Ulcerative ColitisPhase 4PROTECTNCT01536535
Predicting Response to Standardized Pediatric Colitis Therapy
A Phase 4 study testing Mesalazine, IV Corticosteroid and Oral Corticosteroids in people with Ulcerative Colitis, run by Connecticut Children's Medical Center at 29 sites in 2 countries.
Trial summary
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 Ulcerative Colitis (UC). Read more about this study
- Who is it for?
- Ages 4 to 17 years
- Conditions the study is for
- Ulcerative Colitis
- What is being tested?
- Mesalazine, IV Corticosteroid and Oral Corticosteroids
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 431 participants
- Where
- 29 sitesin 2 countries
- Study dates
- 10 Jul 2012to 30 Apr 2018
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Age ≥ 4years and ≤17 years at initiation of therapy (achieved 4th birthday, not yet 18th)
- Weight ≥15 kg
- New diagnosis of ulcerative colitis established by standard clinical, endoscopic, and histologic features at the PROTECT study site
- Colitis extending beyond the rectosigmoid (Paris classification E2, E3, or E4)[144]. If a patient is seriously ill and the clinician does not advance the colonoscope beyond the sigmoid colon but the clinical condition of the patient highly suggests more extensive disease then that patient is eligible for study.
- Disease activity by PUCAI of ≥10 at diagnosis
- No therapy previously initiated to treat the newly diagnosed ulcerative colitis
Show all 11Show fewer
- Stool culture negative for routine enteric pathogens (Salmonella, Shigella, Campylobacter, E. coli 0157:H7) and Clostridium difficile toxin. Recent successful treatment for Clostridium difficile does not exclude a patient if toxin now absent. However, the patient must be a minimum of 5 weeks from the time treatment was started at the time toxin is absent.
- Stool study negative for enteric parasites (ova and parasites)
- Parent/guardian consent and patient assent
- Ability to remain in follow-up for a minimum of one year from diagnosis
- Female patients of child bearing age must have a negative urine pregnancy test and practice acceptable contraception (e.g., abstinence, intramuscular or hormonal contraception, two barrier methods (e.g., condom, diaphragm, or spermicide), intrauterine device, verbal report of the partner with history of vasectomy, or be surgically sterile). All female patients of childbearing potential (post-menarche) will undergo urine pregnancy testing at screening and must not be lactating.
Who cannot join
- Clinical, endoscopic, radiologic, or histologic evidence suggesting Crohn's disease (CD) consistent with Paris and North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) criteria [144, 145]
- A previous diagnosis of inflammatory bowel disease for which treatment was given
- Evidence of any active enteric infection at the time of study entry
- Use of any oral CS for non-gastrointestinal indication within the past 4 weeks (e.g., asthma). Use of inhaled CS does not exclude a patient.
- History of use of IM or anti-TNFα agent for other medical conditions (e.g., juvenile rheumatoid arthritis) within the past 6 months
- Use of Accutane within the past 4 weeks
Show all 17Show fewer
- Use of any investigational drug within the past four weeks
- Use of any 5-aminosalicylate within the past 4 weeks
- Pregnancy
- Subjects with poorly controlled medical conditions (e.g. diabetes, congestive heart failure)
- Proctitis or proctosigmoiditis only (Paris classification E1) on colonoscopic evaluation
- Chronic renal disease (BUN and serum creatinine >1.5 times the upper normal limit)
- Hepatic disease (AST or Alkaline phosphatase (ALP) greater than 3 times the upper normal limit in the absence of concomitant liver disease associated with IBD following full evaluation)
- History of allergy or hypersensitivity to salicylates, aminosalicylates, or any component of the Pentasa capsule.
- History of coexisting chronic illness or evidence of significant organic or psychiatric disease on medical history or physical examination, which, in the Investigator's opinion, would prevent participation in the study
- History or presence of any condition causing malabsorption or an effect on gastrointestinal (GI) motility, or history of extensive small bowel resection (greater than half the length of the small intestine).
