Ganciclovir Resistant Cytomegalovirus Infection in SOT Recipients.

Cytomegalovirus Infections Clinical Trial

Official title:

Epidemiological Burden of and Risk Factors for Ganciclovir Resistant Cytomegalovirus in Solid Organ Transplant Patients: Multicentre Cohort Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05234723
• Other study ID #: ReCySOT
• Status: Not yet recruiting
• Start date: February 1, 2022
• Est. completion date: June 30, 2022

Study information

• Verified date: February 2022
• Source: IRCCS Azienda Ospedaliero-Universitaria di Bologna
• Contact: Renato Pascale, MD
• Phone: +390512143199
• Email: renato.pascale[@]aosp.bo.it
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

ReCySOT study is a multicenter, retrospective, observational case-control study on risk factors for developing a ganciclovir-resistant (GCV-R) cytomegalovirus infection in patients receiving solid organ transplant. Aims of the study are to investigate the incidence of and risk factors for GCV-R CMV infection in SOT recipients in order to design further studies aimed at preventing and improving the patient management of GCV-R CMV infections.

Description:

Cytomegalovirus (CMV) is an important cause of morbidity and mortality in solid organ transplant (SOT) patients. Ganciclovir is the first line therapy for treatment and prevention of CMV infection in SOT recipients, with established efficacy and relatively safe profile.

Ganciclovir-resistant (GCV-R) CMV is an uncommon but frightening clinical problem due to limited, toxic and less effective therapeutic alternative drugs. Indeed, some studies indicate that GCV-R is associated with significant additional attributable morbidity and mortality in SOT recipients compared with ganciclovir susceptible (GCV-S) CMV disease.

Few data are available about the incidence of GCV-R-CMV in SOT patients showing a range from 0% to 3% . The serological mismatch group and the type of SOT have been reported as the main factors influencing such range. Indeed, in one of the largest experience now available, the incidence of GCV-R accounted up to 12% in a cohort of lung transplant recipients.Risk factors for ganciclovir resistance development appear to be the high-risk D+/R- subset, high viral loads, increased durations of antiviral drug exposure and the use of more potent immunosuppression. However, these reports come from small, monocentric experiences with a limited number of cases.

In general, mutations that confer resistance to ganciclovir are not present at baseline but emerge and become amplified over time, especially in the presence of an incompletely suppressive drug exposure. The GCV-R is due to mutations in UL97 and UL54 genes. UL97 mutations confer various degrees of phenotypic resistance to ganciclovir. Mutations in UL54 determine higher-level resistance to ganciclovir and usually appear as a second step after mutations in UL97.

Second-line strategies for the treatment of GCV-R CMV are based on high dose of GCV administration or foscarnet/cidofovir use, both with a high risk of metabolic and renal dysfunction. Alternative strategies are based on the use of adjunctive treatments such as cytomegalovirus immunoglobulins (IVIG), infusions of CMV-specific Tcells or several drugs with indirect anti-CMV action (mTOR inhibitors sirolimus and everolimus, leflunomide and artesunate). Finally, the new antiviral drugs approved for prophylaxis (letermovir) or in advanced clinical development (maribavir, brincidofovir), are reported as anecdotical alternative strategies for the treatment of GCV-R CVM infection. The limited therapeutic strategies for GCV-R CMV treatment highlight the need for new strategies to prevent resistance development.

The investigators carry-out a multicenter retrospective observational study to define incidence of GCV-R CMV-infection in SOT patients and to identify the risk factors for its development in SOT recipients. Data from this study could be useful to design further studies aimed at preventing and improving the patient management of GCV-R CMV infections.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: June 30, 2022
• Est. primary completion date: May 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Diagnosis of CMV infection in adult (age = 18 years) patients underwent SOT

• Ability to understand the purpose of the study and provide signed and dated informed consent

Exclusion Criteria:

• Lack of clinical and/or laboratory data to establish the type of CMV event

• Lack of the serological mismatch at transplantation

• Lack of the type of SOT

• Lack of the patient and graft outcome at 30, 60 or 90 days after CMV event diagnosis.

Related Conditions & MeSH terms

• Cytomegalovirus Infections
• Infections

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
IRCCS Azienda Ospedaliero-Universitaria di Bologna

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To define incidence of GCV-R CMV-infection in SOT patients	To define incidence of GCV-R CMV-infection in SOT patients	Through study completion, an average of 1 year
Primary	To define the risk factors for GCV-R CMV-infection development in SOT patients	To define the risk factors for GCV-R CMV-infection development in SOT patients	Through study completion, an average of 1 year
Secondary	To compare type of CMV episode between SOT patients with GCV-R versus GCV-S CMV-infection.	To compare type of CMV episode: infection or disease (the last cathegorized as CMV syndrome or Tissue invasion) between SOT patients with GCV-R versus GCV-S CMV-infection.	Through study completion, an average of 1 year
Secondary	To compare virological cure between SOT patients with GCV-R versus GCV-S CMV-infection.	To compare virological cure at 30, 60 and 90 days after CMV infection diagnosis and relapse of CMV infection between SOT patients with GCV-R versus GCV-S CMV-infection.	Through study completion, an average of 1 year
Secondary	To compare clinical cure between SOT patients with GCV-R versus GCV-S CMV-infection.	To compare clinical cure at 30, 60 and 90 days after CMV infection diagnosis between SOT patients with GCV-R versus GCV-S CMV-infection.	Through study completion, an average of 1 year
Secondary	To compare graft outcome between SOT patients with GCV-R versus GCV-S CMV-infection.	To compare graft failure rate and the need of re-SOT between SOT patients with GCV-R versus GCV-S CMV-infection between SOT patients with GCV-R versus GCV-S CMV-infection.	Through study completion, an average of 1 year
Secondary	To compare the need of ICU and hospital stay between SOT patients with GCV-R versus GCV-S CMV-infection.	To compare total length of ICU and hospital stay between SOT patients with GCV-R versus GCV-S CMV-infection.	Through study completion, an average of 1 year
Secondary	To compare the need of readmission in ICU and/or hospital between SOT patients with GCV-R versus GCV-S CMV-infection.	To compare the need of readmission in ICU and/or hospital between SOT patients with GCV-R versus GCV-S CMV-infection.	Through study completion, an average of 1 year
Secondary	To compare all cause mortality between SOT patients with GCV-R versus GCV-S CMV-infection.	To compare all-cause mortality during infection episode and follow-up (30, 60, 90 days after the first CMV infection diagnosis) between SOT patients with GCV-R versus GCV-S CMV-infection.	Through study completion, an average of 1 year
Secondary	To describe the therapeutic management of GCV-R CMV-infection.	To describe the therapeutic management of GCV-R CMV-infection.	Through study completion, an average of 1 year
Secondary	To evaluate differences of CMV-specific T-cell response in patients with GCV-R versus GCV-S CMV-infection.	To evaluate differences of CMV-specific T-cell response in patients with GCV-R versus GCV-S CMV-infection. CMV-specific T-cell response will be assesed determining the detection of IFN-? expressed in UI/ml after stimulation of whole blood or peripheral blood mononuclear cells (PBMC) with CMV-specific antigens or overlapping peptides.	Through study completion, an average of 1 year