A Study on Cytomegalovirus (CMV) Infection Outcomes Among Solid Organ Transplant (SOT) Participants in Europe and Canada

NCT05576805 | Completed

• 1 other identifier: TAK-620-4003
• Study Type: observational
• Target: 159
• Locations: 9 countries
• Sites: 15

Brief Summary

The main aim of the study is to assess the clinical outcomes of current CMV management across different regions of the world (Europe \[EU\] and Canada \[CAN\]). Data will be collected retrospectively from medical charts. No study medicines will be provided to participants in this study.

Conditions

Cytomegalovirus (CMV)

Outcome Measures

Primary Outcomes (22)

• Time from Solid Organ Transplant (SOT) Until Start Date of the Symptomatic or Asymptomatic Index Episode

  Index episode is first CMV episode in which the participant is considered RRI to anti-CMV treatment or had CMV viremia and received pre-emptive treatment, without becoming RRI during that episode. Symptomatic episode is an episode wherein there is "Tissue invasive/end organ disease" or "CMV syndrome" at any time, and asymptomatic when there is no such observation.

  From SOT up to start date of the index episode (Up to 7 years 3 months)

• Percentage of Participants who are Asymptomatic and Symptomatic at the Index and Recurrent Episodes

  Index episode is first CMV episode in which the participant is considered RRI to anti-CMV treatment or had CMV viremia and received pre-emptive treatment, without becoming RRI during that episode. Recurrent episodes is defined as new CMV infection in a participant with previous evidence of CMV infection. Symptomatic episode is an episode wherein there is "Tissue invasive/end organ disease" or "CMV syndrome" at any time, and asymptomatic when there is no such observation.

  Up to 7 years 3 months

• Percentage of Participants With CMV Viremia Clearance as Defined by Site Investigator at the Index Episode and for Recurrent Episodes

  Index episode is first CMV episode in which the participant is considered RRI to anti-CMV treatment or had CMV viremia and received pre-emptive treatment, without becoming RRI during that episode. Recurrent episodes is defined as new CMV infection in a participant with previous evidence of CMV infection. CMV viremia clearance is defined as when an active CMV viremia can be considered cleared from the participant, as determined by the site investigator.

  Up to 7 years 3 months

• Time From Start of Index Episode to CMV Viremia Clearance as Defined by Site Investigator

  Index episode is first CMV episode in which the participant is considered RRI to anti-CMV treatment or had CMV viremia and received pre-emptive treatment, without becoming RRI during that episode. CMV viremia clearance is defined as when an active CMV viremia can be considered cleared from the participant, as determined by the site investigator.

  From start of index episode to CMV viremia clearance (Up to 7 years 3 months)

• Percentage of Participants With CMV Viremia Clearance as Defined by Site Investigator at Week 8 After Index Date

  Index date is the date when participant was considered resistant, refractory or intolerant to anti-CMV treatment for the first time after transplant (RRI CMV index date) or pre-emptive treatment for the first time after transplant following CMV viremia (CMV preemptive treatment index date). CMV viremia clearance is defined as when an active CMV viremia can be considered cleared from the participant, as determined by the site investigator. The assessment will be based on Kaplan-Meier estimate.

  At Week 8 after index date

• Percentage of Participants With CMV Viremia Clearance as Defined by Site Investigator at Week 20 After Index Date

  Index date is the date when participant was considered resistant, refractory or intolerant to anti-CMV treatment for the first time after transplant (RRI CMV index date) or pre-emptive treatment for the first time after transplant following CMV viremia (CMV preemptive treatment index date). CMV viremia clearance is defined as when an active CMV viremia can be considered cleared from the participant, as determined by the site investigator. The assessment will be based on Kaplan-Meier estimate.