- The finding of Helicobacter pylori at the time of evaluation does not exclude the patient from the study. Whether to treat this patient for Helicobacter pylori and when will be left to the discretion of the site.
Trial locations and contacts
29 sites in 2 countries.
29 sites in 2 countries
United States26 sites
Emory Children's Center
Atlanta, Georgia, 30322
John Hopkins Children's Hospital
Baltimore, Maryland, 21287
Children's Hospital of Boston
Boston, Massachusetts, 02115
Women and Children's Hospital of Buffalo
Buffalo, New York, 14222
University of North Carolina at Chapel HIll
Chapel Hill, North Carolina, 27599
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611-2605
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Nationwide Children's Hospital
Columbus, Ohio, 43205
UT Southwestern
Dallas, Texas, 75235
Connecticut Children's Medical Center
Hartford, Connecticut, 06106
Riley Children's Hospital
Indianapolis, Indiana, 46202
Nemours Children's Clinic
Jacksonville, Florida, 32207
UCLA Medical Center
Los Angeles, California, 90095
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
University of Minnesota Medical Center
Minneapolis, Minnesota, 55454
Goryeb Children's Hospital / Atlantic Health
Morristown, New Jersey, 07962
Monroe Carell Jr. Children's Hospital at Vanderbilt
Nashville, Tennessee, 37232
Cohen Children's Medical Center
New Hyde Park, New York, 11040
Mt Sinai Hospital
New York, New York, 10029
Morgan Stanley Children's Hospital
New York, New York, 10032
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224
Hasbro Children's Hospital
Providence, Rhode Island, 02903
Primary Children's Medical Center (University of Utah)
Salt Lake City, Utah, 84132
University of California at San Francisco
San Francisco, California, 94143
Golisano Children's Hospital SUNY Upstate Medical University
Syracuse, New York, 13210
Canada3 sites
IWK Health Centre
Halifax, Nova Scotia, B3k6r8
Children's Hospital of Eastern Ontario
Ottawa, Ontario, K1H8L1
Hospital for Sick Children
Toronto, Ontario, M5G1X8
About this study
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.
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 Ulcerative Colitis (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.
Read the detailed description
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 Interleukin 1 (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 (CS) 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 immunomodulators (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.
- Conditions
- Ulcerative Colitis
- Being tested
- Mesalazine, IV Corticosteroid, Oral Corticosteroids, Additional Therapies, Colectomy
- Keywords
- Ulcerative Colitis, mesalamine, corticosteroids, PROTECT
- Medical subject headings
- Colitis, Ulcerative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MesalazineDrug
Also called Pentasa
Mesalazine (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.
IV CorticosteroidDrug
Also called Prednisone
Treatment with IV Corticosteroid
Oral CorticosteroidsDrug
Also called Prednisone
Treatment with oral corticosteroids
Additional TherapiesOther
Anti-TNFα, Calcineurin inhibitor, Immunomodulator
ColectomyProcedure or surgery
Colectomy
| Study group | Role | What they receive |
|---|---|---|
| Mild UC | Experimental | Mild = Initiated on mesalazine, or on oral CS with Pediatric Ulcerative Colitis Activity Index (PUCAI) < 45
Patients can be treated with any of the therapies noted below:
Mesalazine: doses is rounded to the nearest 500mg increment, maximum dose of 75 mg/kg/day Oral corticosteroids:1-1.5 mg/kg/day, rounded up to the nearest 5 mg value
IV corticosteroids:
Additional Therapies:
Calcineurin inhibitor (cyclosporine, tacrolimus) or anti-Tumour Necrosis Factor alpha (TNFα) therapy: These therapies may also be instituted if in the judgment of the attending physician is needed.
Immunomodulator or biologic therapy: thiopurine then dosing of azathioprine:2.5-3 mg/kg/day; 6-MP at 1-1.5 mg/kg/day Colectomy Receives: Drug: Mesalazine; Drug: IV Corticosteroid; Drug: Oral Corticosteroids; Other: Additional Therapies; Procedure: Colectomy |
| Moderate to Severe UC | Experimental | Moderate/Severe = Initiated on IV CS, or oral CS with PUCAI ≥45
Patients can be treated with any of the therapies noted below:
Mesalazine: doses is rounded to the nearest 500mg increment, maximum dose of 75 mg/kg/day Oral corticosteroids:1-1.5 mg/kg/day, rounded up to the nearest 5 mg value
IV corticosteroids:
Additional Therapies:
Calcineurin inhibitor (cyclosporine, tacrolimus) or anti-TNFα therapy: These therapies may also be instituted if in the judgment of the attending physician is needed.
Immunomodulator or biologic therapy: thiopurine then dosing of azathioprine:2.5-3 mg/kg/day; 6-Mercaptopurine (MP) at 1-1.5 mg/kg/day Colectomy Receives: Drug: Mesalazine; Drug: IV Corticosteroid; Drug: Oral Corticosteroids; Other: Additional Therapies; Procedure: Colectomy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Corticosteroid Free Remission (SFR)
Week 52 CS-free remission: Number of participants with a PUCAI < 10 and no corticosteroids (CS) for 28 days without additional therapy or colectomy. Participants in both groups received corticosteroids, biologics, or colectomies, if symptomatic.
The Pediatric Ulcerative Colitis Activity Index (PUCAI) is a non-invasive disease activity index. The index measures include abdominal pain, rectal bleeding, stool consistency, number of stools per 24 hours, nocturnal stools, and activity level. A total score less than 10 indicates remission, Mild disease activity is 10-30, Moderate 35-60, Severe disease activity 65-85.
Measured: 52 weeks
Number of Participants Who Needed Additional Therapy or Colectomy
Number of participants who needed additional therapy or colectomy. Additional therapy included Anti-Tumour Necrosis Factor alpha (TNFα), Calcineurin inhibitor, Immunomodulator
Measured: Within 52 weeks
Secondary outcomes (1)
Number of Participants Receiving a Colectomy
Number of participants who received a colectomy within 52 weeks
Measured: Within 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Feb 2012 (estimated)
- Study start10 Jul 2012
- Primary completion30 Apr 2018
- Study completion30 Apr 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Ulcerative ColitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 431 participants (actual)
Sponsor and investigators
- Lead sponsor
- Connecticut Children's Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jeffrey Hyams, MD, Principal investigator, Connecticut Children's Medical CenterLee Denson, MD, Principal investigator, Children's Hospital Medical Center, CincinnatiSonia Davis, DrPH, Principal investigator, Collaborative Studies Coordinating Center - UNC-CH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01536535
- Sponsor's protocol ID
- U01DK095745-01
- Other IDs
- 1U34DK090804
- Acronym
- PROTECT
- Status last verified
- Sep 2019
- First submitted
- 16 Feb 2012
- Last updated
- 20 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Data will be shared 6 months after the primary publication of the manuscript appears on line.
Publications
Hyams JS, Davis S, Mack DR, Boyle B, Griffiths AM, LeLeiko NS, Sauer CG, Keljo DJ, Markowitz J, Baker SS, Rosh J, Baldassano RN, Patel A, Pfefferkorn M, Otley A, Heyman M, Noe J, Oliva-Hemker M, Rufo P, Strople J, Ziring D, Guthery SL, Sudel B, Benkov K, Wali P, Moulton D, Evans J, Kappelman MD, Marquis A, Sylvester FA, Collins MH, Venkateswaran S, Dubinsky M, Tangpricha V, Spada KL, Britt A, Saul B, Gotman N, Wang J, Serrano J, Kugathasan S, Walters T, Denson LA. Factors associated with early outcomes following standardised therapy in children with ulcerative colitis (PROTECT): a multicentre inception cohort study. Lancet Gastroenterol Hepatol. 2017 Dec;2(12):855-868. doi: 10.1016/S2468-1253(17)30252-2. Epub 2017 Sep 20.
PubMed 28939374Carmody JK, Plevinsky J, Peugh JL, Denson LA, Hyams JS, Lobato D, LeLeiko NS, Hommel KA. Longitudinal non-adherence predicts treatment escalation in paediatric ulcerative colitis. Aliment Pharmacol Ther. 2019 Oct;50(8):911-918. doi: 10.1111/apt.15445. Epub 2019 Aug 2.
PubMed 31373712Hyams JS, Davis Thomas S, Gotman N, Haberman Y, Karns R, Schirmer M, Mo A, Mack DR, Boyle B, Griffiths AM, LeLeiko NS, Sauer CG, Keljo DJ, Markowitz J, Baker SS, Rosh J, Baldassano RN, Patel A, Pfefferkorn M, Otley A, Heyman M, Noe J, Oliva-Hemker M, Rufo PA, Strople J, Ziring D, Guthery SL, Sudel B, Benkov K, Wali P, Moulton D, Evans J, Kappelman MD, Marquis MA, Sylvester FA, Collins MH, Venkateswaran S, Dubinsky M, Tangpricha V, Spada KL, Saul B, Wang J, Serrano J, Hommel K, Marigorta UM, Gibson G, Xavier RJ, Kugathasan S, Walters T, Denson LA. Clinical and biological predictors of response to standardised paediatric colitis therapy (PROTECT): a multicentre inception cohort study. Lancet. 2019 Apr 27;393(10182):1708-1720. doi: 10.1016/S0140-6736(18)32592-3. Epub 2019 Mar 29.
PubMed 30935734
Study at a glance
From the registry record, last updated by the sponsor on 20 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01536535
- Acronym / sponsor ID
- PROTECT / U01DK095745-01
- Conditions
- Ulcerative Colitis
- Keywords
- Ulcerative Colitis, mesalamine, corticosteroids, PROTECT
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 431 participants (actual)
- Lead sponsor
- Connecticut Children's Medical CenterUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 10 Jul 2012 (actual)
- Primary completion
- 30 Apr 2018 (actual)
- Study completion
- 30 Apr 2018 (actual)
- First posted
- 22 Feb 2012 (estimated)
- Results
- Posted 28 Aug 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 Ulcerative Colitis (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.
Detailed description
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 Interleukin 1 (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 (CS) 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 immunomodulators (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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Mild UC | Experimental | Drug: Mesalazine, Drug: IV Corticosteroid, Drug: Oral Corticosteroids, Other: Additional Therapies, Procedure: ColectomyMild = Initiated on mesalazine, or on oral CS with Pediatric Ulcerative Colitis Activity Index (PUCAI) < 45 Patients can be treated with any of the therapies noted below: Mesalazine: doses is rounded to the nearest 500mg increment, maximum dose of 75 mg/kg/day Oral corticosteroids:1-1.5 mg/kg/day, rounded up to the nearest 5 mg value IV corticosteroids: Additional Therapies: Calcineurin inhibitor (cyclosporine, tacrolimus) or anti-Tumour Necrosis Factor alpha (TNFα) therapy: These therapies may also be instituted if in the judgment of the attending physician is needed. Immunomodulator or biologic therapy: thiopurine then dosing of azathioprine:2.5-3 mg/kg/day; 6-MP at 1-1.5 mg/kg/day Colectomy |
| Moderate to Severe UC | Experimental | Drug: Mesalazine, Drug: IV Corticosteroid, Drug: Oral Corticosteroids, Other: Additional Therapies, Procedure: ColectomyModerate/Severe = Initiated on IV CS, or oral CS with PUCAI ≥45 Patients can be treated with any of the therapies noted below: Mesalazine: doses is rounded to the nearest 500mg increment, maximum dose of 75 mg/kg/day Oral corticosteroids:1-1.5 mg/kg/day, rounded up to the nearest 5 mg value IV corticosteroids: Additional Therapies: Calcineurin inhibitor (cyclosporine, tacrolimus) or anti-TNFα therapy: These therapies may also be instituted if in the judgment of the attending physician is needed. Immunomodulator or biologic therapy: thiopurine then dosing of azathioprine:2.5-3 mg/kg/day; 6-Mercaptopurine (MP) at 1-1.5 mg/kg/day Colectomy |
Who may qualify
- Ages
- 4 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (11 listed)
- Age ≥ 4years and ≤17 years at initiation of therapy (achieved 4th birthday, not yet 18th)
- Weight ≥15 kg
- New diagnosis of ulcerative colitis established by standard clinical, endoscopic, and histologic features at the PROTECT study site
- Colitis extending beyond the rectosigmoid (Paris classification E2, E3, or E4)[144]. If a patient is seriously ill and the clinician does not advance the colonoscope beyond the sigmoid colon but the clinical condition of the patient highly suggests more extensive disease then that patient is eligible for study.
