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

NCT05313620 | Recruiting Phase 4

• 1 other identifier: GIS-2021-JAKihemo
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Ulcerative Colitis; Thromboembolism

Keywords

ulcerative colitis; Tromboembolism; Coagulation; Platelet Function; Tofacitinib; JAK inhibitors; anti-TNF; Infliximab; Adalimumab; Golimumab

Outcome Measures

Primary Outcomes (1)

• platelet activation

  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

  1 year

Secondary Outcomes (3)

• Endoscopic activity

  1 year

• Endoscopic response

  1 year

• Endoscopic remission

  1 year

Study Arms (3)

Ulcerative colitis patients treated with tofacitinib

EXPERIMENTAL

Tofacitinib 5 mg/day oral per clinical practice

Drug: Tofacitinib

Ulcerative colitis patients treated with an anti-TNFα drug

ACTIVE COMPARATOR

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

healthy controls

NO INTERVENTION

Interventions

Tofacitinib DRUG

Tofacitinib 5 MG/day per clinical practice

Ulcerative colitis patients treated with tofacitinib

Infliximab Adalimumab y Golimumab 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 or golimumab (subcutaneus 50 mg milligram(s)-subcutaneus) per clinical practice.

Ulcerative colitis patients treated with an anti-TNFα drug

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Intrauterine device (IUD).
• Bilateral tubal occlusion.
• Couple with vasectomy.
• 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:

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fundación de Investigación Biomédica - Hospital Universitario de La Princesa: lead

Study Sites (1)

Hospital Universitario de La Princesa

Madrid, Madrid, 28006, Spain

RECRUITING

Related Publications (58)

• Ordas I, Eckmann L, Talamini M, Baumgart DC, Sandborn WJ. Ulcerative colitis. Lancet. 2012 Nov 3;380(9853):1606-19. doi: 10.1016/S0140-6736(12)60150-0. Epub 2012 Aug 20.

  PMID: 22914296 BACKGROUND

• Hoivik ML, Moum B, Solberg IC, Henriksen M, Cvancarova M, Bernklev T; IBSEN Group. Work disability in inflammatory bowel disease patients 10 years after disease onset: results from the IBSEN Study. Gut. 2013 Mar;62(3):368-75. doi: 10.1136/gutjnl-2012-302311. Epub 2012 Jun 20.

  PMID: 22717453 BACKGROUND

• Kornbluth A, Sachar DB; Practice Parameters Committee of the American College of Gastroenterology. Ulcerative colitis practice guidelines in adults: American College Of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol. 2010 Mar;105(3):501-23; quiz 524. doi: 10.1038/ajg.2009.727. Epub 2010 Jan 12.

  PMID: 20068560 BACKGROUND

• Ye Y, Pang Z, Chen W, Ju S, Zhou C. The epidemiology and risk factors of inflammatory bowel disease. Int J Clin Exp Med. 2015 Dec 15;8(12):22529-42. eCollection 2015.

  PMID: 26885239 BACKGROUND

• Ng SC, Shi HY, Hamidi N, Underwood FE, Tang W, Benchimol EI, Panaccione R, Ghosh S, Wu JCY, Chan FKL, Sung JJY, Kaplan GG. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet. 2017 Dec 23;390(10114):2769-2778. doi: 10.1016/S0140-6736(17)32448-0. Epub 2017 Oct 16.

  PMID: 29050646 BACKGROUND

• Burisch J, Pedersen N, Cukovic-Cavka S, Brinar M, Kaimakliotis I, Duricova D, Shonova O, Vind I, Avnstrom 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, Bjornsson E, Ragnarsson G, Bailey Y, Odes S, Schwartz D, Martinato M, Lupinacci G, Milla M, De Padova A, D'Inca 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.

  PMID: 23604131 BACKGROUND

• Chaparro M, Barreiro-de Acosta M, Benitez JM, Cabriada JL, Casanova MJ, Ceballos D, Esteve M, Fernandez H, Ginard D, Gomollon F, Lorente R, Nos P, Riestra S, Rivero M, Robledo P, Rodriguez C, Sicilia B, Torrella E, Garre A, Garcia-Esquinas E, Rodriguez-Artalejo F, Gisbert JP; EpidemIBD study group of GETECCU. EpidemIBD: rationale and design of a large-scale epidemiological study of inflammatory bowel disease in Spain. Therap Adv Gastroenterol. 2019 May 21;12:1756284819847034. doi: 10.1177/1756284819847034. eCollection 2019.

