The Ondansetron Premedication Trial in Juvenile Idiopathic Arthritis
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 52
- 试验地点
- 11
- 主要终点
- Proportion of subjects that remain on methotrexate with no intolerance
研究概览
简要总结
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.
详细描述
- Purpose:
To evaluate if routine pre-medication with the anti-emetic ondansetron reduces methotrexate intolerance and increases the proportion of children with JIA able to continue taking methotrexate, resulting in a better quality of life and more cost-effective medication use. 2. Hypothesis:
Prophylactic prescription of ondansetron with methotrexate will increase the proportion of children that remain on methotrexate and intolerance free one year after starting methotrexate, relative to prescription of ondansetron after intolerance symptoms develop. 3. Justification:
Methotrexate intolerance is thought to be largely the result of Pavlovian conditioning secondary to previous exposure and symptoms can be triggered by associated stimuli, such as a yellow liquid similar in color to methotrexate or the smell of alcohol cleansing swabs. This intolerance leads to poor adherence to optimal dosing or to stopping the medication altogether. Children who cannot adhere to optimal dosing or stop methotrexate may require expensive biologic medications to control their JIA. Methotrexate intolerance often leads to use of anti-emetic medications which, unfortunately, rarely reverse conditioned responses. In oncology anti-emetics are used prophylactically as premedication in all subjects receiving chemotherapy to prevent the establishment of conditioned intolerance.
By conducting a registry-based pragmatic adaptive superiority randomized clinical trial the investigators will include most subjects in whom the treatment may be used under the usual conditions of practice to demonstrate effectiveness under real word circumstances. Patients enrolled in a pragmatic trial are more representative because eligibility criteria are less strict. More so, a registry-based pragmatic RCT can also be much cheaper than a traditional RCT. 4. Objectives:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 4 Years 至 16 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ages 4-16 years
- •Diagnosis of JIA as per ILAR criteria [1], irrespective of JIA category
- •Followed at a CAPRI centre in Canada
- •Starting methotrexate to control JIA manifestations (arthritis, uveitis, psoriasis). (Female subjects of child bearing potential who are taking methotrexate for JIA cannot be pregnant, breastfeeding, or planning a pregnancy while on the drug and females of childbearing potential who are sexually active must use highly effective medically acceptable contraception. Subjects who stop methotrexate during the study will also discontinue ondansetron.)
- •Informed written consent to participate
- •Participating in the CAPRI JIA Registry
排除标准
- •Previous use of methotrexate
- •Known hypersensitivity to ondansetron or any components of its formulations
- •Known hypersensitivity to other 5-HT3 antagonists
- •Known congenital Long-QT syndrome
- •Patients taking other medicinal products that lead to either QT prolongation or electrolyte abnormalities
- •Because the serotonin syndrome may occur when ondansetron is combined with other agents that may affect the serotonergic neurotransmitter system, patients receiving any of the serotonergic and/or neuroleptic drugs listed below will be excluded:
- •Triptans, SSRIs, SNRIs, lithium, sibutramine, fentanyl and its analogues, dextromethorphan, tramadol, tapendalol, meperidine, methadone, pentazocine or St. John's Wort (Hypericum perforatum), MAOIs, linezolid, methylene blue.
- •Patients who are pregnant or breastfeeding, or are sexually active and unwilling to practice an acceptable method of birth control.
- •Family unable to complete questionnaires in English or French
研究组 & 干预措施
Ondansetron premedication
Methotrexate and folic/folinic acid as prescribed by physician. Ondansetron: 2 mg if <15Kg, 4 mg if 15-30Kg, 8 mg if >30Kg to be taken by mouth one hour before each weekly methotrexate dose, followed by two additional doses every 6-8 hours if awake. To be started from the very first dose of methotrexate.
干预措施: Methotrexate (Drug)
Ondansetron premedication
Methotrexate and folic/folinic acid as prescribed by physician. Ondansetron: 2 mg if <15Kg, 4 mg if 15-30Kg, 8 mg if >30Kg to be taken by mouth one hour before each weekly methotrexate dose, followed by two additional doses every 6-8 hours if awake. To be started from the very first dose of methotrexate.
干预措施: Ondansetron (Drug)
Ondansetron premedication
Methotrexate and folic/folinic acid as prescribed by physician. Ondansetron: 2 mg if <15Kg, 4 mg if 15-30Kg, 8 mg if >30Kg to be taken by mouth one hour before each weekly methotrexate dose, followed by two additional doses every 6-8 hours if awake. To be started from the very first dose of methotrexate.
干预措施: Folic/folinic acid (Drug)
Ondansetron as needed
Methotrexate and folic/folinic acid as prescribed by physician. ONLY children who report nausea/vomiting during regular care will be prescribed ondansetron at the same dose as in experimental group (2 mg if <15Kg, 4 mg if 15-30Kg, 8 mg if >30Kg to be taken by mouth one hour before each weekly methotrexate dose, followed by two additional doses every 6-8 hours if awake), as per the attending rheumatologist's discretion
干预措施: Methotrexate (Drug)
Ondansetron as needed
Methotrexate and folic/folinic acid as prescribed by physician. ONLY children who report nausea/vomiting during regular care will be prescribed ondansetron at the same dose as in experimental group (2 mg if <15Kg, 4 mg if 15-30Kg, 8 mg if >30Kg to be taken by mouth one hour before each weekly methotrexate dose, followed by two additional doses every 6-8 hours if awake), as per the attending rheumatologist's discretion
干预措施: Ondansetron (Drug)
Ondansetron as needed
Methotrexate and folic/folinic acid as prescribed by physician. ONLY children who report nausea/vomiting during regular care will be prescribed ondansetron at the same dose as in experimental group (2 mg if <15Kg, 4 mg if 15-30Kg, 8 mg if >30Kg to be taken by mouth one hour before each weekly methotrexate dose, followed by two additional doses every 6-8 hours if awake), as per the attending rheumatologist's discretion
干预措施: Folic/folinic acid (Drug)
结局指标
主要结局
Proportion of subjects that remain on methotrexate with no intolerance
时间窗: One year after starting methotrexate.
Intolerance will be defined as ≥6 points in the English or French versions of the validated Methotrexate Intolerance Severity Score, MISS \[10, 36\]. Scores in the MISS questionaire go from 0 (no signs of intolerance) to a maximum of 36 (all signs of intolerance are severe). The MISS questionnaire takes less than 2 minutes to complete (see Appendix). It will be added to the Registry questionnaires completed by families online or on paper as per the CAPRI Centre usual Registry procedures.
次要结局
- Frequency and cumulative incidence of adverse events (safety and tolerability)(Within one year)
- Methotrexate intolerance(Within one year)
- Attainment of inactive disease(Within one year)
- Starting a biologic medication(Within one year)
- Quality of My Life scale(4-8 months after starting methotrexate)
- MISS questionnaire(4-8 months after starting methotrexate)
研究者
Jaime Guzman
Principle Investigator
University of British Columbia