  At Week 20 after index date

• Percentage of Participants With CMV Viremia Clearance as Defined by Site Investigator at 1-year After Index Date

  Index date is the date when participant was considered resistant, refractory or intolerant to anti-CMV treatment for the first time after transplant (RRI CMV index date) or pre-emptive treatment for the first time after transplant following CMV viremia (CMV preemptive treatment index date). CMV viremia clearance is defined as when an active CMV viremia can be considered cleared from the participant, as determined by the site investigator. The assessment will be based on Kaplan-Meier estimate. Non-detectable CMV is defined as highest minimum detectable level of CMV assays across all sites.

  At 1-year after index date

• Percentage of Participants With Non-detectable CMV During the Index Episode Prior to and After the Index Date

  Index episode is first CMV episode in which the participant is considered RRI to anti-CMV treatment or had CMV viremia and received pre-emptive treatment, without becoming RRI during that episode. Index date is the date when participant was considered resistant, refractory or intolerant to anti-CMV treatment for the first time after transplant (RRI CMV index date) OR pre-emptive treatment for the first time after transplant following CMV viremia (CMV preemptive treatment index date). The assessment will be based on Kaplan-Meier estimate.

  Up to 7 years 3 months

• Percentage of Participants With Evidence of Non-detectable CMV at Week 8 After Index Date

  Index date is the date when participant was considered resistant, refractory or intolerant to anti-CMV treatment for the first time after transplant (RRI CMV index date) or pre-emptive treatment for the first time after transplant following CMV viremia (CMV preemptive treatment index date). Non-detectable CMV is defined as highest minimum detectable level of CMV assays across all transplant sites. The assessment will be based on Kaplan-Meier estimate.

  At Week 8 after index date

• Percentage of Participants With Evidence of Non-detectable CMV at Week 20 After Index Date

  Index date is the date when participant was considered resistant, refractory or intolerant to anti-CMV treatment for the first time after transplant (RRI CMV index date) or pre-emptive treatment for the first time after transplant following CMV viremia (CMV preemptive treatment index date). Non-detectable CMV is defined as highest minimum detectable level of CMV assays across all transplant sites. The assessment will be based on Kaplan-Meier estimate.

  At Week 20 after index date

• Percentage of Participants With Evidence of Non-detectable CMV at 1-year After Index Date

  Index date is the date when participant was considered resistant, refractory or intolerant to anti-CMV treatment for the first time after transplant (RRI CMV index date) or pre-emptive treatment for the first time after transplant following CMV viremia (CMV preemptive treatment index date). Non-detectable CMV is defined as highest minimum detectable level of CMV assays across all transplant sites.

  At 1-year after index date

• Time From Treatment Initiation to CMV Viremia Clearance as Defined by Site Investigator at the Index Episode

  Index episode is first CMV episode in which the participant is considered RRI to anti-CMV treatment or had CMV viremia and received pre-emptive treatment, without becoming RRI during that episode. CMV viremia clearance is defined as when an active CMV viremia can be considered cleared from the participant, as determined by the site investigator.

  From Treatment Initiation to CMV Viremia Clearance (Up to 7 years 3 months)

• Time From Treatment Initiation Until Evidence of Non-detectable CMV at the Index Episode

  Index episode is first CMV episode in which the participant is considered RRI to anti-CMV treatment or had CMV viremia and received pre-emptive treatment, without becoming RRI during that episode. Non-detectable CMV is defined as highest minimum detectable level of CMV assays across all sites.

  Time from treatment initiation until evidence of non-detectable CMV (Up to 7 years 3 months)

• Time from Start of Index Episode to First Symptomatic CMV Diagnosis

  Index episode is first CMV episode in which the participant is considered RRI to anti-CMV treatment or had CMV viremia and received pre-emptive treatment, without becoming RRI during that episode. Symptomatic CMV is defined CMV-related tissue invasive disease or CMV syndrome.

