Determining a Viral Load Threshold for Treating Cytomegalovirus (CMV)
Primary Purpose
Viraemia
Status
Completed
Phase
Phase 4
Locations
United Kingdom
Study Type
Interventional
Intervention
ganciclovir (start when CMV PCR >200copies / ml x2)
Monitor (Treatment starts when CMV PCR >3,000 copies / ml)
Stop treatment when 2 levels CMV PCR <3,000 copies / ml
Monitor (Treatment stops CMV PCR <200 copies / ml x2)
Sponsored by
About this trial
This is an interventional treatment trial for Viraemia focused on measuring Optimising treatment of cytomegalovirus infection
Eligibility Criteria
Inclusion Criteria:
- All Stem Cell, Renal and Liver Transplant recipients.
- Willing to give informed consent.
- For Group A) All patients with CMV viraemia (between 200 and 3000 copies/ml) in the liver, renal and stem cell groups in two consecutive samples & for Group B) Those patients requiring pre-emptive therapy because viral load is > 3,000 copies/ml.
- All patients in either section of the study must be available for CMV PCR monitoring at least twice per week.
Exclusion Criteria:
- Exclusion Criteria
- Profound neutropaenia considered to preclude administration of ganciclovir or profound renal failure considered to preclude administration of foscarnet.
- Inability to give informed consent.
- In the stem cell group, Donor negative, Recipient negative transplants.
- In the stem cell group: matched unrelated donors who are CMV seronegative.
- Those patients who have been in Group A cannot then enter the Group B part. of the study. 5.2.6 Those patients who have been in Group B cannot then enter the Group A part of the study.
Sites / Locations
- Royal Free London NHS Foundation Trust, Royal Free Hospital, Pond Street
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Group A
Group B
Arm Description
Group A: (low level infection) has 2 arms: Start treatment when 2 consecutive levels CMV PCR >200copies / ml Monitor (Treatment starts when CMV PCR >3,000 copies / ml (current site clinical protocol))
Group B: (patients receiving pre-emptive therapy) has 2 arms: Stop treatment when 2 levels CMV PCR <3,000 copies / ml Monitor (Treatment stops when there are 2 consecutive levels of CMV PCR <200 copies / ml (current site clinical protocol))
Outcomes
Primary Outcome Measures
Group A # with low level of CMV who develop a viral load > 3000 copies/ml & Group B # who develop a 2nd episode of a viral load above 3000 copies/ml after therapy stopped.
Secondary Outcome Measures
To define the duration of antiviral therapy needed to treat CMV viraemia. To record the rate of increase in viral load prior to starting preemptive therapy & to correlate viral loads with CMV specific immune function.
Full Information
NCT ID
NCT00947141
First Posted
June 12, 2009
Last Updated
October 25, 2017
Sponsor
University College, London
1. Study Identification
Unique Protocol Identification Number
NCT00947141
Brief Title
Determining a Viral Load Threshold for Treating Cytomegalovirus (CMV)
Official Title
Determining a Viral Load Threshold for Pre-emptive Therapy for Cytomegalovirus Infection in Transplant Patients Using Real Time Polymerase Chain Reaction (PCR) Monitoring
Study Type
Interventional
2. Study Status
Record Verification Date
October 2017
Overall Recruitment Status
Completed
Study Start Date
February 2003 (undefined)
Primary Completion Date
December 2011 (Actual)
Study Completion Date
February 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University College, London
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study aims to determine: a) whether those patients with 'low level' viral load results (between 200 and 3,000 copies/ml) could be monitored as opposed to starting preemptive therapy with valganciclovir, ganciclovir and/or foscarnet; b) whether those patients with 'high level' viral load results (above 3,000 copies/ml) could stop preemptive therapy earlier, thus maximising the benefits of therapy and minimising its risks.
Detailed Description
Background and Study Rationale
In transplant recipients with CMV infection, the risk of developing CMV disease is directly proportional to the CMV DNA viral load. Historically at The Royal Free, Hampstead, patients were given preemptive therapy on the basis of two consecutive positive CMV PCR results as detected by a qualitative PCR technique. With the introduction of real time PCR, using a Taqman probe and the ABI7700 thermal cycler, it is possible to obtain rapid and sensitive results of viral load on clinical samples with a lower limit of detection of 200 copies/ml. Thus, viral load data can be incorporated into the clinical management of the patient.
From our natural history data, it has been shown that patients with CMV disease had a CMV PCR load ranging from 14,000 to 203 million (median 175,500). The lower bound of the 95% confidence limits of this distribution was 37,000 copies/ml and we aimed to initiate therapy in time to prevent CMV viral load reaching this value. To give a margin of safety, bearing in mind the 1 day average doubling-time of CMV and the timing of sampling twice-weekly, we therefore recommended that preemptive therapy be given once the viral load increases above 3,000 copies/ml. In the past, all patients with a CMV PCR load between 200 and 3,000 copies/ml have received preemptive treatment because the previous PCR assay did not give a quantitative result. As treatment is associated with side effects such as neutropaenia (ganciclovir) and renal impairment (foscarnet) it would be preferable to avoid unnecessary exposure where possible. This study aims to determine: a) whether those patients with 'low level' viral load results (between 200 and 3,000 copies/ml) could be monitored as opposed to starting preemptive therapy with valganciclovir, ganciclovir and/or foscarnet; b) whether those patients with 'high level' viral load results (above 3,000 copies/ml) could stop preemptive therapy earlier, thus maximising the benefits of therapy and minimising its risks.
