Clinical trial NCT04064697: Impact of Anti-cytomegalovirus Treatment in the Management of Relapsing Ulcerative Colitis Requiring Vedolizumab Therapy
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.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Ulcerative Colitis, Unspecified
Keywords: Ulcerative Colitis (UC)
CytoMegaloVirus (CMV)
Vedolizumab
Valganciclovir
Anti-TNF
Mayo score
Lead sponsor: Centre Hospitalier Universitaire de Saint Etienne
Sponsor class: OTHER
Collaborators: name: Ministry of Health, France
First posted: 2019-08-22
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Clinical response
timeFrame: Weeks 6
Secondary outcomes:
measure: Clinical remission
timeFrame: Weeks 6
measure: Mucosal healing
timeFrame: Weeks 6
measure: Viral load CytoMegaloVirus (CMV)
timeFrame: Weeks 6
measure: clinical remission
timeFrame: Weeks 52
measure: Rate of colectomy
timeFrame: Weeks 52
measure: Adverse effects
timeFrame: Weeks 52
measure: viral load of the Torque teno virus
timeFrame: Week 6
Other outcomes:
Locations:
city: Annecy
country: France
facility: CH d'Annecy
city: Clermont-Ferrand
country: France
facility: CHU de Clermont-Ferrand
city: Lyon
country: France
facility: CHU de Lyon Sud
city: Montpellier
country: France
facility: CHU de Montpellier
city: Nice
country: France
facility: CHU de Nice
city: Paris
country: France
facility: APHP - Hôpital Saint-Antoine
city: Rouen
country: France
facility: CHU ROUEN - Service Gastro-entérologie
city: Saint-Étienne
country: France
facility: CHU de Saint Etienne
Study officials:
affiliation: CHU SAINT-ETIENNE
name: Pauline VEYRARD, MD
role: PRINCIPAL_INVESTIGATOR
References: