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

Centre Hospitalier Universitaire de Saint Etienne

Status and phase: Terminated; Phase 3

Conditions: Ulcerative Colitis, Unspecified

Treatments: Drug: Valganciclovir

Study type: Interventional

Funder types: Other

Identifiers

NCT04064697

2019-001032-54 (EudraCT Number)

18PH192

Details and patient eligibility

About

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).

Full 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.

Enrollment: 6 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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6 participants in 2 patient groups

Control group

No Intervention group

Description:

Patient will be treated by vedolizumab the standard of care alone.

Experimental group

Experimental group

Description:

Patient will be treated by vedolizumab the standard of care associated at valganciclovir.

Treatment:

Drug: Valganciclovir