Determining a Viral Load Threshold for Treating Cytomegalovirus (CMV)
Recruitment status was Recruiting
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.
Drug: ganciclovir treatment or monitoring of viral load.
Other: Monitor or treat with ganciclovir
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Determining a Viral Load Threshold for Pre-emptive Therapy for Cytomegalovirus Infection in Transplant Patients Using Real Time PCR Monitoring|
- 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 ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
|Study Start Date:||February 2003|
|Estimated Study Completion Date:||August 2011|
|Estimated Primary Completion Date:||February 2011 (Final data collection date for primary outcome measure)|
Experimental: Group A & Group B
Group A: (low level infection) Group B: (patients receiving pre-emptive therapy)
Drug: ganciclovir treatment or monitoring of viral load.
Other Name: valganciclovir or foscarnetOther: Monitor or treat with ganciclovir
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.
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
Other Name: valganciclovir or foscarnet
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.
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00947141
|Contact: Professor Paul D Griffiths, MD DSc||+44 (0) 207 830 email@example.com|
|The Royal Free Hampstead, London. UK.||Recruiting|
|Hampstead, London, United Kingdom, NW3 2QG|
|Contact: Paul D Griffiths, MD DSc +44 (0)207 830 2997 firstname.lastname@example.org|
|Contact: Anna G Stanton, BSc +44 (O)207 794 0500 ext 34943 Anna.Stanton@royalfree.nhs.uk|
|Principal Investigator: Paul D Griffiths, MD DSc|
|Principal Investigator:||Professor Paul D Griffiths, MD DSc||University College, London|