Randomised controlled trial of 6-Mercaptopurine (6MP) versus placebo to prevent recurrence of Crohn's disease following surgical resection
| ISRCTN | ISRCTN89489788 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN89489788 |
| Secondary identifying numbers | G0600329 |
- Submission date
- 22/02/2007
- Registration date
- 15/06/2007
- Last edited
- 18/04/2017
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Digestive System
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Contact information
Prof Jack Satsangi
Scientific
Scientific
Professor of Gastroenterology
Department of Gastrointestinal Medicine
Western General Hospital
Crewe Road South
Edinburgh
EH4 2XU
United Kingdom
Study information
| Study design | Multi-centre double-blind randomised placebo-controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | Randomised controlled trial of 6-Mercaptopurine (6MP) versus placebo to prevent recurrence of Crohn's disease following surgical resection |
| Study acronym | TOPPIC (Trial Of Prevention of Post-operative Crohn's disease) |
| Study objectives | Therapy with 6 MP prevents or delays post-operative recurrence of Crohn's disease. |
| Ethics approval(s) | Scotland A Research Ethics Committee, NHS Scotland, 14/08/2007, ref: 07/MRE00/74 |
| Health condition(s) or problem(s) studied | Crohn's disease |
| Intervention | 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 |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Mercaptopurine |
| Primary outcome measure | Post-operative recurrence of Crohns disease requiring anti-inflammatory rescue therapy and time of recurrence |
| Secondary outcome measures | 1. The need for a second operation to remove recurrent Crohns 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 Crohns 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 |
| Overall study start date | 01/10/2007 |
| Completion date | 30/09/2015 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 234, recruited over 3 years. |
| Key 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 Crohns 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 cm 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 |
| Key exclusion criteria | Current exclusion criteria as of 15/03/2011: 1. Pregnancy at baseline or breastfeeding 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 in situ 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 breastfeeding 2. Hypersensitivity or intolerance to 6MP or pancreatitis associated with azathioprine 3. Receiving an experimental treatment for Crohns 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 |
| Date of first enrolment | 01/10/2007 |
| Date of final enrolment | 31/03/2015 |
Locations
Countries of recruitment
- Scotland
- United Kingdom
Study participating centre
Western General Hospital
Edinburgh
EH4 2XU
United Kingdom
EH4 2XU
United Kingdom
Sponsor information
University of Edinburgh, Lothian Health Board, University Hospitals Division (UK)
University/education
University/education
c/o Marise Bucukoglu
Clinical Trials & Research Governance Manager
College of Medicine & Veterinary Medicine
The Queen's Medical Research Institute
The University of Edinburgh
Edinburgh
EH16 4TJ
Scotland
United Kingdom
"ROR" |
https://ror.org/01nrxwf90 |
|---|
Funders
Funder type
Government
Medical Research Council (UK) (Grant No: G0600329)
Government organisation / National government
Government organisation / National government
- Alternative name(s)
- Medical Research Council (United Kingdom), UK Medical Research Council, MRC
- Location
- United Kingdom
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/12/2016 | Yes | No |
Editorial Notes
18/04/2017: Publication reference added.
17/12/2015: The overall trial end date has been extended from 31/03/2015 to 30/09/2015.