- Disease activity by PUCAI of ≥10 at diagnosis
Key exclusion criteria (17 listed)
- Clinical, endoscopic, radiologic, or histologic evidence suggesting Crohn's disease (CD) consistent with Paris and North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) criteria [144, 145]
- A previous diagnosis of inflammatory bowel disease for which treatment was given
- Evidence of any active enteric infection at the time of study entry
- Use of any oral CS for non-gastrointestinal indication within the past 4 weeks (e.g., asthma). Use of inhaled CS does not exclude a patient.
- History of use of IM or anti-TNFα agent for other medical conditions (e.g., juvenile rheumatoid arthritis) within the past 6 months
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MesalazineAlso: PentasaMesalazine (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. | Drug | Mild UC, Moderate to Severe UC |
| IV CorticosteroidAlso: PrednisoneTreatment with IV Corticosteroid | Drug | Mild UC, Moderate to Severe UC |
| Oral CorticosteroidsAlso: PrednisoneTreatment with oral corticosteroids | Drug | Mild UC, Moderate to Severe UC |
| Additional TherapiesAnti-TNFα, Calcineurin inhibitor, Immunomodulator | Other | Mild UC, Moderate to Severe UC |
| ColectomyColectomy | Procedure or surgery | Mild UC, Moderate to Severe UC |
Primary outcome
Number of Participants With Corticosteroid Free Remission (SFR)
Time frame: 52 weeks
Week 52 CS-free remission: Number of participants with a PUCAI < 10 and no corticosteroids (CS) for 28 days without additional therapy or colectomy. Participants in both groups received corticosteroids, biologics, or colectomies, if symptomatic. The Pediatric Ulcerative Colitis Activity Index (PUCAI) is a non-invasive disease activity index. The index measures include abdominal pain, rectal bleeding, stool consistency, number of stools per 24 hours, nocturnal stools, and activity level. A total score less than 10 indicates remission, Mild disease activity is 10-30, Moderate 35-60, Severe disease activity 65-85.
Number of Participants Who Needed Additional Therapy or Colectomy
Time frame: Within 52 weeks
Number of participants who needed additional therapy or colectomy. Additional therapy included Anti-Tumour Necrosis Factor alpha (TNFα), Calcineurin inhibitor, Immunomodulator
1 secondary outcome
Number of Participants Receiving a Colectomy
Time frame: Within 52 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Sep 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 28939374Hyams JS, Davis S, Mack DR, Boyle B, Griffiths AM, LeLeiko NS, Sauer CG, Keljo DJ, Markowitz J, Baker SS, Rosh J, Baldassano RN, Patel A, Pfefferkorn M, Otley A, Heyman M, Noe J, Oliva-Hemker M, Rufo P, Strople J, Ziring D, Guthery SL, Sudel B, Benkov K, Wali P, Moulton D, Evans J, Kappelman MD, Marquis A, Sylvester FA, Collins MH, Venkateswaran S, Dubinsky M, Tangpricha V, Spada KL, Britt A, Saul B, Gotman N, Wang J, Serrano J, Kugathasan S, Walters T, Denson LA. Factors associated with early outcomes following standardised therapy in children with ulcerative colitis (PROTECT): a multicentre inception cohort study. Lancet Gastroenterol Hepatol. 2017 Dec;2(12):855-868. doi: 10.1016/S2468-1253(17)30252-2. Epub 2017 Sep 20.
