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| [ Print-friendly version ] |
| Randomised controlled trial of 6-Mercaptopurine (6MP) versus placebo to prevent recurrence of Crohn's disease following surgical resection |
| ISRCTN | ISRCTN89489788 |
| ClinicalTrials.gov identifier | |
| Public title | Randomised controlled trial of 6-Mercaptopurine (6MP) versus placebo to prevent recurrence of Crohn's disease following surgical resection |
| Scientific title | |
| Acronym | TOPPIC (Trial Of Prevention of Post-operative Crohn's disease) |
| Serial number at source | G0600329 |
| Study hypothesis |
Therapy with 6 MP prevents or delays post-operative recurrence of Crohn's disease.
A lay summary is available on http://www.clinicaltrials.ed.ac.uk/trials/toppic/toppic_lay_summary.pdf As of 15/03/2011 the anticipated end date for this trial has been updated from 30/09/2013 to 31/03/2015 |
| Lay summary | |
| Ethics approval | Scotland A Research Ethics Committee, NHS Scotland. Date of approval: 14/08/2007 (REC Ref No: 07/MRE00/74) |
| Study design | Multi-centre double blind randomised placebo-controlled trial |
| Countries of recruitment | United Kingdom |
| Disease/condition/study domain | Crohn's disease |
| Participants - inclusion criteria |
Current inclusion criteria as of 15/03/2011:
1. At least 16 years of age in Scotland and 18 years of age in England and Wales. 2. Established diagnosis of Crohn¡¯s disease confirmed at recent resection. 3. Ileocolonic or small bowel resection within 3 months before screening. 4. No more than 100 cm of fixed small bowel resected in total. Previous ileocolonic resection is acceptable. 5. Able to start oral nutrition within the first 2 postoperative weeks. 6. Normal or heterozygous TPMT (activity present or reduced consistent with carrier status). 7. Able to provide written informed consent prior to screening and to comply with the requirements of the study protocol. 8. Off antibiotics 2 weeks prior to randomisation. Previous inclusion criteria: 1. Male or female, at least 16 years of age in Scotland and 18 years of age in England and Wales 2. Established diagnosis of Crohn’s disease 3. Ileocolonic resection within 3 months 4. Able to start oral nutrition and medication within the first 2 postoperative weeks 5. Normal or heterozygous Thio Purine Methyl-Transferase (TPMT) genotype 6. No more than 100 cms of fixed small bowel resected in total. Previous ileocolonic resection is acceptable 7. Able to provide written informed consent prior to screening and to comply with the requirements of the study protocol |
| Participants - exclusion criteria |
Current exclusion criteria as of 15/03/2011:
1. Pregnancy at baseline or breast feeding. 2. A known hypersensitivity or intolerance to 6MP 3. Pancreatitis associated with azathioprine. 4. Receiving an experimental treatment for Crohn¡¯s disease in the 4 weeks prior to study entry. 5. Known to require further surgery at study entry i.e. for the removal of an abscess developing from the primary surgery. 6. Strictureplasty procedure alone (Please note that strictureplasty and resection procedure together will not be considered an exclusion.) 7. Presence of stoma. 8. Significant haematological, renal or hepatic dysfunction or clinically important lung disease (i.e. liver function tests (except GGT) >x2 upper limit of normal, Haemoglobin ¡Ü10, total white blood cell count <3.5, Neutrophils <1.5, Platelets <100x106/l). 9. Systemic infection including hepatitis B, hepatitis C, HIV and active TB. 10. A diagnosis of indeterminate colitis or ulcerative colitis. 11. A history of illicit drug or alcohol abuse in the 1 year prior to study entry. 12. Active or untreated malignancy (excluding basal cell carcinoma and insitu tumours). (Patients who have had successful treatment for malignancy and have been in remission for more than 5 years may be considered for inclusion only after detailed discussion with, and written approval, from the patient's medical oncologist.) 