Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT03487900 |
| Other study ID # |
GETAID 2017-002 |
| Secondary ID |
2017-003345-15 |
| Status |
Active, not recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
March 13, 2018 |
| Est. completion date |
December 31, 2023 |
Study information
| Verified date |
August 2022 |
| Source |
Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The CREDO 2 study follows CREDO 1 study, which aims to construct an objective evaluation of
endoscopic remission in Crohn's Disease (CD). In addition to reproducibility and validation,
the predictive value of this remission evaluation needs to be tested in different settings to
valorise its usefulness in clinical practice and in clinical trials.
CREDO 2 aims to investigate whether the evaluation of endoscopic remission, as defined in
CREDO 1, in patients in clinical remission is predictive of sustained clinical remission at 2
years.
The design of CREDO2 is a multicentre longitudinal prospective cohort study. The screening
period to include a patient is two weeks. Patients will be followed up to week 104.
Description:
The CREDO 2 study follows CREDO 1 study, which aims to construct an objective evaluation of
endoscopic remission in Crohn's Disease (CD). In addition to reproducibility and validation,
the predictive value of this remission evaluation needs to be tested in different settings to
valorise its usefulness in clinical practice and in clinical trials.
CREDO 2 aims to investigate whether the evaluation of endoscopic remission, as defined in
CREDO 1, in patients in clinical remission is predictive of sustained clinical remission at 2
years. The design of CREDO2 is a multicentre longitudinal prospective cohort study. The
screening period to include a patient is two weeks. Patients will be followed up to week 104.
The primary endpoint is sustained clinical remission at week 104. The primary secondary
endpoints are sustained clinical remission at weeks 26 and 52. The sustained clinical
remission at 2 years is defined by the absence of relapse and complication of the disease.
Relapse is defined as Crohn's Disease Activity Index (CDAI) > 220 or between 150 and 220 for
2 consecutive weeks with an increase of at least 70 points relative to the baseline CDAI,
associated with an objective marker of inflammation: C-reactive protein (CRP) ≥5 mg/l and /
or faecal calprotectin ≥250 μg/g. CD complication is defined by an intestinal resection
surgery for CD, stricturoplasty, endoscopic dilatation, hospitalisation for intestinal
strictures, abscess and / or fistula (including anoperineal disease) and/or therapeutic
escalation. Therapeutic escalation is defined as an increase in the dosage of the treatment,
shortening of the treatment interval, addition of a new treatment for CD (including
corticosteroids, immunosuppressants, biologics, Janus kinase (JAK) inhibitors or any
experimental treatment). The number of patients to be included is 320 when using a two-sided
test with a type 1 error of 5% to detect with a power of 80% an association between a
predictor and week 104 sustained remission failure, corresponding to a variation in
proportions of patients who failed from 40% in the high-risk group to 20% in the low-risk
group, and assuming a 12% loss due to treatment discontinuation or patient withdrawal.
Patients will be recruited via two cohorts. First, patients included in CREDO 1 could be
included in CREDO 2 if they agree and meet the criteria of non-exclusion. Assuming that 2/3
of the 15 patients included in each of the 16 centres involved in CREDO 1 could be included
in CREDO 2, 160 patients will be included from CREDO 1. An additional cohort of 10 patients
per centre will be included in CREDO 2 by the same local investigator within each centre
using the same methods as for CREDO 1 cohort, except that recruitment criteria will be those
of CREDO 2, to provide 160 additional patients to reach the targeted cohort size for CREDO 2.
Recruitment will therefore be performed in 16 centres and each local investigator will have
to register 20 videos, including those selected from CREDO 1, stratified by endoscopic
remission status according to his/her global judgment: complete remission; almost complete
remission; neither complete nor almost complete remission. The main inclusion criteria are
adult patients, with established CD with ileal and / or colonic involvement, without
significant clinical activity for more than 3 consecutive months with, at baseline, CDAI <150
and CRP <5 mg / l and faecal calprotectin <250 μg / g, stable maintenance treatment for more
than 3 months, an ileocolonoscopy planned for CD and the decision to maintain or decrease the
treatment (but not increase) after the colonoscopy. All maintenance treatments are authorized
/ immunosuppressive (azathioprine, 6-mercaptopurine, methotrexate), biologic (infliximab,
adalimumab, certolizumab, golimumab, ustekinumab, vedolizumab) and JAK inhibitors.The main
exclusion criteria are an incomplete record of the ileocolonoscopy or more than three
resected ileocolonic segments (not counting ileocecal valve), taking NSAIDs in the two weeks
prior to endoscopy, anoperineal MC without luminal involvement, suspicion of intestinal
infection within 4 weeks prior to baseline endoscopic assessment. The expected period of
recruitment is 12 months from the first patient included in the study and 20 patients will be
included in each of the 16 centres in Belgium and France. At inclusion, demographic,
phenotypic, medical history and treatment data will be collected and ileocolonoscopy will be
performed and recorded by the local investigator using pre-specified standards, provided
sufficient quality. Biological (albumin, haemoglobin, platelets, CRP and faecal calprotectin)
assessments will be carried out at the inclusion and at each follow-up visit (week 26, 52 104
and unplanned). The clinical activity will be evaluated through CDAI. Within each centre, the
local investigator, as local reader, will read the 20 ileocolonoscopy videos of the centre.
In addition, each video will be read by central readers, selected among 12 central readers in
four groups of 3 central readers. Each video will be read by 2 central readers and by a third
one in case of disagreement between the first two. Each central reader will read a little
more than 54 videos due to these disagreements. All these readers, local and central, will
have undergone the training session validated by an examination on the evaluation of
endoscopic remission. In a separate delayed session, the central readers will evaluate
components of usual endoscopic severity indices. Agreement between data provided by local
readers and central readers will be assessed through Kappa and intraclass correlation
coefficient estimates. If agreement is satisfactory, endoscopic data provided by local
readers will be used to investigate the association between baseline endoscopic evaluation
and sustained clinical remission at week 104 using the logistic regression method, ROC
curves, sensitivity and specificity. If agreement is poor, the association will be studied on
central reader data using the same methods.
This study should provide a tool to evaluate the ability of endoscopic remission evaluation
in patients in clinical remission to accurately predict sustained clinical remission. If it
is the case, this tool could become the therapeutic objective for patients in clinical
remission with ileal and/or colonic CD. If agreement is satisfactory between local and
central reading, the tool could be used in therapeutic trials, but also in clinical practice.
If this is not the case, the tool should be used in clinical trials using central readings.
