Determining a Viral Load Threshold for Treating Cytomegalovirus (CMV)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2009 by Royal Free Hampstead NHS Trust.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Royal Free Hampstead NHS Trust
ClinicalTrials.gov Identifier:
NCT00947141
First received: June 12, 2009
Last updated: July 27, 2010
Last verified: July 2009
  Purpose

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.


Condition Intervention Phase
Cytomegalovirus
Drug: ganciclovir treatment or monitoring of viral load.
Other: Monitor or treat with ganciclovir
Phase 4

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Royal Free Hampstead NHS Trust:

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. [ Time Frame: At study completion ] [ Designated as safety issue: No ]

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. [ Time Frame: At study completion ] [ Designated as safety issue: No ]

Estimated Enrollment: 178
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)
Arms Assigned Interventions
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.
ganciclovir iv.
Other Name: valganciclovir or foscarnet
Other: 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

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

  1. 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.
  2. 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

  1. To define the duration of antiviral therapy needed to treat CMV viraemia.
  2. To record the rate of increase in viral load prior to starting preemptive therapy.
  3. To correlate viral loads with CMV specific immune function.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. All Stem Cell, Renal and Liver Transplant recipients.
  2. Willing to give informed consent.
  3. 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.
  4. All patients in either section of the study must be available for CMV PCR monitoring at least twice per week.

Exclusion Criteria:

  1. Exclusion Criteria
  2. Profound neutropaenia considered to preclude administration of ganciclovir or profound renal failure considered to preclude administration of foscarnet.
  3. Inability to give informed consent.
  4. In the stem cell group, Donor negative, Recipient negative transplants.
  5. In the stem cell group: matched unrelated donors who are CMV seronegative.
  6. 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00947141

Contacts
Contact: Professor Paul D Griffiths, MD DSc +44 (0) 207 830 2997 p.griffiths@medsch.ucl.ac.uk

Locations
United Kingdom
The Royal Free Hampstead, London. UK. Recruiting
Hampstead, London, United Kingdom, NW3 2QG
Contact: Paul D Griffiths, MD DSc    +44 (0)207 830 2997    p.griffiths@medsch.ucl.ac.uk   
Contact: Anna G Stanton, BSc    +44 (O)207 794 0500 ext 34943    Anna.Stanton@royalfree.nhs.uk   
Principal Investigator: Paul D Griffiths, MD DSc         
Sponsors and Collaborators
Royal Free Hampstead NHS Trust
Investigators
Principal Investigator: Professor Paul D Griffiths, MD DSc University College, London
  More Information

No publications provided

Responsible Party: Professor P D Griffiths MD DSc, Centre for Virology, Royal Free and University College Medical School
ClinicalTrials.gov Identifier: NCT00947141     History of Changes
Other Study ID Numbers: 6077, REC # 6077, Royal Free R and D # 5219, EudraCT 2007-003472-19
Study First Received: June 12, 2009
Last Updated: July 27, 2010
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Royal Free Hampstead NHS Trust:
Optimising treatment of cytomegalovirus infection

Additional relevant MeSH terms:
Cytomegalovirus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Foscarnet
Phosphonoacetic Acid
Ganciclovir
Valganciclovir
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents

ClinicalTrials.gov processed this record on July 24, 2014