13. Presence of a medical or psychiatric condition, disease or laboratory abnormality that in the opinion of the PI may place the subject at unacceptable risk during the study. 14. Homozygous deficient for TPMT (absent activity) 15. Evidence of untreated post-operative infection e.g. clostridium difficile, urinary tract infection or chest infection. If these have been appropriately treated in the opinion of the PI, and inclusion criteria 8 is met, this will not be considered an exclusion. 16. Taking any medication for Crohn¡¯s disease. Previous exclusion criteria: 1. Pregnancy or breast feeding 2. Hypersensitivity or intolerance to 6MP or pancreatitis associated with azathioprine 3. Receiving an experimental treatment for Crohn’s disease in the 4 weeks prior to study entry 4. Known to require further surgery at study entry 5. Presence of stoma 6. Significant renal or hepatic dysfunction, clinically important lung disease 7. Systemic infection including hepatitis C, HIV and active tuberculosis (TB) 8. A diagnosis of indeterminate colitis or ulcerative colitis 9. A history of illicit drug or alcohol abuse in the 1 year prior to study entry 10. History of cancer - excluding basal cell carcinoma treated more than 5 years previously and in-situ tumours 11. Presence of a medical or psychiatric condition, disease or laboratory abnormality that in the opinion of the PI may place the subject at unacceptable risk during the study 12. Homozygous deficient for TPMT 13. Initiation of the following drugs during the study is not allowed: corticosteroids (it is expected that patients may be on corticosteroids at entry. Doses will be tapered according to local protocols), anti-tumour necrosis factor, azathioprine, methotrexate, antibiotics (for a duration of >10 days), non steroidal anti-inflammatory drugs |
| Anticipated start date | 01/10/2007 |
| Anticipated end date | 31/05/2015 |
| Status of trial | Ongoing |
| Patient information material | |
| Target number of participants | 234, recruited over 3 years. |
| Interventions | Patients randomised to treatment with 6MP or matching placebo. 6MP will be given at a dose of 1 mg per kg body weight per day, rounded to the nearest 25 mg, for 3 years or until study drug is permanently discontinued. Safety monitoring of 6MP will be performed continuously throughout the trial, involving full blood count and liver function tests at appropriate intervals |
| Primary outcome measure(s) | Post-operative recurrence of Crohn’s disease requiring anti-inflammatory rescue therapy and time of recurrence. |
| Secondary outcome measure(s) |
1. The need for a second operation to remove recurrent Crohn’s disease from the anastomotic site
2. Changes in quality of life scores (assessed at 4 weeks [baseline / randomisation], 17 weeks, 1 year, 2 and 3 years using Inflammatory Bowel Disease Questionnaire [IBDQ], Medical Outcome Survey Short Form 36 [SF-36] and EQ-5D) 3. Endoscopic recurrence of Crohn’s disease (assessed at 1 year and 3 years) 4. Relation of faecal calprotectin to time of disease recurrence 5. Relation of drug metabolite levels to time of disease recurrence 6. Exploratory analyses of clinical, genetic and serological markers for predicting disease recurrence |
| Sources of funding | Medical Research Council (UK) (Grant No: G0600329) |
| Trial website | http://www.clinicaltrials.ed.ac.uk/trials/toppic/default.asp |
| Publications | |
| Contact name | Prof Jack Satsangi |
| Address |
Professor of Gastroenterology
Department of Gastrointestinal Medicine Western General Hospital Crewe Road South |
| City/town | Edinburgh |
| Zip/Postcode | EH4 2XU |
| Country | United Kingdom |
| Sponsor | University of Edinburgh, Lothian Health Board, University Hospitals Division (UK) |
| Address |
Marise Bucukoglu
Clinical Trials & Research Governance Manager College of Medicine & Veterinary Medicine The Queen's Medical Research Institute The University of Edinburgh |
| City/town | Edinburgh |
| Zip/Postcode | EH16 4TJ |
| Country | United Kingdom |
| Date applied | 22/02/2007 |
| Last edited | 15/03/2011 |
| Date ISRCTN assigned | 15/06/2007 |
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