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

Ulcerative Colitis, Unspecified Clinical Trial

— CYTOVEDO  

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.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04064697
• Other study ID #: 18PH192
• Secondary ID: 2019-001032-54
• Status: Terminated
• Phase: Phase 3
• Start date: April 22, 2021
• Est. completion date: February 8, 2024

Study information

• Verified date: June 2023
• Source: Centre Hospitalier Universitaire de Saint Etienne
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 6
• Est. completion date: February 8, 2024
• Est. primary completion date: November 23, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis, Unspecified

Intervention

Drug:
• Valganciclovir
The experimental intervention consists of taking the treatment Valganciclovir 900 mg morning and evening for 3 weeks

Locations

Country	Name	City	State
France	CH d'Annecy	Annecy
France	CHU de Clermont-Ferrand	Clermont-Ferrand
France	CHU de Lyon Sud	Lyon
France	CHU de Montpellier	Montpellier
France	CHU de Nice	Nice
France	APHP - Hôpital Saint-Antoine	Paris
France	CHU ROUEN - Service Gastro-entérologie	Rouen
France	CHU de Saint Etienne	Saint-Étienne

Sponsors (2)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Saint Etienne	Ministry of Health, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Mucosal healing	Percentage of patients in mucosal healing defined by endoscopic mayo score <2	Weeks 6
Secondary	Viral load CytoMegaloVirus (CMV)	Value of viral load CytoMegaloVirus (CMV) by qPCR on inflammatory tissue in IU / 100000 cells.	Weeks 6
Secondary	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
Secondary	Rate of colectomy	Percentage of patients who required colectomy	Weeks 52
Secondary	Adverse effects	Number and severity of adverse effects	Weeks 52
Secondary	viral load of the Torque teno virus	performed on the blood tube and tissue biopsies	Week 6