Randomised controlled trial of 6-Mercaptopurine (6MP) versus placebo to prevent recurrence of Crohn's disease following surgical resectio

Not Applicable

Completed

Conditions: Crohn's disease
Digestive System

Registration Number: ISRCTN89489788

Lead Sponsor: niversity of Edinburgh, Lothian Health Board, University Hospitals Division (UK)

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: All

Target Recruitment: 234

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 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

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 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

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Post-operative recurrence of Crohn?s disease requiring anti-inflammatory rescue therapy and time of recurrence

Secondary Outcome Measures

Name	Time	Method
1. The need for a second operation to remove recurrent Crohn?s disease from the anastomotic site<br>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)<br>3. Endoscopic recurrence of Crohn?s disease (assessed at 1 year and 3 years) <br>4. Relation of faecal calprotectin to time of disease recurrence<br>5. Relation of drug metabolite levels to time of disease recurrence<br>6. Exploratory analyses of clinical, genetic and serological markers for predicting disease recurrence