Infliximab Accelerated Induction in Moderate to Severe Pediatric UC
关键词
抽象
描述
General intervention scheme:
The decision to start IFX is the sole decision of the treating physician based on the patient's immediate need. Eligible patients are those who are planned to start IFX. All patients will undergo clinical and laboratory evaluation for IFX eligibility (PPD, infectious serology). If the tests have already done in the last 3 months, we will use these data, there is no need to repeat. Patients must have a negative stool culture, stool for parasites and clostridium difficile toxin test performed over the last week in order to be eligible. The screening visit may be performed concomitantly with the enrolment visit if all inclusion and exclusion criteria are met.
Patients will be enrolled at the first screening visit. Informed consent will be signed by both parents is required during enrollment. Informed assent will be offered for patients 14 years old and older. Eligible patients, ambulatory UC patients, requiring IFX for corticosteroid dependent or refractory moderate to severe disease (excluding acute severe UC), meeting inclusion/exclusion criteria, after obtaining informed consent, will be randomized (1:1 ratio in blocks of four, stratified by immunomodulators use) at enrollment visit (week 0, prior to IFX initiation) to either group 1 or group 2 using opaque, numbered and sealed envelopes. Prior corticosteroid treatment is allowed as a taper-down schedule during induction with IFX and must be terminated by week 10 (otherwise will be defined as induction failure). At each visit all patients will be examined and have height, weight, and PUCAI performed as well as comprehensive laboratory examinations including CBC, albumin, AST, ALT, ESR and CRP (CRP will be measured and registered in mg/dL) and fecal samples (4 grams) for bile acids and microbiome/virome. Fecal sample for fecal calprotectin (FC) will be obtained as well at weeks 20 and 52. Extent of disease will be registered using the Paris classification (Levine A et al, IBD, June 2011) and will be based on the latest colonoscopic evaluation (described only by macroscopic involvement). Patients who undergo a colonoscopy at any time as standard of care before initiating biologic therapy should register the results of colonoscopy (according to the Mayo score- A score of ≤1 is considered complete mucosal healing). In addition, every colonoscopy that will be performed during the study period based on physician discretion, should be register in the CRF (Colonoscopy is not part of this specific protocol).
The study period is composed of two distinctive phases: Intervention phase: week 0-20 and follow-up phase: week 21-52.
Group 1 (intervention group): Patients in group 1 will receive an accelerated induction at 0,1,3 weeks (5 mg/kg) and then at week 7,11,15.
Group 2 (control group): Patients in group 2 will receive a per protocol induction at 0,2,6 weeks (5 mg/kg) and then at week 14.
Intensification by shortening intervals between infusion rather than dose increment was chosen based on the pharmacokinetics of IFX in severe disease favoring this strategy in-order to maintain adequate trough drug-levels and avoid intermittent exposure (23).
Drug levels will be obtained prior to each infusion in each group in the intervention phase. Further maintenance will be planned according to drug levels at weeks 15 and 14, respectively. A visit concluding the intervention phase will be performed at week 20. The follow-up phase will continue without further interventions till week 52. During the follow-up phase (maintenance) treatment will be administered according to the treating physician discretion, with no restrictions.
Patients with induction failure in the control arm (defined as a lack of improvement of at least 20 points from the baseline PUCAI score OR PUCAI≥35 at 3 weeks following induction) will be able to undergo treatment intensification by decreasing infusion intervals according to the treating physician discretion.
日期
最后验证: | 08/31/2019 |
首次提交: | 06/30/2017 |
提交的预估入学人数: | 07/02/2017 |
首次发布: | 07/05/2017 |
上次提交的更新: | 09/16/2019 |
最近更新发布: | 09/17/2019 |
实际学习开始日期: | 04/15/2018 |
预计主要完成日期: | 11/30/2021 |
预计完成日期: | 03/31/2022 |
状况或疾病
干预/治疗
Drug: Infliximab
相
手臂组
臂 | 干预/治疗 |
---|---|
Experimental: Accelerated induction Patients in group 1 will receive an accelerated induction of infliximab at 0,1,3 weeks (5 mg/kg) and then at week 7,11,15. | |
Active Comparator: Per protocol Patients in group 2 will receive a per protocol induction of infliximab at 0,2,6 weeks (5 mg/kg) and then at week 14. |
资格标准
有资格学习的年龄 | 6 Years 至 6 Years |
有资格学习的性别 | All |
接受健康志愿者 | 是 |
标准 | Inclusion Criteria: 1. Ulcerative colitis 2. PUCAI≥35 3. Age: 6 - 17 years (inclusive) 4. Planned to initiate IFX therapy. 5. Naïve to biologics 6. Informed consent 7. Neg. PPD-Test, negative HBV- S Ag 8. Negative stool culture, parasites and clostridium toxin Exclusion Criteria: 1. Pregnancy. 2. Acute severe colitis. 3. Renal Failure. 4. Toxic megacolon. 5. Patients whose disease is confined to the rectum (i.e. proctitis). 6. Prior treatment with infliximab or adalimumab. 7. Previous malignancy. 8. Sepsis or active bacterial infection. 9. Known immune deficiency. 10. Positive Hepatitis B surface antigen or evidence for TB. 11. IBD unclassified. |
结果
主要结果指标
1. Clinical remission on infliximab [20 weeks]
次要成果指标
1. Colectomy free rate [52 weeks]
2. Clinical remission on infliximab [52 weeks]
3. Drug levels prior to last study infusion [14 weeks]
4. Calprotectin level [20 weeks]
5. Adverse events [20 weeks]