  From start of index episode to first symptomatic CMV diagnosis (Up to 7 years 3 months)

• Time From Stop Date of the Index Episode to First Recurrent Asymptomatic and Symptomatic CMV Viremia

  Index episode is first CMV episode in which the participant is considered RRI to anti-CMV treatment or had CMV viremia and received pre-emptive treatment, without becoming RRI during that episode. Recurrent episodes is defined as new CMV infection in a participant with previous evidence of CMV infection.

  From stop date of the index episode to first recurrent asymptomatic and symptomatic CMV viremia (Up to 7 years 3 months)

• Percentage of Participants With Anti-CMV Treatment-related Myelosuppression and Nephrotoxicity

  Index episode is first CMV episode in which the participant is considered RRI to anti-CMV treatment or had CMV viremia and received pre-emptive treatment, without becoming RRI during that episode. Percentage of participants with anti-CMV treatment-related myelosuppression each type and nephrotoxicity overall and during the index episode will be reported.

  Up to 7 years 3 months

• Percentage of Participants With Organ Rejection From SOT

  Organ rejection will include overall and by type (acute, chronic or both for T-cell and anti-body mediated).

  Up to 7 years 3 months

• Percentage of Participants With Graft Loss From SOT and the Index Date

  Index date is the date when participant was considered resistant, refractory or intolerant to anti-CMV treatment for the first time after transplant (RRI CMV index date) or pre-emptive treatment for the first time after transplant following CMV viremia (CMV preemptive treatment index date. Graft loss is defined as lack of a functioning graft attributable to infection, immunological response in the organ recipient, recurrent disease, or recurrent underlying disease as described in the physician notes.

  Up to 7 years 3 months

• Percentage of Participants who Died due to any Cause From SOT and Index Date

  Index date is the date when participant was considered resistant, refractory or intolerant to anti-CMV treatment for the first time after transplant (RRI CMV index date) or pre-emptive treatment for the first time after transplant following CMV viremia (CMV preemptive treatment index date, Percentage of participants who died due to any cause from sot and from the index date will be reported.

  Up to 7 years 3 months

• Percentage of Participants who Died due to CMV Infection From SOT and Index Date

  Index date is the date when participant was considered resistant, refractory or intolerant to anti-CMV treatment for the first time after transplant (RRI CMV index date) or pre-emptive treatment for the first time after transplant following CMV viremia (CMV preemptive treatment index date. Percentage of participants who died due to CMV infection from SOT and the index date will be reported.

  Up to 7 years 3 months

• Number of Genetic Mutations Conferring Anti-CMV Resistance From SOT and Index Date

  Index date is the date when participant was considered resistant, refractory or intolerant to anti-CMV treatment for the first time after transplant (RRI CMV index date) or pre-emptive treatment for the first time after transplant following CMV viremia (CMV preemptive treatment index date. Genetic mutation includes UL27, UL54, UL56, UL97, other, unknown mutation. Number of genetic mutations conferring anti-CMV resistance from SOT and at index date will be reported.

  Up to 7 years 3 months

• Percentage of Participants With a Genetic Mutation Conferring Anti-CMV Resistance From SOT at the Index Date

  Index date is the date when participant was considered resistant, refractory or intolerant to anti-CMV treatment for the first time after transplant (RRI CMV index date) or pre-emptive treatment for the first time after transplant following CMV viremia (CMV preemptive treatment index date. Genetic mutation includes UL27, UL54, UL56, UL97, other, unknown mutation. Percentage of participants with genetic mutations conferring anti-CMV resistance from SOT at index date will be reported.

  Up to 7 years 3 months

Secondary Outcomes (20)

• Percentage of Participants With Anti-CMV Primary or Secondary Prophylaxis and Preemptive Treatment

  Up to 7 years 3 months

• Number of Anti-CMV Therapies Used for Primary or Secondary Prophylaxis and Preemptive Treatment

  Up to 7 years 3 months

• Duration of Anti-CMV Prophylaxis Therapy

  Up to 7 years 3 months

• Percentage of Participants With Mono-therapy and Dual-therapy of Anti-CMV Agents of Interest During CMV Episodes

  Up to 7 years 3 months

• Number of Individual and Dual-therapy of Anti-CMV Agents Used During CMV Episodes

  Up to 7 years 3 months

Study Arms (2)

Cohort 1: Resistant, Refractory, or Intolerant (RRI) to Anti-CMV Treatment

Participants who had an SOT after January 1, 2016 and must have developed post-transplant CMV infection and were subsequently characterized as RRI to currently available anti-CMV treatment at least 12 months before enrollment in the study will be observed in this retrospective study for 24 months.

