Condition category
Digestive System
Date applied
22/02/2007
Date assigned
15/06/2007
Last edited
17/12/2015
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Contact information

Type

Scientific

Primary contact

Prof Jack Satsangi

ORCID ID

Contact details

Professor of Gastroenterology
Department of Gastrointestinal Medicine
Western General Hospital
Crewe Road South
Edinburgh
EH4 2XU
United Kingdom

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, REC Ref No: 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

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

Other

Phase

Not Applicable

Drug names

Primary outcome measures

Post-operative recurrence of Crohn’s disease requiring anti-inflammatory rescue therapy and time of recurrence.

Secondary outcome measures

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

Overall trial start date

01/10/2007

Overall trial end date

30/09/2015

Reason abandoned

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 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

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 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

Recruitment start date

01/10/2007

Recruitment end date

31/03/2015

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Professor of Gastroenterology
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

private sector organisation

Funding Body Subtype

other non-profit

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

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

17/12/2015: The overall trial end date has been extended from 31/03/2015 to 30/09/2015.