Objectives
Primary Objectives
To define the number of patients in Group A with a low level of CMV reactivation who subsequently develop a viral load greater than 3000 copies/ml.
To define the number of patients in Group B who develop a second episode of a viral load above 3000 copies/ml after therapy has been discontinued at the defined viral load cut-offs.
Secondary Objectives
To define the duration of antiviral therapy needed to treat CMV viraemia.
To record the rate of increase in viral load prior to starting preemptive therapy.
To correlate viral loads with CMV specific immune function.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Viraemia
Keywords
Optimising treatment of cytomegalovirus infection
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
165 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group A
Arm Type
Experimental
Arm Description
Group A: (low level infection) has 2 arms:
Start treatment when 2 consecutive levels CMV PCR >200copies / ml
Monitor (Treatment starts when CMV PCR >3,000 copies / ml (current site clinical protocol))
Arm Title
Group B
Arm Type
Experimental
Arm Description
Group B: (patients receiving pre-emptive therapy) has 2 arms:
Stop treatment when 2 levels CMV PCR <3,000 copies / ml
Monitor (Treatment stops when there are 2 consecutive levels of CMV PCR <200 copies / ml (current site clinical protocol))
Intervention Type
Drug
Intervention Name(s)
ganciclovir (start when CMV PCR >200copies / ml x2)
Other Intervention Name(s)
valganciclovir, foscarnet
Intervention Description
Group A: Start ganciclovir when CMV PCR >200copies / ml x 2) . Participants are randomised to either Monitor or Treat. If monitored, treatment will only begin if viral load has increased > 3,000. If treated (and monitored) treat until <200 copies on 2 consecutive occasions.
Routine standard of care would include treatment of Valganciclovir 900mg Tablet BD (dose adjusted for renal impairment), Ganciclovir 5mg/kg BD IV, or Foscarnet 60mg/kg according to randomisation within Group A or Group B
Intervention Type
Other
Intervention Name(s)
Monitor (Treatment starts when CMV PCR >3,000 copies / ml)
Other Intervention Name(s)
valganciclovir, foscarnet
Intervention Description
Group A: CMV viral load between 200-3,000 copies/ml (on 2 occasions). Participants are randomised to either Monitor or Treat. If monitored, treatment will only begin if viral load has increased > 3,000. If treated (and monitored) treat until <200 copies on 2 consecutive occasions.
Routine standard of care would include treatment of Valganciclovir 900mg Tablet BD (dose adjusted for renal impairment), Ganciclovir 5mg/kg BD IV, or Foscarnet 60mg/kg according to randomisation within Group A or Group B
Intervention Type
Drug
Intervention Name(s)
Stop treatment when 2 levels CMV PCR <3,000 copies / ml
Other Intervention Name(s)
valganciclovir, foscarnet
Intervention Description
Group B: Viral load > 3,000 copies/ml. Participants are randomised to treat until < 3,000 copies/ml on 2 occasions or treat until <200 copies/ml on 2 consecutive occasions.
Routine standard of care would include treatment of Valganciclovir 900mg Tablet BD (dose adjusted for renal impairment), Ganciclovir 5mg/kg BD IV, or Foscarnet 60mg/kg according to randomisation within Group A or Group B
Intervention Type
Other
Intervention Name(s)
Monitor (Treatment stops CMV PCR <200 copies / ml x2)
Other Intervention Name(s)
valganciclovir, foscarnet
Intervention Description
Group B: Viral load > 3,000 copies/ml. Participants are randomised to treat until < 3,000 copies/ml on 2 occasions or treat until <200 copies/ml on 2 consecutive occasions.
Routine standard of care would include treatment of Valganciclovir 900mg Tablet BD (dose adjusted for renal impairment), Ganciclovir 5mg/kg BD IV, or Foscarnet 60mg/kg according to randomisation within Group A or Group B
Primary Outcome Measure Information:
Title
Group A # with low level of CMV who develop a viral load > 3000 copies/ml & Group B # who develop a 2nd episode of a viral load above 3000 copies/ml after therapy stopped.
Time Frame
At study completion
Secondary Outcome Measure Information:
Title
To define the duration of antiviral therapy needed to treat CMV viraemia. To record the rate of increase in viral load prior to starting preemptive therapy & to correlate viral loads with CMV specific immune function.
Time Frame
At study completion
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
All Stem Cell, Renal and Liver Transplant recipients.
Willing to give informed consent.
For Group A) All patients with CMV viraemia (between 200 and 3000 copies/ml) in the liver, renal and stem cell groups in two consecutive samples & for Group B) Those patients requiring pre-emptive therapy because viral load is > 3,000 copies/ml.
All patients in either section of the study must be available for CMV PCR monitoring at least twice per week.
Exclusion Criteria:
Exclusion Criteria
Profound neutropaenia considered to preclude administration of ganciclovir or profound renal failure considered to preclude administration of foscarnet.
Inability to give informed consent.
In the stem cell group, Donor negative, Recipient negative transplants.
In the stem cell group: matched unrelated donors who are CMV seronegative.
Those patients who have been in Group A cannot then enter the Group B part. of the study. 5.2.6 Those patients who have been in Group B cannot then enter the Group A part of the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Professor Paul D Griffiths, MD DSc
Organizational Affiliation
University College, London
Official's Role
Principal Investigator
Facility Information:
Facility Name
Royal Free London NHS Foundation Trust, Royal Free Hospital, Pond Street
City
London
ZIP/Postal Code
NW3 2QG
Country
United Kingdom
12. IPD Sharing Statement
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Determining a Viral Load Threshold for Treating Cytomegalovirus (CMV)
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