Impact of Anti-cytomegalovirus Treatment in the Management of Relapsing Ulcerative Colitis Requiring Vedolizumab Therapy

Study Overview
=================
Brief Summary
-----------------
Ulcerative Colitis (UC) is an inflammatory bowel disease that can require the use of anti-TNF alpha therapy. When anti-TNF alpha failed to obtain a clinical response, the use of a new anti-integrin therapy, vedolizumab, can be proposed. The efficacy of vedolizumab has been assessed in a phase 3 study (GEMINI I), with response rates of 41.1% with vedolizumab vs 25.5% with placebo. CytoMegaloVirus (CMV) reactivation has been associated with resistance to steroid and to several lines of immunosuppressive therapy. Antiviral therapy was proven to decrease the tissue viral load and to restore the response to immunosuppressive therapies (up to 80% in small group of patients). A recent meta-analysis supports the use of valganciclovir in case of CytoMegaloVirus (CMV) reactivation in active Ulcerative Colitis (UC). Moreover, a study showed that the risk of CMV reactivation seems to be more important with vedolizumab than with anti TNF, and the risk of colectomy is higher in case of CytoMegaloVirus (CMV) reactivation (p<0.05).

Detailed Description
-----------------
The hypothesis of this study is in Ulcerative Colitis (UC) patients with tissue CytoMegaloVirus (CMV) reactivation ; not responding to anti-TNF or without anti-TNF ; a treatment with valganciclovir, added to vedolizumab, could improve the clinical response.

Official Title
-----------------
Impact of Anti-cytomegalovirus (Valganciclovir) Treatment in the Management of Relapsing Ulcerative Colitis (UC) Requiring Vedolizumab Therapy: a Randomized Clinical Trial Comparing a Strategy With or Without Antiviral Therapy.

Conditions
-----------------
Ulcerative Colitis, Unspecified

Intervention / Treatment
-----------------
* Drug: Valganciclovir


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patient with moderate to severe active Ulcerative Colitis (UC) defined by a Mayo score greater than 5 Patient with an inflammatory outbreak of Ulcerative Colitis (UC) : without anti-TNF under anti-TNF (infliximab, adalimumab, golimumab) after induction (no primary response) or clinical recurrence (secondary failure). Having rectosigmoidoscopy with an endoscopic Mayo score≥ 2 with 2 biopsies of the inflammatory tissue Presence of a CytoMegaloVirus (CMV) infection in the inflammatory tissue (viral load greater than 5 IU / 100000 cells by qPCR) Patient with a negative pre-treatment assessment including HIV, HBV, HCV, HCV serology, a negative quantiferon or a history of tuberculosis preventive treatment adapted by Rifinah or Rimifon Signed informed consent Exclusion Criteria: Patient with severe acute colitis Patient treated by ciclosporin or Prograf Patient with Human Immunodeficiency Virus (HIV)+, hepatitis B, hepatitis C, tuberculosis Clostridium difficile infection. Patient with intolerance or contraindications to current therapy Pregnant or starts breastfeeding Patient who received a live vaccine in the month preceding the study Patients with severe renal insufficiency defined by creatinine clearance <30ml/minute, or hemodialysed

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control group<br>Patient will be treated by vedolizumab the standard of care alone. | |
| Experimental: Experimental group<br>Patient will be treated by vedolizumab the standard of care associated at valganciclovir. | Drug: Valganciclovir<br>* The experimental intervention consists of taking the treatment Valganciclovir 900 mg morning and evening for 3 weeks<br>* Other names: antiviral therapy;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical response | Percentage of patients in clinical response. the clinical response is defined by the decrease in the total Mayo Score compared to the inclusion of at least 3 points and at least 30% with a decrease in the score of bleeding (item 2 of the Mayo sub-score) from at least one point or sub-score of bleeding from 0 or 1 point with or without anti-CMV treatment. The Mayo score includes 3 items: stool frequency, presence of blood in the stool, and overall assessment of the disease. | Weeks 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical remission | Percentage of patients in clinical remission defined by a total Mayo score <3 with an endoscopic score <2 and no clinical sub-score> 2. | Weeks 6 | 
| Mucosal healing | Percentage of patients in mucosal healing defined by endoscopic mayo score <2 | Weeks 6 | 
| Viral load CytoMegaloVirus (CMV) | Value of viral load CytoMegaloVirus (CMV) by qPCR on inflammatory tissue in IU / 100000 cells. | Weeks 6 | 
| clinical remission | Percentage of patients in clinical remission defined by a total Mayo score <3 with an endoscopic score <2 and no clinical sub-score> 2. | Weeks 52 | 
| Rate of colectomy | Percentage of patients who required colectomy | Weeks 52 | 
| Adverse effects | Number and severity of adverse effects | Weeks 52 | 
| viral load of the Torque teno virus | performed on the blood tube and tissue biopsies | Week 6 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Ulcerative Colitis (UC), CytoMegaloVirus (CMV), Vedolizumab, Valganciclovir, Anti-TNF, Mayo score