  PMID: 31205485 BACKGROUND

• Cohen RD, Yu AP, Wu EQ, Xie J, Mulani PM, Chao J. Systematic review: the costs of ulcerative colitis in Western countries. Aliment Pharmacol Ther. 2010 Apr;31(7):693-707. doi: 10.1111/j.1365-2036.2010.04234.x. Epub 2010 Jan 11.

  PMID: 20064142 BACKGROUND

• Ungaro R, Mehandru S, Allen PB, Peyrin-Biroulet L, Colombel JF. Ulcerative colitis. Lancet. 2017 Apr 29;389(10080):1756-1770. doi: 10.1016/S0140-6736(16)32126-2. Epub 2016 Dec 1.

  PMID: 27914657 BACKGROUND

• Chaparro M, Garre A, Ricart E, Iborra M, Mesonero F, Vera I, Riestra S, Garcia-Sanchez V, Luisa De Castro M, Martin-Cardona A, Aldeguer X, Minguez M, de-Acosta MB, Rivero M, Munoz F, Andreu M, Bargallo A, Gonzalez-Munoza C, Perez Calle JL, Garcia-Sepulcre MF, Bermejo F, Huguet JM, Cabriada JL, Gutierrez A, Manosa M, Villoria A, Carbajo AY, Lorente R, Garcia-Lopez S, Piqueras M, Hinojosa E, Arajol C, Sicilia B, Conesa AM, Sainz E, Almela P, Llao J, Roncero O, Camo P, Taxonera C, Domselaar MV, Pajares R, Legido J, Madrigal R, Lucendo AJ, Alcain G, Domenech 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.

  PMID: 30281832 BACKGROUND

• Sands BE, Sandborn WJ, Panaccione R, O'Brien CD, Zhang H, Johanns J, Adedokun OJ, Li K, Peyrin-Biroulet L, Van Assche G, Danese S, Targan S, Abreu MT, Hisamatsu T, Szapary P, Marano C; UNIFI Study Group. Ustekinumab as Induction and Maintenance Therapy for Ulcerative Colitis. N Engl J Med. 2019 Sep 26;381(13):1201-1214. doi: 10.1056/NEJMoa1900750.

  PMID: 31553833 BACKGROUND

• Ford AC, Sandborn WJ, Khan KJ, Hanauer SB, Talley NJ, Moayyedi P. Efficacy of biological therapies in inflammatory bowel disease: systematic review and meta-analysis. Am J Gastroenterol. 2011 Apr;106(4):644-59, quiz 660. doi: 10.1038/ajg.2011.73. Epub 2011 Mar 15.

  PMID: 21407183 BACKGROUND

• Danese S, Allez M, van Bodegraven AA, Dotan I, Gisbert JP, Hart A, Lakatos PL, Magro F, Peyrin-Biroulet L, Schreiber S, Tarabar D, Vavricka S, Halfvarson J, Vermeire S. Unmet Medical Needs in Ulcerative Colitis: An Expert Group Consensus. Dig Dis. 2019;37(4):266-283. doi: 10.1159/000496739. Epub 2019 Feb 6.

  PMID: 30726845 BACKGROUND

• Gordon JP, McEwan PC, Maguire A, Sugrue DM, Puelles J. Characterizing unmet medical need and the potential role of new biologic treatment options in patients with ulcerative colitis and Crohn's disease: a systematic review and clinician surveys. Eur J Gastroenterol Hepatol. 2015 Jul;27(7):804-12. doi: 10.1097/MEG.0000000000000378.

  PMID: 25933126 BACKGROUND

• Gisbert JP, Chaparro M. Predictors of Primary Response to Biologic Treatment [Anti-TNF, Vedolizumab, and Ustekinumab] in Patients With Inflammatory Bowel Disease: From Basic Science to Clinical Practice. J Crohns Colitis. 2020 Jun 19;14(5):694-709. doi: 10.1093/ecco-jcc/jjz195.

