The Colitis Once Daily Asacol® study: efficacy and safety of dosing mesalazine in the maintenance of remission of ulcerative colitis

ISRCTN	ISRCTN35600632
DOI	https://doi.org/10.1186/ISRCTN35600632
ClinicalTrials.gov number	NCT00708656
Secondary identifying numbers	HAW0105

Submission date: 23/03/2007
Registration date: 10/05/2007
Last edited: 12/08/2016

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

Not provided at time of registration

Contact information

Dr Barney Hawthorne
Scientific

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

Study information

Study design	Randomised single-blind multi-centre study
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	ISRCTN35600632_PIS_01Jul05.doc
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
Study 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(s)	Leicestershire, Northamptonshire & Rutland Research Ethics Committee 2, 31/01/2006, ref: 05/Q2502/156
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
Pharmaceutical study type(s)
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Asacol®
Primary outcome measure	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 study start date	10/07/2005
Overall study end date	14/07/2011

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	250 (previously 660 prior to 26/06/2009)
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 exclusion criteria	1. Patients with Crohns 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

England
Scotland
United Kingdom
Wales

Study participating centres

Good Hope Hospital

Rectory Road
Sutton Coldfield
B75 7RR
United Kingdom

Rotheram District General Hospital

Morrgate Road
Rotherham
S60 2UD
United Kingdom

Hull Royal Infirmary

Anlaby Road
Hull
HU3 2JZ
United Kingdom

Derby City General Hospital

Uttoxeter Road
Derby
DE22 3NE
United Kingdom

Yeovil District Hospital

Higher Kingston
Yeovil
BA21 4AT
United Kingdom

Russells Hall Hospital

Pensnett Road
Dudley
DY1 2HQ
United Kingdom

Barnsley District General Hospital

Pogmoor Road
Barnsley
S75 2EP
United Kingdom

York District Hospital

Wigginton Road
York
YO31 8HE
United Kingdom

St Luke's Hospital

Little Horton Lane
Bradford
BD5 0NA
United Kingdom

Queen Elizabeth II Hospital

Howlands
Welwyn Garden City
AL7 4HQ
United Kingdom

Royal Berkshire Hospital

London Road
Reading
RG1 5AN
United Kingdom

Royal Cornwall Hospital

2 Penventinnie Lane
Treliske
Truro
TR1 3LQ
United Kingdom

University Hospital Birmingham

Selly Oak Hospital
Birmingham
B29 6JD
United Kingdom

Glan Clwyd Hospital

Rhuddlan Road
Bodelwyddan
Rhyl
LL18 5UJ
United Kingdom

New Cross Hospital

Wednesfield Road
Wolverhampton
WV10 0QP
United Kingdom

Queen Alexandra Hospital

Cosham
Portsmouth
PO6 3LY
United Kingdom

University Hospital of Hartlepool

Holdforth Road
Hartlepool
TS24 9AH
United Kingdom

Glasgow Royal Infirmary

84 Castle Street
Glasgow
G4 0SF
United Kingdom

Darlington Memorial Hospital

Hollyhurst Road
Darlington
DL3 6HX
United Kingdom

Walsgrave General Hospital

Clifford Bridge Road
Walsgrave
Coventry
CV2 2DX

Macclesfield District General Hospital

Victoria Road
Macclesfield
SK10 3BL
United Kingdom

Birmingham Heartlands

Bordesley Green
Birmingham
B9 5ST
United Kingdom

Llandough Hospital

Longcross Street
Cardiff
CF24 0SZ
United Kingdom

University Hospital of Wales

Heath Park
Cardiff
CF14 4XW
United Kingdom

Worcester Royal Hospital

Charles Hastings Way
Worcester
WR5 1DD
United Kingdom

Royal Sussex County Hospital

Eastern Road
Brighton
BN2 5BE
United Kingdom

Worthing Hospital

Lyndhurst Road
Worthing
BN11 2DH
United Kingdom

Bristol Royal Infirmary

Upper Maudlin Street
Bristol
BS2 8HW
United Kingdom

University Hospital of North Tees

Hardwick Road
Hardwick
Stockton-on-Tees
TS19 8PE
United Kingdom

Louth County Hospital

High Holme Road
Louth
LN11 0EU
United Kingdom

The L&D Hospital NHS Foundation Trust

Lowsey Road
Luton
LU4 0DZ
United Kingdom

Sponsor information

Cardiff and Vale NHS Trust (UK)
Hospital/treatment centre

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

Website	http://www.cardiffandvale.wales.nhs.uk/
"ROR"	https://ror.org/0489f6q08

Funders

Funder type

Industry

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

No information available

Results and Publications

Intention to publish date	31/10/2012
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not expected to be made available
Publication and dissemination plan	Planned publication in a peer reviewed journal.
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/10/2012		Yes	No
Participant information sheet		01/07/2005	12/08/2016	No	Yes

Additional files

ISRCTN35600632_PIS_01Jul05.doc: Uploaded 12/08/2016

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.