Condition category
Digestive System
Date applied
23/03/2007
Date assigned
10/05/2007
Last edited
12/08/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Barney Hawthorne

ORCID ID

Contact details

C7
University Hospital of Wales
Heath Park
Cardiff
CF14 4XW
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

NCT00708656

Protocol/serial number

HAW0105

Study information

Scientific title

A randomised, multicentre, parallel group single-blind study to assess the efficacy and safety of dosing mesalazine 800 mg tablets (Asacol®) at 2.4 g once daily versus divided doses three times daily for 12 months in the maintenance of remission of ulcerative colitis

Acronym

CODA

Study hypothesis

Does Asacol® 2.4 g taken daily as a single morning dose prevent relapses of ulcerative colitis as effectively and safely as 800 mg taken three times a day, over a one year period?

Ethics approval

Leicestershire, Northamptonshire & Rutland Research Ethics Committee 2, 31/01/2006, ref: 05/Q2502/156

Study design

Randomised single-blind multi-centre study

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

See additional files

Condition

Ulcerative colitis

Intervention

This is a randomised, single-blind, multicentre study in patients with ulcerative colitis who have been in remission for more than four weeks, but no longer than two years, and who are already taking 5-ASA therapy. It will involve approximately 40 to 50 study sites in the UK.

Asacol® 2.4 g daily, taken orally as a single morning dose versu 800 mg taken three times a day, over one-year period.

Intervention type

Drug

Phase

Not Applicable

Drug names

Asacol®

Primary outcome measures

Proportion in each treatment group who have relapsed by one year, based on an intention to treat. All available follow-up data will be utilised. A per protocol analysis will also be performed restricted to those complying fully with the protocol (who complete the study regardless of treatment outcome, meet inclusion and exclusion criteria, and who take study medication as prescribed, with compliance more than 75%).

Non-inferiority will be concluded if the upper limit of the 95% confidence interval (one sided) for the difference in the proportion of patients relapsing at one year between intervention and control is less than 10%, based on an intention to treat analysis.

Secondary analyses with the primary outcome will repeat the primary analysis, but on a per protocol basis. Where non-inferiority has been shown, a superiority analysis will be conducted. Additional exploratory analysis will assess whether other factors such as time since last relapse prior to study entry, concomitant therapies, extent of disease, disease duration, smoking status, age at diagnosis, and baseline measures act as effect modifiers using logistic regression.

Secondary outcome measures

Secondary analysis will be conducted on both an intention to treat and per protocol basis. The two groups will be compared in terms of the proportion of patients experiencing adverse reactions in each group. It is estimated that this rate will be 2 - 4%. This low rate is likely because all patients entering the study will have already been using mesalazine-containing products. Non-inferiority in terms of safety will be concluded if the limit of 95% one-sided confidence interval for the difference in rate of adverse reactions is less than 4% (with 80% power, assuming an event rate of 4%) . Time until relapse will be compared between the two groups using Kaplan Meier curves.

Mayo scores will be analysed by comparing changes at relapse or 12 months, in comparison to baseline. Individual components of the Mayo score, particularly sigmoidoscopy score, but also rectal bleeding and diarrhoea will be analysed independently.

For each participant, tablet counts will be carried out to estimate a daily dosage in order to check his/her compliance throughout the period of study. The mean daily dosage will be compared between the two groups using a t-test.

Overall trial start date

10/07/2005

Overall trial end date

14/07/2011

Reason abandoned

Eligibility

Participant inclusion criteria

1. Male and female patients aged over 18 with ulcerative colitis confirmed by histology who are in remission (no symptoms of active disease, and modified Baron sigmoidoscopic score of 0 or 1)
2. If female, must be (as documented in patient notes) one of the following:
2.1. Post-menopausal (at least 1 year without spontaneous menses)
2.2. Surgically sterile (tubal ligation or hysterectomy at least 6 months prior to enrolment)
2.3. Using acceptable contraception (e.g. oral, intramuscular, or implanted hormonal contraception) at least 3 months prior to enrolment
2.4. Have a sexual partner with non-reversed vasectomy (with confirmed azoospermia)
2.5. Using 1 barrier method (e.g. condom, diaphragm, spermicide, or intra-uterine device)
3. Patients whose ulcerative colitis has been in clinical remission for 4 weeks or longer, and who have had a symptomatic relapse within the past two years
4. Patients taking mesalazine, sulfasalazine or other drug containing 5-aminosalicylic acid (5-ASA) for 4 weeks or longer
5. Patients capable of giving written informed consent

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

250 (previously 660 prior to 26/06/2009)

Participant exclusion criteria

1. Patients with Crohn’s disease
2. Patients with symptoms of active colitis
3. Modified Baron sigmoidoscopy score of 2 or 3
4. Patients who have used oral, enema, intravenous or suppository preparations of corticosteroids, oral or intravenous ciclosporin, mesalazine enemas or suppositories within the past four weeks
5. Patients taking azathioprine or 6-mercaptopurine who have altered the dose or started treatment within the past three months (these drugs are permitted in stable dose during the study)
6. Patients with intolerance to Asacol® 400 mg or mesalazine
7. Women who are pregnant or lactating
8. Patients with known human immunodeficiency virus (HIV) infection
9. Patients with hepatic disease
10. Patients with renal impairment (creatinine above local reference range), or with positive urine dipstick test to blood or protein
11. Other serious medical or psychiatric illness that in the opinion of the investigator would possibly comprise the study
12. Patients with problem alcohol excess or drug abuse

Recruitment start date

16/10/2006

Recruitment end date

30/06/2009

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Good Hope Hospital
Rectory Road
Sutton Coldfield
B75 7RR
United Kingdom

Trial participating centre

Rotheram District General Hospital
Morrgate Road
Rotherham
S60 2UD
United Kingdom

Trial participating centre

Hull Royal Infirmary
Anlaby Road
Hull
HU3 2JZ
United Kingdom

Trial participating centre

Derby City General Hospital
Uttoxeter Road
Derby
DE22 3NE
United Kingdom

Trial participating centre

Yeovil District Hospital
Higher Kingston
Yeovil
BA21 4AT
United Kingdom

Trial participating centre

Russells Hall Hospital
Pensnett Road
Dudley
DY1 2HQ
United Kingdom

Trial participating centre

Barnsley District General Hospital
Pogmoor Road
Barnsley
S75 2EP
United Kingdom

Trial participating centre

York District Hospital
Wigginton Road
York
YO31 8HE
United Kingdom

Trial participating centre

St Luke's Hospital
Little Horton Lane
Bradford
BD5 0NA
United Kingdom

Trial participating centre

Queen Elizabeth II Hospital
Howlands
Welwyn Garden City
AL7 4HQ
United Kingdom

Trial participating centre

Royal Berkshire Hospital
London Road
Reading
RG1 5AN
United Kingdom

Trial participating centre

Royal Cornwall Hospital
2 Penventinnie Lane Treliske
Truro
TR1 3LQ
United Kingdom

Trial participating centre

University Hospital Birmingham
Selly Oak Hospital
Birmingham
B29 6JD
United Kingdom

Trial participating centre

Glan Clwyd Hospital
Rhuddlan Road Bodelwyddan
Rhyl
LL18 5UJ
United Kingdom

Trial participating centre

New Cross Hospital
Wednesfield Road
Wolverhampton
WV10 0QP
United Kingdom

Trial participating centre

Queen Alexandra Hospital
Cosham
Portsmouth
PO6 3LY
United Kingdom

Trial participating centre

University Hospital of Hartlepool
Holdforth Road
Hartlepool
TS24 9AH
United Kingdom

Trial participating centre

Glasgow Royal Infirmary
84 Castle Street
Glasgow
G4 0SF
United Kingdom

Trial participating centre

Darlington Memorial Hospital
Hollyhurst Road
Darlington
DL3 6HX
United Kingdom

Trial participating centre

Walsgrave General Hospital
Clifford Bridge Road Walsgrave
Coventry
CV2 2DX

Trial participating centre

Macclesfield District General Hospital
Victoria Road
Macclesfield
SK10 3BL
United Kingdom

Trial participating centre

Birmingham Heartlands
Bordesley Green
Birmingham
B9 5ST
United Kingdom

Trial participating centre

Llandough Hospital
Longcross Street
Cardiff
CF24 0SZ
United Kingdom

Trial participating centre

University Hospital of Wales
Heath Park
Cardiff
CF14 4XW
United Kingdom

Trial participating centre

Worcester Royal Hospital
Charles Hastings Way
Worcester
WR5 1DD
United Kingdom

Trial participating centre

Royal Sussex County Hospital
Eastern Road
Brighton
BN2 5BE
United Kingdom

Trial participating centre

Worthing Hospital
Lyndhurst Road
Worthing
BN11 2DH
United Kingdom

Trial participating centre

Bristol Royal Infirmary
Upper Maudlin Street
Bristol
BS2 8HW
United Kingdom

Trial participating centre

University Hospital of North Tees
Hardwick Road Hardwick
Stockton-on-Tees
TS19 8PE
United Kingdom

Trial participating centre

Louth County Hospital
High Holme Road
Louth
LN11 0EU
United Kingdom

Trial participating centre

The L&D Hospital NHS Foundation Trust
Lowsey Road
Luton
LU4 0DZ
United Kingdom

Sponsor information

Organisation

Cardiff and Vale NHS Trust (UK)

Sponsor details

Research and Development Department
Ground floor
Radnor House
University Hospital of Wales
Heath Park
Cardiff
CF14 4XW
United Kingdom

Sponsor type

Government

Website

http://www.cardiffandvale.wales.nhs.uk/

Funders

Funder type

Industry

Funder name

Procter and Gamble Pharmaceuticals (USA) - provided a donation, managed by the study Sponsor (Cardiff and Vale NHS Trust) (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Planned publication in a peer reviewed journal.

Intention to publish date

31/10/2012

Participant level data

Not expected to be available

Results - basic reporting

Publication summary

2012 results in http://www.ncbi.nlm.nih.gov/pubmed/22081522

Publication citations

Additional files

Editorial Notes

12/08/2016: The overall trial dates have been updated from 01/10/2006 - 30/06/2010 to 10/07/2005 - 14/07/2011 and the recruitment dates have been updated from 01/10/2006 - 30/06/2010 to 16/10/2006 - 31/06/2009. In addition, the participant information sheet has been uploaded and the trial participating centres have been added. Publication reference added. 15/07/2016: No publications found, verifying study status with principal investigator. 06/07/2009: Recruitment has now been completed as of 30th June 2009. The last patient will complete the trial on the 30th June 2010. 26/06/2009: This record has been updated to include an update to the anticipated end date of this trial; the initial end date at the time of registration was 31/12/2007. Please note that at this time the target number of participants was also amended.