  PMID: 31777929 BACKGROUND

• Chaparro M, Garre A, Mesonero F, Rodriguez C, Barreiro-de Acosta M, Martinez-Cadilla J, Arroyo MT, Mancenido N, Sierra-Ausin M, Vera-Mendoza I, Casanova MJ, Nos P, Gonzalez-Munoza C, Martinez T, Bosca-Watts M, Calafat M, Busquets D, Girona E, Llao J, Martin-Arranz MD, Piqueras M, Ramos L, Suris G, Bermejo F, Carbajo AY, Casas-Deza D, Fernandez-Clotet A, Garcia MJ, Ginard D, Gutierrez-Casbas A, Hernandez L, Lucendo AJ, Marquez L, Merino-Ochoa O, Rancel FJ, Taxonera C, Lopez Sanroman A, Rubio S, Domenech E, Gisbert JP. Tofacitinib in Ulcerative Colitis: Real-world Evidence From the ENEIDA Registry. J Crohns Colitis. 2021 Jan 13;15(1):35-42. doi: 10.1093/ecco-jcc/jjaa145.

  PMID: 32969471 BACKGROUND

• Coskun M, Salem M, Pedersen J, Nielsen OH. Involvement of JAK/STAT signaling in the pathogenesis of inflammatory bowel disease. Pharmacol Res. 2013 Oct;76:1-8. doi: 10.1016/j.phrs.2013.06.007. Epub 2013 Jul 2.

  PMID: 23827161 BACKGROUND

• Sandborn WJ, Panes J, Sands BE, Reinisch W, Su C, Lawendy N, Koram N, Fan H, Jones TV, Modesto I, Quirk D, Danese S. Venous thromboembolic events in the tofacitinib ulcerative colitis clinical development programme. Aliment Pharmacol Ther. 2019 Nov;50(10):1068-1076. doi: 10.1111/apt.15514. Epub 2019 Oct 9.

  PMID: 31599001 BACKGROUND

• Scott IC, Hider SL, Scott DL. Thromboembolism with Janus Kinase (JAK) Inhibitors for Rheumatoid Arthritis: How Real is the Risk? Drug Saf. 2018 Jul;41(7):645-653. doi: 10.1007/s40264-018-0651-5.

  PMID: 29500799 BACKGROUND

• Sands BE, Sandborn WJ, Feagan BG, Lichtenstein GR, Zhang H, Strauss R, Szapary P, Johanns J, Panes J, Vermeire S, O'Brien CD, Yang Z, Bertelsen K, Marano C; Peficitinib-UC Study Group. Peficitinib, an Oral Janus Kinase Inhibitor, in Moderate-to-severe Ulcerative Colitis: Results From a Randomised, Phase 2 Study. J Crohns Colitis. 2018 Nov 9;12(10):1158-1169. doi: 10.1093/ecco-jcc/jjy085.

  PMID: 29917064 BACKGROUND

• van der Heijde D, Baraliakos X, Gensler LS, Maksymowych WP, Tseluyko V, Nadashkevich O, Abi-Saab W, Tasset C, Meuleners L, Besuyen R, Hendrikx T, Mozaffarian N, Liu K, Greer JM, Deodhar A, Landewe R. Efficacy and safety of filgotinib, a selective Janus kinase 1 inhibitor, in patients with active ankylosing spondylitis (TORTUGA): results from a randomised, placebo-controlled, phase 2 trial. Lancet. 2018 Dec 1;392(10162):2378-2387. doi: 10.1016/S0140-6736(18)32463-2. Epub 2018 Oct 22.

  PMID: 30360970 BACKGROUND

• Mesa RA, Vannucchi AM, Mead A, Egyed M, Szoke A, Suvorov A, Jakucs J, Perkins A, Prasad R, Mayer J, Demeter J, Ganly P, Singer JW, Zhou H, Dean JP, Te Boekhorst PA, Nangalia J, Kiladjian JJ, Harrison CN. Pacritinib versus best available therapy for the treatment of myelofibrosis irrespective of baseline cytopenias (PERSIST-1): an international, randomised, phase 3 trial. Lancet Haematol. 2017 May;4(5):e225-e236. doi: 10.1016/S2352-3026(17)30027-3. Epub 2017 Mar 20.

