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| [ Print-friendly version ] |
| The Colitis Once Daily Asacol® study: efficacy and safety of dosing mesalazine in the maintenance of remission of ulcerative colitis |
| ISRCTN | ISRCTN35600632 |
| ClinicalTrials.gov identifier | NCT00708656 |
| Public title | The Colitis Once Daily Asacol® study: efficacy and safety of dosing mesalazine in the maintenance of remission of ulcerative colitis |
| 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 |
| Serial number at source | HAW0105 |
| 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?
As of 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. |
| Ethics approval | Leicestershire, Northamptonshire & Rutland Research Ethics Committee 2 approved on the 31st January 2006 (ref: 05/Q2502/156). |
| Study design | Randomised single-blind multi-centre study |
| Countries of recruitment | United Kingdom |
| Disease/condition/study domain | Ulcerative colitis |
| Participants - 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 |
| Participants - 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 |
| Anticipated start date | 01/10/2006 |
| Anticipated end date | 30/06/2010 |
| Status of trial | Completed |
| Patient information material | Not available in web format, please use the contact details below to request a patient information sheet |
| Target number of participants | 250 (previously 660 prior to 26/06/2009) |
| Interventions |
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. Added 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. |
| Primary outcome measure(s) |
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 measure(s) |
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. |
| Sources of funding | Procter and Gamble Pharmaceuticals (USA) - provided a donation, managed by the study Sponsor (Cardiff and Vale NHS Trust) (UK) |
| Trial website | |
| Publications | |
| Contact name | Dr Barney Hawthorne |
| Address |
C7
University Hospital of Wales Heath Park |
| City/town | Cardiff |
| Zip/Postcode | CF14 4XW |
| Country | United Kingdom |
| Sponsor | Cardiff and Vale NHS Trust (UK) |
| Address |
Research and Development Department
Ground floor, Radnor House University Hospital of Wales Heath Park |
| City/town | Cardiff |
| Zip/Postcode | CF14 4XW |
| Country | United Kingdom |
| Sponsor website: | http://www.cardiffandvale.wales.nhs.uk/ |
| Date applied | 23/03/2007 |
| Last edited | 06/07/2009 |
| Date ISRCTN assigned | 10/05/2007 |
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