Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
G0600329
Study information
Scientific title
Randomised controlled trial of 6-Mercaptopurine (6MP) versus placebo to prevent recurrence of Crohn's disease following surgical resection
Acronym
TOPPIC (Trial Of Prevention of Post-operative Crohn's disease)
Study hypothesis
Therapy with 6 MP prevents or delays post-operative recurrence of Crohn's disease.
Ethics approval
Scotland A Research Ethics Committee, NHS Scotland, 14/08/2007, ref: 07/MRE00/74
Study design
Multi-centre double-blind randomised placebo-controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Condition
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
Phase
Not Applicable
Drug names
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 trial start date
01/10/2007
Overall trial end date
30/09/2015
Reason abandoned (if study stopped)
Eligibility
Participant 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
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
234, recruited over 3 years.
Participant 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
Recruitment start date
01/10/2007
Recruitment end date
31/03/2015
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Western General Hospital
Edinburgh
EH4 2XU
United Kingdom
Sponsor information
Organisation
University of Edinburgh, Lothian Health Board, University Hospitals Division (UK)
Sponsor details
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
United Kingdom
Sponsor type
University/education
Website
Funders
Funder type
Government
Funder name
Medical Research Council (UK) (Grant No: G0600329)
Alternative name(s)
MRC
Funding Body Type
government organisation
Funding Body Subtype
Federal/National Government
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2016 results in: https://www.ncbi.nlm.nih.gov/pubmed/28404197