  PMID: 28336242 BACKGROUND

• Piran S, Schulman S. Management of venous thromboembolism: an update. Thromb J. 2016 Oct 4;14(Suppl 1):23. doi: 10.1186/s12959-016-0107-z. eCollection 2016.

  PMID: 27766049 BACKGROUND

• Kyrle PA, Rosendaal FR, Eichinger S. Risk assessment for recurrent venous thrombosis. Lancet. 2010 Dec 11;376(9757):2032-9. doi: 10.1016/S0140-6736(10)60962-2. Epub 2010 Dec 3.

  PMID: 21131039 BACKGROUND

• Danese S, Sans M, Fiocchi C. Inflammatory bowel disease: the role of environmental factors. Autoimmun Rev. 2004 Jul;3(5):394-400. doi: 10.1016/j.autrev.2004.03.002.

  PMID: 15288007 BACKGROUND

• Giannotta M, Tapete G, Emmi G, Silvestri E, Milla M. Thrombosis in inflammatory bowel diseases: what's the link? Thromb J. 2015 Apr 2;13:14. doi: 10.1186/s12959-015-0044-2. eCollection 2015.

  PMID: 25866483 BACKGROUND

• Montoro-Garcia S, Schindewolf M, Stanford S, Larsen OH, Thiele T. The Role of Platelets in Venous Thromboembolism. Semin Thromb Hemost. 2016 Apr;42(3):242-51. doi: 10.1055/s-0035-1570079. Epub 2016 Feb 29.

  PMID: 26926584 BACKGROUND

• Monroe DM, Hoffman M, Roberts HR. Platelets and thrombin generation. Arterioscler Thromb Vasc Biol. 2002 Sep 1;22(9):1381-9. doi: 10.1161/01.atv.0000031340.68494.34.

  PMID: 12231555 BACKGROUND

• Bergmeier W, Hynes RO. Extracellular matrix proteins in hemostasis and thrombosis. Cold Spring Harb Perspect Biol. 2012 Feb 1;4(2):a005132. doi: 10.1101/cshperspect.a005132.

  PMID: 21937733 BACKGROUND

• Fernandez-Bello I, Lopez-Longo FJ, Arias-Salgado EG, Jimenez-Yuste V, Butta NV. Behcet's disease: new insight into the relationship between procoagulant state, endothelial activation/damage and disease activity. Orphanet J Rare Dis. 2013 May 27;8:81. doi: 10.1186/1750-1172-8-81.

  PMID: 23711081 BACKGROUND

• Alvarez-Roman MT, Fernandez-Bello I, Jimenez-Yuste V, Martin-Salces M, Arias-Salgado EG, Rivas Pollmar MI, Justo Sanz R, Butta NV. Procoagulant profile in patients with immune thrombocytopenia. Br J Haematol. 2016 Dec;175(5):925-934. doi: 10.1111/bjh.14412. Epub 2016 Oct 21.

  PMID: 27766635 BACKGROUND

• Ozdemir ZC, Duzenli Kar Y, Gunduz E, Turhan AB, Bor O. Evaluation of hypercoagulability with rotational thromboelastometry in children with iron deficiency anemia. Hematology. 2018 Oct;23(9):664-668. doi: 10.1080/10245332.2018.1452456. Epub 2018 Mar 15.

  PMID: 29544395 BACKGROUND

• Coelho MC, Vieira Neto L, Kasuki L, Wildemberg LE, Santos CV, Castro G, Gouvea G, Veloso OC, Gadelha T, Gadelha MR. Rotation thromboelastometry and the hypercoagulable state in Cushing's syndrome. Clin Endocrinol (Oxf). 2014 Nov;81(5):657-64. doi: 10.1111/cen.12491. Epub 2014 Jun 12.

  PMID: 24815846 BACKGROUND

• Mulder MB, Proctor KG, Valle EJ, Livingstone AS, Nguyen DM, Van Haren RM. Hypercoagulability After Resection of Thoracic Malignancy: A Prospective Evaluation. World J Surg. 2019 Dec;43(12):3232-3238. doi: 10.1007/s00268-019-05123-7.

  PMID: 31407092 BACKGROUND

• Campello E, Spiezia L, Zabeo E, Maggiolo S, Vettor R, Simioni P. Hypercoagulability detected by whole blood thromboelastometry (ROTEM(R)) and impedance aggregometry (MULTIPLATE(R)) in obese patients. Thromb Res. 2015 Mar;135(3):548-53. doi: 10.1016/j.thromres.2015.01.003. Epub 2015 Jan 7.

  PMID: 25592651 BACKGROUND

• Bedreli S, Straub K, Achterfeld A, Willuweit K, Katsounas A, Saner F, Wedemeyer H, Herzer K. The Effect of Immunosuppression on Coagulation After Liver Transplantation. Liver Transpl. 2019 Jul;25(7):1054-1065. doi: 10.1002/lt.25476. Epub 2019 May 30.

  PMID: 31021493 BACKGROUND

• Grant AL, Letson HL, Morris JL, McEwen P, Hazratwala K, Wilkinson M, Dobson GP. Tranexamic acid is associated with selective increase in inflammatory markers following total knee arthroplasty (TKA): a pilot study. J Orthop Surg Res. 2018 Jun 18;13(1):149. doi: 10.1186/s13018-018-0855-5.

  PMID: 29914535 BACKGROUND

• Brophy DF, Martin EJ, Christian Barrett J, Nolte ME, Kuhn JG, Gerk PM, Carr ME, Pelzer H, Agerso H, Ezban M, Hedner U. Monitoring rFVIIa 90 mug kg(-)(1) dosing in haemophiliacs: comparing laboratory response using various whole blood assays over 6 h. Haemophilia. 2011 Sep;17(5):e949-57. doi: 10.1111/j.1365-2516.2011.02492.x. Epub 2011 Mar 1.

  PMID: 21362113 BACKGROUND

• Tsantes AE, Kyriakou E, Ikonomidis I, Katogiannis K, Papadakis I, Douramani P, Kopterides P, Kapsimali V, Lekakis J, Tsangaris I, Bonovas S. Comparative Assessment of the Anticoagulant Activity of Rivaroxaban and Dabigatran in Patients With Nonvalvular Atrial Fibrillation: A Noninterventional Study. Medicine (Baltimore). 2016 Apr;95(14):e3037. doi: 10.1097/MD.0000000000003037.

  PMID: 27057830 BACKGROUND

• Patel-Hett S, Martin EJ, Mohammed BM, Rakhe S, Sun P, Barrett JC, Nolte ME, Kuhn J, Pittman DD, Murphy JE, Brophy DF. Marstacimab, a tissue factor pathway inhibitor neutralizing antibody, improves coagulation parameters of ex vivo dosed haemophilic blood and plasmas. Haemophilia. 2019 Sep;25(5):797-806. doi: 10.1111/hae.13820. Epub 2019 Jul 23.

  PMID: 31336410 BACKGROUND

• Yada K, Nogami K, Ogiwara K, Shida Y, Furukawa S, Yaoi H, Takeyama M, Kasai R, Shima M. Global coagulation function assessed by rotational thromboelastometry predicts coagulation-steady state in individual hemophilia A patients receiving emicizumab prophylaxis. Int J Hematol. 2019 Oct;110(4):419-430. doi: 10.1007/s12185-019-02698-8. Epub 2019 Jun 28.

  PMID: 31254165 BACKGROUND

• Walden K, Shams Hakimi C, Jeppsson A, Karlsson M. Effects of fibrinogen supplementation on clot formation in blood samples from cardiac surgery patients before and after tranexamic acid administration. Transfus Med. 2019 Oct;29(5):319-324. doi: 10.1111/tme.12604. Epub 2019 May 22.

  PMID: 31115109 BACKGROUND

• Lillemae K, Laine AT, Schramko A, Niemi TT. Effect of Albumin in Combination With Mannitol on Whole-blood Coagulation In Vitro Assessed by Thromboelastometry. J Neurosurg Anesthesiol. 2018 Jul;30(3):265-272. doi: 10.1097/ANA.0000000000000438.

  PMID: 28498140 BACKGROUND

• Lak M, Scharling B, Blemings A, Sharifian R, Maleki Z, Daraee A, Arjmand AR, Hedner U. Evaluation of rFVIIa (NovoSeven) in Glanzmann patients with thromboelastogram. Haemophilia. 2008 Jan;14(1):103-10. doi: 10.1111/j.1365-2516.2007.01592.x. Epub 2007 Dec 7.

  PMID: 18070065 BACKGROUND

• Wang Y, Andrews M, Yang Y, Lang S, Jin JW, Cameron-Vendrig A, Zhu G, Reheman A, Ni H. Platelets in thrombosis and hemostasis: old topic with new mechanisms. Cardiovasc Hematol Disord Drug Targets. 2012 Dec;12(2):126-32. doi: 10.2174/1871529x11202020126.

  PMID: 23030445 BACKGROUND

• Berndt MC, Metharom P, Andrews RK. Primary haemostasis: newer insights. Haemophilia. 2014 May;20 Suppl 4:15-22. doi: 10.1111/hae.12427.

  PMID: 24762270 BACKGROUND

• Mackman N. Triggers, targets and treatments for thrombosis. Nature. 2008 Feb 21;451(7181):914-8. doi: 10.1038/nature06797.

  PMID: 18288180 BACKGROUND

• Gurbel PA, Bliden K, Barnett SD, Witt C, Zou H, Tantry U. An Ex Vivo Study to Evaluate the Effect of Tegaserod on Platelet Activation and Aggregation. J Cardiovasc Pharmacol Ther. 2021 Jan;26(1):40-50. doi: 10.1177/1074248420942004. Epub 2020 Jul 16.

  PMID: 32672062 BACKGROUND

• Meah MN, Raftis J, Wilson SJ, Perera V, Garonzik SM, Murthy B, Everlof JG, Aronson R, Luettgen J, Newby DE. Antithrombotic Effects of Combined PAR (Protease-Activated Receptor)-4 Antagonism and Factor Xa Inhibition. Arterioscler Thromb Vasc Biol. 2020 Nov;40(11):2678-2685. doi: 10.1161/ATVBAHA.120.314960. Epub 2020 Sep 10.

  PMID: 32907366 BACKGROUND

• Cirillo P, Taglialatela V, Pellegrino G, Morello A, Conte S, Di Serafino L, Cimmino G. Effects of colchicine on platelet aggregation in patients on dual antiplatelet therapy with aspirin and clopidogrel. J Thromb Thrombolysis. 2020 Aug;50(2):468-472. doi: 10.1007/s11239-020-02121-8.

  PMID: 32335777 BACKGROUND

• Alvarez Roman MT, Fernandez Bello I, Arias-Salgado EG, Rivas Pollmar MI, Jimenez Yuste V, Martin Salces M, Butta NV. Effects of thrombopoietin receptor agonists on procoagulant state in patients with immune thrombocytopenia. Thromb Haemost. 2014 Jul 3;112(1):65-72. doi: 10.1160/TH13-10-0873. Epub 2014 Feb 6.

  PMID: 24500066 BACKGROUND

• Lee J, Jung CW, Jeon Y, Kim TK, Cho YJ, Koo CH, Choi YH, Kim KB, Hwang HY, Kim HR, Park JY. Effects of preoperative aspirin on perioperative platelet activation and dysfunction in patients undergoing off-pump coronary artery bypass graft surgery: A prospective randomized study. PLoS One. 2017 Jul 17;12(7):e0180466. doi: 10.1371/journal.pone.0180466. eCollection 2017.

  PMID: 28715503 BACKGROUND

• Vrigkou E, Tsangaris I, Bonovas S, Kopterides P, Kyriakou E, Konstantonis D, Pappas A, Anthi A, Gialeraki A, Orfanos SE, Armaganidis A, Tsantes A. Platelet and coagulation disorders in newly diagnosed patients with pulmonary arterial hypertension. Platelets. 2019;30(5):646-651. doi: 10.1080/09537104.2018.1499890. Epub 2018 Jul 26.