Cohort 2: Pre-emptive CMV Treatment

Participants who had an SOT after January 1, 2019, and who were preemptively treated for CMV at least 12 months before enrollment in the study will be observed in this retrospective study for 24 months.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Participants who had a CMV infection treated with at least one anti-CMV agent and considered resistant, refractory, or intolerant to a currently available agent will be enrolled in Cohort 1 and participants who received pre-emptive therapy for CMV viremia will be enrolled in Cohort 2.

You may qualify if:

• (Cohort 1) Resistant / Refractory or Intolerant:
• Aged greater than or equal to (\>=) 18 years at the time of the SOT.
• Received an SOT after January 1, 2016.
• Diagnosed with asymptomatic or symptomatic CMV infection any time after the SOT date.
• Required \>=1 anti-CMV agent to manage CMV infection and were subsequently considered:
• resistant to currently available anti-CMV agent; OR
• refractory to currently available anti-CMV agent; OR
• intolerant to currently available anti-CMV agent.
• Follow-up information is available for at least 12 months from the index date (that is, date when the participant was first considered resistant, refractory or intolerant to anti-CMV agent) or death, whichever occurs first.
• Provided written informed consent prior to the initiation of any study procedures (unless waiver was granted by the Institutional Ethical Committee \[IEC\]).
• (Cohort 2) Pre-emptive treatment for CMV viremia:
• Aged \>=18 years at the time of the SOT.
• Received an SOT after January 1, 2019.
• Diagnosed with CMV viremia any time after the SOT date and received pre-emptive anti-CMV agent.
• Follow-up information is available for at least 12 months from the index date (that is, date when the participant was first preemptively treated with an anti-CMV agent) or death, whichever occurs first.

You may not qualify if:

• Diagnosed as being positive for human immunodeficiency virus before the SOT.
• Unable to demonstrate a minimum of 12 months of follow-up from the index date (example, incomplete information on dates showing follow-up time).
• Participation in a clinical trial related to CMV treatment during the study period .

Sponsors & Collaborators

• Takeda: lead

Study Sites (15)

MU Graz

Graz, 8036, Austria

Location

MU Innsbruck

Innsbruck, 6020, Austria

Location

UZ Leuven

Leuven, 3000, Belgium

Location

Vancouver GH (VCH)

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Aristotle USM

Thessaloniki, 541 24, Greece

Location

Rabin Medical Center

Petah Tikva, 49100, Israel

Location

U Parma

Parma, 43126, Italy

Location

FP Vergata

Roma, 00133, Italy

Location

U Insubria

Varese, 21100, Italy

Location

Erasmus UMC

Rotterdam, 3015 GD, Netherlands

Location

UMC Utrech

Utrecht, 3584 CX, Netherlands

Location

UCC Gdansk

Gdansk, 80-952, Poland

Location

MU Warsaw

Warsaw, 02-097, Poland

Location

Karolinska UH

Solna, 171 64, Sweden

Location

Uppsala UH

Uppsala, 751 85, Sweden

Location

Related Links

• To obtain more information on the study, click here/on this link

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 10, 2022
• First Posted: October 13, 2022
• Study Start: June 19, 2023
• Primary Completion: March 31, 2024
• Study Completion: March 31, 2024
• Last Updated: April 25, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/ For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

AU (2); IL (1); PL (2); SE (2); CA (1); GR (1); IT (3); BE (1); NL (2)