Effect of Tofacitinib on Coagulation and Platelet Function, and Its Role in Thromboembolic Events

GIS-2021-JAKihemo

Post-authorization, prospective and unicenter clinical trial, in which patients with UC will be included. The treatment with anti-TNFα (infliximab, adalimumab or golimumab) or JAK-inhibitors (tofacitinib) will be initiated by clinical practice and the choice will be made at the discretion of the investigator at the center where the patients will be recruited (Hospital Universitario de La Princesa). In the case of the group of patients treated with tofacitinib, the selection will be made following the action protocol implemented in our center, in which this drug is usually reserved for those cases refractory to anti-TNFα and/or vedolizumab. There will be no random assignment of treatment. The drugs will be used in the approved indications and conditions of use.

2022-04-01

2024-10-01

2024-10-01

Recruiting

Early phase I

30

Inclusion Criteria: EX VIVO STUDY IN PATIENTS WITH UC PATIENTS WITH UC: * Over 18 years old. * Diagnosis of UC according to the criteria of the European Crohn's and Colitis Organisation (ECCO). * Previous treatments are allowed, provided they have remained stable for the past 3 months. * In the case of patients with active UC, they should have endoscopic activity within 1 month of starting the treatment (Mayo endoscopic sub-index of ≥ 2). * Women of childbearing age using contraceptive methods with an error rate \<1% per year. Examples of contraceptive methods whose error rate is \<1% per year are: 1. Intrauterine device (IUD). 2. Bilateral tubal occlusion. 3. Couple with vasectomy. 4. Sexual abstinence. INDIVIDUALS WITHOUT UC: * Over 18 years old. * Subjects not diagnosed with UC, or other inflammatory allergic, malignant or autoimmune diseases. * Women of childbearing age using contraceptive methods with an error rate \<1% per year. Examples of contraceptive methods whose error rate is \<1% per year are: 1. Intrauterine device (IUD). 2. Bilateral tubal occlusion. 3. Couple with vasectomy. 4. Sexual abstinence. IN VIVO STUDY IN PATIENTS WITH UC PATIENTS WITH UC: * Over 18 years old. * Diagnosis of UC according to the criteria of the European Crohn's and Colitis Organisation (ECCO). * Have indication of treatment with anti-TNFα (infliximab, adalimumab or golimumab) o tofacitinib. * Be the first received JAK-inhibitor or anti-TNFα with a given mechanism of action. * Have endoscopic activity of UC within 1 month of starting the treatment (Mayo endoscopic sub-index of ≥ 2). * Previous treatments (including corticosteroids and immunosuppressants) are allowed provided that they have been stable for the last 3 months before beginning treatment with JAK-inhibitor or anti-TNFα and that they are maintained at a stable dose for the duration of the study * Women of childbearing age using contraceptive methods with an error rate \<1% per year. Examples of contraceptive methods whose error rate is \<1% per year are: 1. Intrauterine device (IUD). 2. Bilateral tubal occlusion. 3. Couple with vasectomy. 4. Sexual abstinence. INDIVIDUALS WITHOUT UC: * Over 18 years old. * Subjects not diagnosed with UC, or other inflammatory, allergic, malignant or autoimmune diseases. * Women of childbearing age using contraceptive methods with an error rate \<1% per year. Examples of contraceptive methods whose error rate is \<1% per year are: 1. Intrauterine device (IUD). 2. Bilateral tubal occlusion. 3. Couple with vasectomy. 4. Sexual abstinence. Exclusion Criteria: EX VIVO STUDY IN PATIENTS WITH UC PATIENTS WITH UC: * Under 18 years old. * Immune-mediated disease, neoplasm or active infection. * Pregnancy or lactation. * Alcohol or drug abuse. * Ostomy. * Abdominal surgery in the last 6 months. * Colectomy. * Active infection with hepatitis B, C or HIV virus. * Medical history of thromboembolic events. * Treatment with anticoagulants, antiplatelets or other drugs that alter the coagulation. * Use of combined hormonal contraceptives or hormone replacement therapy. * Hereditary coagulation disorders. * Refusal to give consent for participation in the study. INDIVIDUALS WITHOUT UC: * Under 18 years of age. * Advanced chronic disease or any other pathology that prevents the monitoring of the protocol of this study. * Pregnancy or lactation. * Alcohol or drug abuse. * Ostomy. * Abdominal surgery in the last 6 months. * Colectomy. * Active infection with hepatitis B, C or HIV virus. * Medical history of thromboembolic events. * Treatment with anticoagulants, antiplatelets or other drugs that alter the coagulation. * Use of combined hormonal contraceptives or hormone replacement therapy. * Hereditary coagulation disorders. * Refusal to give consent for participation in the study. IN VIVO STUDY IN PATIENTS WITH UC PATIENTS WITH UC: * Under 18 years old. * Immune-mediated disease. * Neoplasm or active infection. * Pregnancy or lactation. * Alcohol or drug abuse. * Ostomy. * Colectomy. * Active infection with hepatitis B, C or HIV virus. * Indication of anti-TNFα or JAK-inhibitors treatment for a cause other than UC. * Have previously received a drug with the same mechanism of action (anti-TNFα or JAK-inhibitors) * Medical history of thromboembolic events. * Treatment with anticoagulants, antiplatelets or other drugs that alter the coagulation. * Use of combined hormonal contraceptives or hormone replacement therapy. * Hereditary coagulation disorders. * Refusal to give consent for participation in the study. INDIVIDUALS WITHOUT UC: * Under 18 years of age. * Advanced chronic disease or any other pathology that prevents the monitoring of the protocol of this study. * Pregnancy or lactation. * Alcohol or drug abuse. * Active infection with hepatitis B, C or HIV virus. * Finding of macroscopic alterations during the colonoscopy or finding of relevant inflammatory alterations in the biopsies obtained during the colonoscopy. * Treatment with immunomodulators, immunosuppressants, corticosteroids or other drugs that alter the immune system. * Medical history of thromboembolic events. * Treatment with anticoagulants, antiplatelets or other drugs that alter the coagulation. * Use of combined hormonal contraceptives or hormone replacement therapy. * Hereditary coagulation disorders. * Refusal to give consent for participation in the study. * Abdominal surgery in the last 6 months.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE4'], 'designInfo': {'allocation': 'NON_RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 30, 'type': 'ESTIMATED'}}

2023-11-18