LIBERACIÓN PROLONGADA | ORAL USE | 4 | 24 | PRD474846 |