- Derived from this study: PubMed 31373712Carmody JK, Plevinsky J, Peugh JL, Denson LA, Hyams JS, Lobato D, LeLeiko NS, Hommel KA. Longitudinal non-adherence predicts treatment escalation in paediatric ulcerative colitis. Aliment Pharmacol Ther. 2019 Oct;50(8):911-918. doi: 10.1111/apt.15445. Epub 2019 Aug 2.
- Derived from this study: PubMed 30935734Hyams JS, Davis Thomas S, Gotman N, Haberman Y, Karns R, Schirmer M, Mo A, Mack DR, Boyle B, Griffiths AM, LeLeiko NS, Sauer CG, Keljo DJ, Markowitz J, Baker SS, Rosh J, Baldassano RN, Patel A, Pfefferkorn M, Otley A, Heyman M, Noe J, Oliva-Hemker M, Rufo PA, Strople J, Ziring D, Guthery SL, Sudel B, Benkov K, Wali P, Moulton D, Evans J, Kappelman MD, Marquis MA, Sylvester FA, Collins MH, Venkateswaran S, Dubinsky M, Tangpricha V, Spada KL, Saul B, Wang J, Serrano J, Hommel K, Marigorta UM, Gibson G, Xavier RJ, Kugathasan S, Walters T, Denson LA. Clinical and biological predictors of response to standardised paediatric colitis therapy (PROTECT): a multicentre inception cohort study. Lancet. 2019 Apr 27;393(10182):1708-1720. doi: 10.1016/S0140-6736(18)32592-3. Epub 2019 Mar 29.
- Individual participant dataSharing planned: Yes. Data will be shared 6 months after the primary publication of the manuscript appears on line.
Related trials for Ulcerative Colitis
Active, not recruitingObservational study
A Study to Learn About the Effectiveness of Etrasimod in People With Ulcerative Colitis
Colitis, Ulcerative
RecruitingObservational study
Longitudinal Immunophenotyping of Patients With Inflammatory Bowel Disease
Inflammatory Bowel Disease, Crohn's Disease
RecruitingObservational study
ALPCO Calprotectin CLIA Assay - Measurement of Calprotectin Levels in Human Stool
Inflammatory Bowel Disease (Crohn's Disease and Ulcerative Colitis), Inflammatory Bowel Syndrome
RecruitingPhase 1/2
Study of XmAb942 in Healthy Participants and Participants With Ulcerative Colitis
Ulcerative Colitis (UC)
RecruitingPhase 3
Extension Study of Long-term Safety and Efficacy of Tulisokibart in Participants With Crohn's Disease or Ulcerative Colitis (MK-7240-011)
Crohn Disease, Colitis, Ulcerative
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jeffrey Hyams, MD principal investigator
Connecticut Children's Medical Center
Lee Denson, MD principal investigator
Children's Hospital Medical Center, Cincinnati
Sonia Davis, DrPH principal investigator
Collaborative Studies Coordinating Center - UNC-CH
29 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Mesalazine, IV Corticosteroid and Oral Corticosteroids in people with Ulcerative Colitis, run by Connecticut Children's Medical Center at 29 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 29 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Aug 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Corticosteroid Free Remission (SFR) (time frame: 52 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01536535, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Sep 2019.