Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05313620
Recruitment Status : Recruiting
First Posted : April 6, 2022
Last Update Posted : August 3, 2022
Sponsor:
Information provided by (Responsible Party):
Fundación de Investigación Biomédica - Hospital Universitario de La Princesa

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Ulcerative Colitis Thromboembolism Drug: Tofacitinib Drug: Infliximab Adalimumab y Golimumab Phase 4

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Effect of Tofacitinib on Coagulation and Platelet Function, and Its Role in Thromboembolic Events
Actual Study Start Date : April 1, 2022
Estimated Primary Completion Date : October 2023
Estimated Study Completion Date : October 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Ulcerative colitis patients treated with tofacitinib
Tofacitinib 5 mg/day oral per clinical practice
Drug: Tofacitinib
Tofacitinib 5 MG/day per clinical practice

Active Comparator: Ulcerative colitis patients treated with an anti-TNFα drug
Infliximab (Infusion 5mg/kg milligram(s)/Kilogram-Intravenous use) per clinical practice, or adalimumab (Subcutaneus 40 mg milligram(s)-subcutaneus) per clinical practice, or golimumab (subcutaneus 50 mg milligram(s)-subcutaneus) per clinical practice
Drug: Infliximab Adalimumab y Golimumab
Infliximab (Infusion 5mg/kg milligram(s)/Kilogram-Intravenous use) per clinical practice or adalimumab (Subcutaneus 40 mg milligram(s)-subcutaneus) per clinical practice or or golimumab (subcutaneus 50 mg milligram(s)-subcutaneus) per clinical practice.

No Intervention: healthy controls



Primary Outcome Measures :
  1. platelet activation [ Time Frame: 1 year ]
    Platelet activation status will be assessed ex vivo in platelet-rich plasma (PRP) samples from UC patients (active and quiescent) and healthy controls incubated in the absence or presence of drug (tofacitinib or anti-TNFα). Regarding the in vivo study, platelet activation will be analyzed in samples from patients with active UC before and after initiating treatment with tofacitinib or anti-TNFα. It will be mesured by rate of platelet agregation


Secondary Outcome Measures :
  1. Endoscopic activity [ Time Frame: 1 year ]
    It will be evaluated by the Mayo endoscopic sub-score; endoscopic activity will be considered as ≥ 2.

  2. Endoscopic response [ Time Frame: 1 year ]
    It will be defined as a decrease of ≥ 1 point in the Mayo endoscopic sub-score 3 months after starting treatment.

  3. Endoscopic remission [ Time Frame: 1 year ]
    It will be defined as an endoscopic subscore ≤1, 3 months after starting treatment.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05313620


Contacts
Layout table for location contacts
Contact: Sandra Hermida 913093911 sandra.hermida.hlp@gmail.com

Locations
Layout table for location information
Spain
Hospital Universitario de La Princesa Recruiting
Madrid, Spain, 28006
Contact: Javier P. Gisbert         
Sponsors and Collaborators
Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
Publications:
Burisch J, Pedersen N, Čuković-Čavka S, Brinar M, Kaimakliotis I, Duricova D, Shonová O, Vind I, Avnstrøm S, Thorsgaard N, Andersen V, Krabbe S, Dahlerup JF, Salupere R, Nielsen KR, Olsen J, Manninen P, Collin P, Tsianos EV, Katsanos KH, Ladefoged K, Lakatos L, Björnsson E, Ragnarsson G, Bailey Y, Odes S, Schwartz D, Martinato M, Lupinacci G, Milla M, De Padova A, D'Incà R, Beltrami M, Kupcinskas L, Kiudelis G, Turcan S, Tighineanu O, Mihu I, Magro F, Barros LF, Goldis A, Lazar D, Belousova E, Nikulina I, Hernandez V, Martinez-Ares D, Almer S, Zhulina Y, Halfvarson J, Arebi N, Sebastian S, Lakatos PL, Langholz E, Munkholm P; EpiCom-group. East-West gradient in the incidence of inflammatory bowel disease in Europe: the ECCO-EpiCom inception cohort. Gut. 2014 Apr;63(4):588-97. doi: 10.1136/gutjnl-2013-304636. Epub 2013 Apr 20.
Chaparro M, Garre A, Ricart E, Iborra M, Mesonero F, Vera I, Riestra S, García-Sánchez V, Luisa De Castro M, Martin-Cardona A, Aldeguer X, Mínguez M, de-Acosta MB, Rivero M, Muñoz F, Andreu M, Bargalló A, González-Muñoza C, Pérez Calle JL, García-Sepulcre MF, Bermejo F, Huguet JM, Cabriada JL, Gutiérrez A, Mañosa M, Villoria A, Carbajo AY, Lorente R, García-López S, Piqueras M, Hinojosa E, Arajol C, Sicilia B, Conesa AM, Sainz E, Almela P, Llaó J, Roncero O, Camo P, Taxonera C, Domselaar MV, Pajares R, Legido J, Madrigal R, Lucendo AJ, Alcaín G, Doménech E, Gisbert JP; GETECCU study group. Short and long-term effectiveness and safety of vedolizumab in inflammatory bowel disease: results from the ENEIDA registry. Aliment Pharmacol Ther. 2018 Oct;48(8):839-851. doi: 10.1111/apt.14930.

Layout table for additonal information
Responsible Party: Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
ClinicalTrials.gov Identifier: NCT05313620    
Other Study ID Numbers: GIS-2021-JAKihemo
First Posted: April 6, 2022    Key Record Dates
Last Update Posted: August 3, 2022
Last Verified: August 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Fundación de Investigación Biomédica - Hospital Universitario de La Princesa:
ulcerative colitis
Tromboembolism
Coagulation
Platelet Function
Tofacitinib
JAK inhibitors
anti-TNF
Infliximab
Adalimumab
Golimumab
Additional relevant MeSH terms:
Layout table for MeSH terms
Colitis
Colitis, Ulcerative
Thromboembolism
Ulcer
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Pathologic Processes
Inflammatory Bowel Diseases
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Adalimumab
Golimumab
Infliximab
Tofacitinib
Anti-Inflammatory Agents
Antirheumatic Agents
Dermatologic Agents
Gastrointestinal Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Tumor Necrosis Factor Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs