drugset / Trial / NCT04169828
The Ondansetron Premedication Trial in Juvenile Idiopathic Arthritis
Completed
52 enrolled
University of British Columbia
Alberta Children's Hospital · collabLondon Health Sciences Centre · collabMcGill University Health Centre/Research Institute of the McGill University Health Centre · collabMcMaster Children's Hospital · collabMcMaster University · collabThe Arthritis Society, Canada · collabThe Hospital for Sick Children · collabUniversity of Calgary · collabUniversity of Manitoba · collabUniversité de Montréal · collab
RandomizedParallel-groupOpen-labelTreatment
Summary
Far too many kids and families live in dread over the weekly nausea and vomiting caused by methotrexate - a medicine that controls joint swelling in Juvenile Arthritis patients. If methotrexate is not tolerated, expensive alternative biological medications may be started. This registry-based pragmatic randomized controlled trial will evaluate if routine premedication with the anti-emetic drug Ondansetron, reduces nausea and vomiting and increases the proportion of children able to continue methotrexate. By preventing nausea before it starts, the investigators hope to give kids and families a better quality of life and see a more cost-effective use of medication.
Timeline
- Start
- 2019-08-02
- Primary completion
- 2025-01-17
- Completion
- 2025-01-17
Publications
- Background Petty RE, Southwood TR, Manners P, Baum J, Glass DN, Goldenberg J, He X, Maldonado-Cocco J, Orozco-Alcala J, Prieur AM, Suarez-Almazor ME, Woo P; International League of Associations for Rheumatology. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol. 2004 Feb;31(2):390-2. No abstract available.
- Background Shiff NJ, Lix LM, Joseph L, Duffy C, Tucker LB, Svenson LW, Belisle P, Bernatsky S. The prevalence of systemic autoimmune rheumatic diseases in Canadian pediatric populations: administrative database estimates. Rheumatol Int. 2015 Mar;35(3):569-73. doi: 10.1007/s00296-014-3136-6. Epub 2014 Sep 26.
- Background ANSELL BM, BYWATERS EG. RHEUMATOID ARTHRITIS (STILL'S DISEASE). Pediatr Clin North Am. 1963 Nov;10:921-39. doi: 10.1016/s0031-3955(16)31475-4. No abstract available.
- Background Giannini EH, Brewer EJ, Kuzmina N, Shaikov A, Maximov A, Vorontsov I, Fink CW, Newman AJ, Cassidy JT, Zemel LS. Methotrexate in resistant juvenile rheumatoid arthritis. Results of the U.S.A.-U.S.S.R. double-blind, placebo-controlled trial. The Pediatric Rheumatology Collaborative Study Group and The Cooperative Children's Study Group. N Engl J Med. 1992 Apr 16;326(16):1043-9. doi: 10.1056/NEJM199204163261602.
- Background Beukelman T, Patkar NM, Saag KG, Tolleson-Rinehart S, Cron RQ, DeWitt EM, Ilowite NT, Kimura Y, Laxer RM, Lovell DJ, Martini A, Rabinovich CE, Ruperto N. 2011 American College of Rheumatology recommendations for the treatment of juvenile idiopathic arthritis: initiation and safety monitoring of therapeutic agents for the treatment of arthritis and systemic features. Arthritis Care Res (Hoboken). 2011 Apr;63(4):465-82. doi: 10.1002/acr.20460.
- Background Guzman J, Oen K, Tucker LB, Huber AM, Shiff N, Boire G, Scuccimarri R, Berard R, Tse SM, Morishita K, Stringer E, Johnson N, Levy DM, Duffy KW, Cabral DA, Rosenberg AM, Larche M, Dancey P, Petty RE, Laxer RM, Silverman E, Miettunen P, Chetaille AL, Haddad E, Houghton K, Spiegel L, Turvey SE, Schmeling H, Lang B, Ellsworth J, Ramsey S, Bruns A, Campillo S, Benseler S, Chedeville G, Schneider R, Yeung R, Duffy CM; ReACCh-Out investigators. The outcomes of juvenile idiopathic arthritis in children managed with contemporary treatments: results from the ReACCh-Out cohort. Ann Rheum Dis. 2015 Oct;74(10):1854-60. doi: 10.1136/annrheumdis-2014-205372. Epub 2014 May 19.
- Background Falvey S, Shipman L, Ilowite N, Beukelman T. Methotrexate-induced nausea in the treatment of juvenile idiopathic arthritis. Pediatr Rheumatol Online J. 2017 Jun 19;15(1):52. doi: 10.1186/s12969-017-0180-2.
- Background Bulatovic M, Heijstek MW, Verkaaik M, van Dijkhuizen EH, Armbrust W, Hoppenreijs EP, Kamphuis S, Kuis W, Egberts TC, Sinnema G, Rademaker CM, Wulffraat NM. High prevalence of methotrexate intolerance in juvenile idiopathic arthritis: development and validation of a methotrexate intolerance severity score. Arthritis Rheum. 2011 Jul;63(7):2007-13. doi: 10.1002/art.30367.
- Background Dupont-Lucas C, Grandjean-Blanchet C, Leduc B, Tripcovici M, Larocque C, Gervais F, Jantchou P, Amre D, Deslandres C. Prevalence and Risk Factors for Symptoms of Methotrexate Intolerance in Pediatric Inflammatory Bowel Disease. Inflamm Bowel Dis. 2017 Feb;23(2):298-303. doi: 10.1097/MIB.0000000000001014.
- Background Mulligan K, Wedderburn LR, Newman S. The experience of taking methotrexate for juvenile idiopathic arthritis: results of a cross-sectional survey with children and young people. Pediatr Rheumatol Online J. 2015 Dec 12;13:58. doi: 10.1186/s12969-015-0052-6.
- Background van Dijkhuizen EH, Bulatovic Calasan M, Pluijm SM, de Rotte MC, Vastert SJ, Kamphuis S, de Jonge R, Wulffraat NM. Prediction of methotrexate intolerance in juvenile idiopathic arthritis: a prospective, observational cohort study. Pediatr Rheumatol Online J. 2015 Feb 18;13:5. doi: 10.1186/s12969-015-0002-3. eCollection 2015.
- Background Bechard MA, Lemieux JR, Roth J, Watanabe Duffy K, Duffy CM, Aglipay MO, Jurencak R. Procedural pain and patient-reported side effects with weekly injections of subcutaneous methotrexate in children with rheumatic disorders. Pediatr Rheumatol Online J. 2014 Dec 19;12:54. doi: 10.1186/1546-0096-12-54. eCollection 2014.
- Background Klotsche J, Minden K, Niewerth M, Horneff G. Time spent in inactive disease before MTX withdrawal is relevant with regard to the flare risk in patients with JIA. Ann Rheum Dis. 2018 Jul;77(7):996-1002. doi: 10.1136/annrheumdis-2017-211968. Epub 2018 Feb 16.
- Background Scheuern A, Tyrrell PN, Haas JP, Hugle B. Countermeasures against methotrexate intolerance in juvenile idiopathic arthritis instituted by parents show no effect. Rheumatology (Oxford). 2017 Jun 1;56(6):901-906. doi: 10.1093/rheumatology/kew507.
- Background Schoemaker CG, van Dijkhuizen EHP, Vastert SJ. Contradictory and weak evidence on the effectiveness of anti-emetics for MTX-intolerance in JIA-patients. Pediatr Rheumatol Online J. 2018 Feb 15;16(1):13. doi: 10.1186/s12969-018-0229-x. No abstract available.
- Background Phillips RS, Friend AJ, Gibson F, Houghton E, Gopaul S, Craig JV, Pizer B. Antiemetic medication for prevention and treatment of chemotherapy-induced nausea and vomiting in childhood. Cochrane Database Syst Rev. 2016 Feb 2;2(2):CD007786. doi: 10.1002/14651858.CD007786.pub3.
- Background Cubeddu LX, Hoffmann IS, Fuenmayor NT, Finn AL. Efficacy of ondansetron (GR 38032F) and the role of serotonin in cisplatin-induced nausea and vomiting. N Engl J Med. 1990 Mar 22;322(12):810-6. doi: 10.1056/NEJM199003223221204.
- Background De Mulder PH, Seynaeve C, Vermorken JB, van Liessum PA, Mols-Jevdevic S, Allman EL, Beranek P, Verweij J. Ondansetron compared with high-dose metoclopramide in prophylaxis of acute and delayed cisplatin-induced nausea and vomiting. A multicenter, randomized, double-blind, crossover study. Ann Intern Med. 1990 Dec 1;113(11):834-40. doi: 10.7326/0003-4819-113-11-834.
- Background Dick GS, Meller ST, Pinkerton CR. Randomised comparison of ondansetron and metoclopramide plus dexamethasone for chemotherapy induced emesis. Arch Dis Child. 1995 Sep;73(3):243-5. doi: 10.1136/adc.73.3.243.
- Background Kempinska A, Benchimol EI, Mack A, Barkey J, Boland M, Mack DR. Short-course ondansetron for the prevention of methotrexate-induced nausea in children with Crohn disease. J Pediatr Gastroenterol Nutr. 2011 Oct;53(4):389-93. doi: 10.1097/MPG.0b013e31822855e7.
- Background Blanco R, Gonzalez-Gay MA, Garcia-Porrua C, Ibanez D, Garcia-Pais MJ, Sanchez-Andrade A, Vazquez-Caruncho M. Ondansetron prevents refractory and severe methotrexate-induced nausea in rheumatoid arthritis. Br J Rheumatol. 1998 May;37(5):590-2. doi: 10.1093/rheumatology/37.5.590. No abstract available.
- Background Cubeddu LX, Pendergrass K, Ryan T, York M, Burton G, Meshad M, Galvin D, Ciociola AA. Efficacy of oral ondansetron, a selective antagonist of 5-HT3 receptors, in the treatment of nausea and vomiting associated with cyclophosphamide-based chemotherapies. Ondansetron Study Group. Am J Clin Oncol. 1994 Apr;17(2):137-46. doi: 10.1097/00000421-199404000-00010.
- Background Silverman E, Mouy R, Spiegel L, Jung LK, Saurenmann RK, Lahdenne P, Horneff G, Calvo I, Szer IS, Simpson K, Stewart JA, Strand V; Leflunomide in Juvenile Rheumatoid Arthritis (JRA) Investigator Group. Leflunomide or methotrexate for juvenile rheumatoid arthritis. N Engl J Med. 2005 Apr 21;352(16):1655-66. doi: 10.1056/NEJMoa041810.
- Background Ford I, Norrie J. Pragmatic Trials. N Engl J Med. 2016 Aug 4;375(5):454-63. doi: 10.1056/NEJMra1510059. No abstract available.
- Background Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009 Apr;42(2):377-81. doi: 10.1016/j.jbi.2008.08.010. Epub 2008 Sep 30.
- Background Bhatt DL, Mehta C. Adaptive Designs for Clinical Trials. N Engl J Med. 2016 Jul 7;375(1):65-74. doi: 10.1056/NEJMra1510061. No abstract available.
- Background Efird J. Blocked randomization with randomly selected block sizes. Int J Environ Res Public Health. 2011 Jan;8(1):15-20. doi: 10.3390/ijerph8010015. Epub 2010 Dec 23.
- Background Chausset A, Fargeix T, Pereira B, Echaubard S, Duquesne A, Desjonqueres M, Freychet C, Belot A, Merlin E. MISS questionnaire in French version: a good tool for children and parents to assess methotrexate intolerance. Clin Rheumatol. 2017 Jun;36(6):1281-1288. doi: 10.1007/s10067-017-3638-1. Epub 2017 May 5.
- Background Wallace CA, Giannini EH, Huang B, Itert L, Ruperto N; Childhood Arthritis Rheumatology Research Alliance; Pediatric Rheumatology Collaborative Study Group; Paediatric Rheumatology International Trials Organisation. American College of Rheumatology provisional criteria for defining clinical inactive disease in select categories of juvenile idiopathic arthritis. Arthritis Care Res (Hoboken). 2011 Jul;63(7):929-36. doi: 10.1002/acr.20497.
- Background Feldman BM, Grundland B, McCullough L, Wright V. Distinction of quality of life, health related quality of life, and health status in children referred for rheumatologic care. J Rheumatol. 2000 Jan;27(1):226-33.
- Background Otto C, Barthel D, Klasen F, Nolte S, Rose M, Meyrose AK, Klein M, Thyen U, Ravens-Sieberer U. Predictors of self-reported health-related quality of life according to the EQ-5D-Y in chronically ill children and adolescents with asthma, diabetes, and juvenile arthritis: longitudinal results. Qual Life Res. 2018 Apr;27(4):879-890. doi: 10.1007/s11136-017-1753-8. Epub 2017 Nov 30.
- Background Schoenfeld DA. A simple algorithm for designing group sequential clinical trials. Biometrics. 2001 Sep;57(3):972-4. doi: 10.1111/j.0006-341x.2001.00972.x.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Ondansetron | Other / unclassified | 2 mg | Oral |
| Subject | Ondansetron | Other / unclassified | 4 mg | Oral |
| Subject | Ondansetron | Other / unclassified | 8 mg | Oral |
| Background | Folic/folinic acid | Unknown | — | — |
| Background | Methotrexate | Small molecule | — | — |