Predicting Response to Standardized Pediatric Colitis Therapy
PROTECT
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.
2 other identifiers
interventional
431
2 countries
29
Brief 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). 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_4
Started Jul 2012
Longer than P75 for phase_4
29 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 16, 2012
CompletedFirst Posted
Study publicly available on registry
February 22, 2012
CompletedStudy Start
First participant enrolled
July 10, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 30, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
April 30, 2018
CompletedResults Posted
Study results publicly available
August 28, 2019
CompletedSeptember 20, 2019
September 1, 2019
5.8 years
February 16, 2012
August 6, 2019
September 4, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
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.
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
Within 52 weeks
Secondary Outcomes (1)
Number of Participants Receiving a Colectomy
Within 52 weeks
Study Arms (2)
Mild UC
EXPERIMENTALMild = 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
EXPERIMENTALModerate/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
Interventions
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.
Treatment with IV Corticosteroid
Treatment with oral corticosteroids
Anti-TNFα, Calcineurin inhibitor, Immunomodulator
Eligibility Criteria
You may qualify if:
- 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
- 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.
You may not qualify if:
- 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
- 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
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (29)
UCLA Medical Center
Los Angeles, California, 90095, United States
University of California at San Francisco
San Francisco, California, 94143, United States
Connecticut Children's Medical Center
Hartford, Connecticut, 06106, United States
Nemours Children's Clinic
Jacksonville, Florida, 32207, United States
Emory Children's Center
Atlanta, Georgia, 30322, United States
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611-2605, United States
Riley Children's Hospital
Indianapolis, Indiana, 46202, United States
John Hopkins Children's Hospital
Baltimore, Maryland, 21287, United States
Children's Hospital of Boston
Boston, Massachusetts, 02115, United States
University of Minnesota Medical Center
Minneapolis, Minnesota, 55454, United States
Goryeb Children's Hospital / Atlantic Health
Morristown, New Jersey, 07962, United States
Women and Children's Hospital of Buffalo
Buffalo, New York, 14222, United States
Cohen Children's Medical Center
New Hyde Park, New York, 11040, United States
Mt Sinai Hospital
New York, New York, 10029, United States
Morgan Stanley Children's Hospital
New York, New York, 10032, United States
Golisano Children's Hospital SUNY Upstate Medical University
Syracuse, New York, 13210, United States
University of North Carolina at Chapel HIll
Chapel Hill, North Carolina, 27599, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229, United States
Nationwide Children's Hospital
Columbus, Ohio, 43205, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224, United States
Hasbro Children's Hospital
Providence, Rhode Island, 02903, United States
Monroe Carell Jr. Children's Hospital at Vanderbilt
Nashville, Tennessee, 37232, United States
UT Southwestern
Dallas, Texas, 75235, United States
Primary Children's Medical Center (University of Utah)
Salt Lake City, Utah, 84132, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226, United States
IWK Health Centre
Halifax, Nova Scotia, B3k6r8, Canada
Children's Hospital of Eastern Ontario
Ottawa, Ontario, K1H8L1, Canada
Hospital for Sick Children
Toronto, Ontario, M5G1X8, Canada
Related Publications (3)
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.
PMID: 28939374RESULTCarmody 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.
PMID: 31373712DERIVEDHyams 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.
PMID: 30935734DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Jeffrey Hyams
- Organization
- Connecticut Childrens
Study Officials
- 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
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 16, 2012
First Posted
February 22, 2012
Study Start
July 10, 2012
Primary Completion
April 30, 2018
Study Completion
April 30, 2018
Last Updated
September 20, 2019
Results First Posted
August 28, 2019
Record last verified: 2019-09
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE
- Time Frame
- Data will be shared 6 months after the primary publication of the manuscript appears on line.
- Access Criteria
- NIH repository list serve to be determined
Data will be shared 6 months after the primary publication of the manuscript appears on line.