  PMID: 30047809 BACKGROUND

• Peyrin-Biroulet L, Sandborn W, Sands BE, Reinisch W, Bemelman W, Bryant RV, D'Haens G, Dotan I, Dubinsky M, Feagan B, Fiorino G, Gearry R, Krishnareddy S, Lakatos PL, Loftus EV Jr, Marteau P, Munkholm P, Murdoch TB, Ordas I, Panaccione R, Riddell RH, Ruel J, Rubin DT, Samaan M, Siegel CA, Silverberg MS, Stoker J, Schreiber S, Travis S, Van Assche G, Danese S, Panes J, Bouguen G, O'Donnell S, Pariente B, Winer S, Hanauer S, Colombel JF. Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE): Determining Therapeutic Goals for Treat-to-Target. Am J Gastroenterol. 2015 Sep;110(9):1324-38. doi: 10.1038/ajg.2015.233. Epub 2015 Aug 25.

  PMID: 26303131 BACKGROUND

• Kamm MA, Sandborn WJ, Gassull M, Schreiber S, Jackowski L, Butler T, Lyne A, Stephenson D, Palmen M, Joseph RE. Once-daily, high-concentration MMX mesalamine in active ulcerative colitis. Gastroenterology. 2007 Jan;132(1):66-75; quiz 432-3. doi: 10.1053/j.gastro.2006.10.011. Epub 2006 Oct 12.

  PMID: 17241860 BACKGROUND

• Van Assche G, Sandborn WJ, Feagan BG, Salzberg BA, Silvers D, Monroe PS, Pandak WM, Anderson FH, Valentine JF, Wild GE, Geenen DJ, Sprague R, Targan SR, Rutgeerts P, Vexler V, Young D, Shames RS. Daclizumab, a humanised monoclonal antibody to the interleukin 2 receptor (CD25), for the treatment of moderately to severely active ulcerative colitis: a randomised, double blind, placebo controlled, dose ranging trial. Gut. 2006 Nov;55(11):1568-74. doi: 10.1136/gut.2005.089854. Epub 2006 Apr 7.

  PMID: 16603634 BACKGROUND

• D'Haens G, Feagan B, Colombel JF, Sandborn WJ, Reinisch W, Rutgeerts P, Carbonnel F, Mary JY, Danese S, Fedorak RN, Hanauer S, Lemann M; International Organization for Inflammatory Bowel Diseases (IOIBD) and the Clinical Trial Committee Clincom of the European Crohn's and Colitis Organisation (ECCO). Challenges to the design, execution, and analysis of randomized controlled trials for inflammatory bowel disease. Gastroenterology. 2012 Dec;143(6):1461-9. doi: 10.1053/j.gastro.2012.09.031. Epub 2012 Sep 20.

  PMID: 23000597 BACKGROUND

• Nunes T, Barreiro-de Acosta M, Nos P, Marin-Jimenez I, Bermejo F, Ceballos D, Iglesias E, Gomez-Senent S, Torres Y, Ponferrada A, Arevalo JA, Hernandez V, Calvet X, Ginard D, Monfort D, Chaparro M, Mancenido N, Dominguez-Antonaya M, Villalon C, Perez-Calle JL, Munoz C, Nunez H, Carpio D, Aramendiz R, Bujanda L, Estrada-Oncins S, Hermida C, Barrio J, Casis MB, Duenas-Sadornil MC, Fernandez L, Calvo-Cenizo MM, Botella B, de Francisco R, Ayala E, Sans M; RECLICU Study Group of GETECCU. Usefulness of oral beclometasone dipropionate in the treatment of active ulcerative colitis in clinical practice: the RECLICU Study. J Crohns Colitis. 2010 Dec;4(6):629-36. doi: 10.1016/j.crohns.2010.07.003.

  PMID: 21122572 BACKGROUND

MeSH Terms

Conditions

Colitis, Ulcerative; Thromboembolism; Thrombosis

Interventions

tofacitinib

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Central Study Contacts

Sandra Hermida

CONTACT

913093911; sandra.hermida.hlp@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 2, 2021
• First Posted: April 6, 2022
• Study Start: April 1, 2022
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: March 17, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)