Cell Mediated Immunity for Secondary Prophylaxis in CMV SOT Patients (Q-CMV)

Cell Mediated Immunity as a Guide for Secondary Prophylaxis in SOT Patients With CMV Infection

This study will evaluate whether a test for Cytomegalovirus (CMV) specific cell-mediated immunity can be used to determine whether patients who complete a course of therapy for CMV viremia need secondary antiviral prophylaxis. Subjects that have negative CMV CMI will receive antiviral prophylaxis for 2 months and those with positive CMV CMI will have their prophylaxis stopped.

Study Overview

• Status: Completed
• Conditions: Cytomegalovirus Viraemia
• Intervention / Treatment: Drug: Valganciclovir or Ganciclovir

Detailed Description

Cytomegalovirus (CMV) is the most important infection in transplant patients and it is a common cause of illness in patients who have undergone a transplant. Serious infections due to CMV can affect many parts of the body including the lungs, the gut, and the liver; when CMV infection becomes serious enough to cause symptoms, it is called CMV disease. Some patients require treatment while others will clear the virus on their own.

QuantiFERON-CMV (QFT-CMV) is a blood test that measures CMV-specific cell-mediated immunity. This test was able to predict that patients with low cell-mediated immunity are at greater risk for developing CMV disease. In this study, QFT-CMV will be used to make a decision regarding CMV treatment. The QFT-CMV test will be performed at the first detection of CMV, at end of antiviral therapy and one month post-therapy. The end-of-therapy results will be available to clinicians and study investigators within one week of collection. Based on the result, a decision will be made to continue with prolonged antiviral therapy. Patients that show weak cell-mediated immunity against CMV will be given secondary antiviral prophylaxis, while patients with good cell-mediated immunity will have their therapy stopped. Patients will continue to be monitored three months after the last QFT-CMV test for recurrent CMV viremia.

This study will also attempt to evaluate the predictive value of the QuantiFERON-Monitor (QFT-Monitor) assay. QFT-Monitor is a recently developed non-pathogen specific immune assay: it is based on immune activation of both innate and adaptive immunity. The investigators hypothesize that stimulation of both the innate and adaptive immunity may predict global immune function and also be predictive of CMV reactivation. The investigators plan to perform the QFT-Monitor assay in parallel to the QFT-CMV test to determine the test characteristics and cut-off values in predicting global immune function. This test will be collected and tested in batches. Therefore, the results will not influence clinical decisions.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G2N2
      • University Health Network, Toronto General Hospital, Multi-Organ Transplant

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult solid organ transplant (SOT) recipient on at least one immunosuppressive medication
• Starting therapy for new onset asymptomatic CMV viremia OR starting therapy for new onset CMV disease
• CMV viral load ≥ 1000 IU/mL

Exclusion Criteria:

• Known ganciclovir-resistant CMV
• Known intolerance to valganciclovir or ganciclovir
• Unable to comply with protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Low CMV CMI; Patients that show low levels of cell-mediated immunity against CMV will have their antiviral therapy (oral Valganciclovir or Intravenous Ganciclovir) continued for an additional 2 months at half dose.	Drug: Valganciclovir or Ganciclovir
No Intervention: High CMV CMI; Patients that show high levels of cell-mediated immunity against CMV will have their antiviral therapy (oral Valganciclovir or Intravenous Ganciclovir) stopped.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Virologic recurrence or disease recurrence	6 months

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Investigators: Principal Investigator: Atul Humar, MD, University Health Network, Toronto

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2014
• Primary Completion (Actual): September 1, 2016
• Study Completion (Actual): June 16, 2017

Study Registration Dates

• First Submitted: February 18, 2015
• First Submitted That Met QC Criteria: February 24, 2015
• First Posted (Estimate): February 25, 2015

Study Record Updates

• Last Update Posted (Actual): September 21, 2017
• Last Update Submitted That Met QC Criteria: September 20, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: Quantiferon-CMV; Quantiferon-Monitor; Solid Organ Transplants; CMV Disease
• Additional Relevant MeSH Terms: Pathologic Processes; Virus Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Viremia; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Valganciclovir; Ganciclovir; Ganciclovir triphosphate
• Other Study ID Numbers: UHN-CMV-001