Predicting Response to Standardized Pediatric Colitis Therapy (PROTECT)
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|ClinicalTrials.gov Identifier: NCT01536535|
Recruitment Status : Completed
First Posted : February 22, 2012
Last Update Posted : October 4, 2018
This is a multi-center, open-label study to determine the safety and effectiveness (how well it works) of two standardized treatments called "mesalamine" (Pentasa®) and "prednisone" in children with newly diagnosed UC. Standardized treatments are types of treatments agreed upon and used by many qualified doctors. The medications being used in this study are considered "standard of care". Currently the ways in which these medicines are used (doses, frequency of dosing) may vary from site to site. This study will determine response to a standardized way of giving these medicines.
This study will also identify biomarkers for ulcerative colitis. Biomarkers are things that doctors can find in blood, stool, or bowel tissue that indicate how much inflammation there is in the bowel, how the inflammation is produced, and whether the inflammation is responding to treatment. Collecting response and remission (free of symptoms) information on these standardized treatments and the "biomarkers" can possibly help doctors create a model, or plan to know which children with UC may respond quickly, or which children may develop complications.
|Condition or disease||Intervention/treatment||Phase|
|Ulcerative Colitis||Drug: Mesalamine Drug: Corticosteroid Drug: Corticosteroids then mesalamine||Phase 4|
Ulcerative Colitis (UC) denotes a phenotype of chronic inflammatory bowel disease (IBD), where inflammation is localized to the colonic mucosa, and extends from the rectum proximally in varying extents. The disorder is thought to result from an inappropriate activation of the mucosal immune system by antigens derived from both the host epithelium and the enteric flora, in genetically susceptible individuals. UC is strikingly heterogeneous with respect to age of onset, anatomical extent and disease course, with some experiencing chronically active severe disease, while others have intermittent periods of clinical remission and disease exacerbation. Patients' therapeutic responses vary. The reasons underlying such variability are not well understood. Although it has been widely hypothesized that several genes may influence the development of UC, and modify its phenotypic expression and severity, to date there are few confirmed examples of such relationships.
It has been postulated that the 5-aminosalicylate drugs exert their anti-inflammatory effect locally at the intestinal mucosa. Mechanisms likely include inhibition of 5-lipoxygenase resulting in decreased production of leukotriene B4, scavenging of reactive oxygen metabolites, prevention of up-regulation of leukocyte adhesion molecules, and inhibition of IL-1 synthesis. Though multiple studies have shown the efficacy of aminosalicylates in inducing and maintaining remission in adults with UC, there are few data in children.
Corticosteroids have been the mainstay of treatment of severe UC since efficacy was first demonstrated in the 1955 randomized controlled trial by Truelove and Witts. Recent practice guidelines developed in adults support their use because of rapid onset of action and significant efficacy though CS dependency is noted. Though no controlled data on their use have been reported in children they are frequently used in this population. A recent report from investigators leading the prospective Pediatric IBD Collaborative Research Group Registry described 97 subjects with a diagnosis of UC and a minimum of 1 year follow-up; 79% received CS. At diagnosis 81% of CS treated patients had moderate/severe disease, and 81% had pancolitis. Clinically inactive disease, determined by physician global assessment, was noted in 60% at 3 months following CS therapy, but by one year 45% were considered CS dependent despite the frequent use of IM. Among those children with initially moderate to severe disease in clinical remission at 3 months, about two-thirds had stopped the CS by one year.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||467 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Multicenter Open-label Study Evaluating the Safety and Efficacy of Standardized Initial Therapy Using Either Mesalamine or Corticosteroids Then Mesalamine to Treat Children and Adolescents With Newly Diagnosed Ulcerative Colitis.|
|Actual Study Start Date :||May 1, 2012|
|Actual Primary Completion Date :||April 30, 2018|
|Actual Study Completion Date :||April 30, 2018|
Experimental: Mesalamine Only
mesalamine (Pentasa®) comes in 500mg capsules, and doses will need to be rounded to the nearest 500mg increment, with a maximum dose of 76 mg/kg/day. The average dose for the pediatric population will be approximately 70 mg/kg/day. Patients will be allowed to escalate to the final dose over 4 days to minimize sideeffects such as headache.
If a patient does not respond to mesalamine then a corticosteroid will be added to the treatment.
Mesalamine (Pentasa) comes in 500mg capsules, and doses will need to be rounded to the nearest 500mg increment, with a maximum dose of 76 mg/kg/day. The average dose for the pediatric population will be approximately 70 mg/kg/day. Patients will be allowed to escalate to the final dose over 4 days to minimize side-effects such as headache.
Other Name: Pentasa
Experimental: Corticosteroids then mesalamine
Patients will begin with Corticosteroids, which will be weaned as tolerated and mesalamine (Pentasa®) added.
Drug: Corticosteroids then mesalamine
Initiate treatment with prednisone, 1-1.5 mg/kg/day, (maximum 40-60 mg in a single morning dose, either as tablet or liquid equivalent), rounded up to the nearest 5 mg value. This dose will be continued for 2 weeks to assess response. If response mesalamine will be added 500 mg capsules 70-75 mg/kg per day
Other Name: Prednisone
Active Comparator: Corticosteriod
Hospitalized patients with severe UC (PUCAI≥65) will begin IV Corticosteroids followed by a corticosteroid taper.
Initiate treatment with IV Corticosteroid followed by corticosteroid taper for patients hospitalized with severe CS.
Other Name: Prednisone
- Corticosteroid free remission (SFR) [ Time Frame: 52 weeks ]Relative to other patients, those who have a PUCAI<10 at 4 weeks from start of therapy will be more likely to be in corticosteroid free remission (PUCAI<10) at 52 weeks while receiving the aminosalicylate mesalamine only as maintenance therapy without the need for rescue therapy with IM, CI, anti-TNFα, or surgery.
- Corticosteroid free remission [ Time Frame: 52 weeks ]
The secondary endpoints are defined relative to start of therapy:
- PUCAI <10 at 4 weeks
- SFR at 12 weeks without the need for rescue therapy
- SFR at 26 weeks without the need for rescue therapy
- SFR at 104 weeks without the need for rescue therapy
- Endoscopic response (Mayo score reduced by ≥1) and being 0,1 at week 52
- Endoscopic remission (Mayo score 0) at week 52
- IMPACT - III at 52 and 104 weeks
- Colectomy free status during the follow-up period
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): NCT01536535
Show 29 Study Locations
|Principal Investigator:||Jeffrey Hyams, MD||Connecticut Children's Medical Center|
|Principal Investigator:||Lee Denson, MD||Children's Hospital Medical Center, Cincinnati|
|Principal Investigator:||Sonia Davis, DrPH||Collaborative Studies Coordinating Center - UNC-CH|