ViraemiaPhase 4NCT00947141
Determining a Viral Load Threshold for Treating Cytomegalovirus (CMV)
A Phase 4 study testing ganciclovir (start when CMV PCR >200copies / ml x2), Monitor (Treatment starts when CMV PCR >3,000 copies / ml) and Stop treatment when 2 levels CMV PCR <3,000 copies / ml in people with Viraemia, run by University College, London at 1 site in United Kingdom.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Viraemia
- What is being tested?
- ganciclovir (start when CMV PCR >200copies / ml x2), Monitor (Treatment starts when CMV PCR >3,000 copies / ml) and Stop treatment when 2 levels CMV PCR <3,000 copies / ml
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 165 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Feb 2003to Feb 2013
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Royal Free London NHS Foundation Trust, Royal Free Hospital, Pond Street
London, NW3 2QG
About this study
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
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.
Read the 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.
- Conditions
- Viraemia
- Being tested
- 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)
- Keywords
- Optimising treatment of cytomegalovirus infection
- Medical subject headings
- Viremia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ganciclovir (start when CMV PCR >200copies / ml x2)Drug
Also called valganciclovir, foscarnet
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
Monitor (Treatment starts when CMV PCR >3,000 copies / ml)Other
Also called valganciclovir, foscarnet
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
Stop treatment when 2 levels CMV PCR <3,000 copies / mlDrug
Also called valganciclovir, foscarnet
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
Monitor (Treatment stops CMV PCR <200 copies / ml x2)Other
Also called valganciclovir, foscarnet
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
| Study group | Role | What they receive |
|---|---|---|
| Group A | Experimental | Group A: (low level infection) has 2 arms:
1. Start treatment when 2 consecutive levels CMV PCR >200copies / ml
2. Monitor (Treatment starts when CMV PCR >3,000 copies / ml (current site clinical protocol)) Receives: Drug: ganciclovir (start when CMV PCR >200copies / ml x2); Other: Monitor (Treatment starts when CMV PCR >3,000 copies / ml) |
| Group B | Experimental | Group B: (patients receiving pre-emptive therapy) has 2 arms:
1. Stop treatment when 2 levels CMV PCR <3,000 copies / ml
2. Monitor (Treatment stops when there are 2 consecutive levels of CMV PCR <200 copies / ml (current site clinical protocol)) Receives: Drug: Stop treatment when 2 levels CMV PCR <3,000 copies / ml; Other: Monitor (Treatment stops CMV PCR <200 copies / ml x2) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: At study completion
Secondary outcomes (1)
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.
Measured: At study completion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2009 (estimated)
- Study startFeb 2003
- Primary completionDec 2011
- Study completionFeb 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for ViraemiaStudies of the same condition, open and under way.
- More trials run by University College, LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 165 participants (actual)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Professor Paul D Griffiths, MD DSc, Principal investigator, University College, London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00947141
- Sponsor's protocol ID
- 6077
- Other IDs
- REC # 6077, Royal Free R and D # 5219, ISRCTN03307563
- Status last verified
- Oct 2017
- First submitted
- 12 Jun 2009
- Last updated
- 27 Oct 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Vernooij RW, Michael M, Colombijn JM, Owers DS, Webster AC, Strippoli GF, Hodson EM. Pre-emptive treatment for cytomegalovirus viraemia to prevent cytomegalovirus disease in solid organ transplant recipients. Cochrane Database Syst Rev. 2025 Jan 14;1(1):CD005133. doi: 10.1002/14651858.CD005133.pub4.
PubMed 39807668Vernooij RW, Michael M, Ladhani M, Webster AC, Strippoli GF, Craig JC, Hodson EM. Antiviral medications for preventing cytomegalovirus disease in solid organ transplant recipients. Cochrane Database Syst Rev. 2024 May 3;5(5):CD003774. doi: 10.1002/14651858.CD003774.pub5.
PubMed 38700045
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00947141
- Acronym / sponsor ID
- 6077
- Conditions
- Viraemia
- Keywords
- Optimising treatment of cytomegalovirus infection
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 165 participants (actual)
- Lead sponsor
- University College, LondonUniversity, hospital or other
- Study start
- Feb 2003
- Primary completion
- Dec 2011 (actual)
- Study completion
- Feb 2013 (actual)
- First posted
- 27 Jul 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A | Experimental | Drug: ganciclovir (start when CMV PCR >200copies / ml x2), Other: Monitor (Treatment starts when CMV PCR >3,000 copies / ml)Group A: (low level infection) has 2 arms: 1. Start treatment when 2 consecutive levels CMV PCR >200copies / ml 2. Monitor (Treatment starts when CMV PCR >3,000 copies / ml (current site clinical protocol)) |
| Group B | Experimental | Drug: Stop treatment when 2 levels CMV PCR <3,000 copies / ml, Other: Monitor (Treatment stops CMV PCR <200 copies / ml x2)Group B: (patients receiving pre-emptive therapy) has 2 arms: 1. Stop treatment when 2 levels CMV PCR <3,000 copies / ml 2. Monitor (Treatment stops when there are 2 consecutive levels of CMV PCR <200 copies / ml (current site clinical protocol)) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ganciclovir (start when CMV PCR >200copies / ml x2)Also: valganciclovir, foscarnetGroup 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 | Drug | Group A |
| Monitor (Treatment starts when CMV PCR >3,000 copies / ml)Also: valganciclovir, foscarnetGroup 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 | Other | Group A |
| Stop treatment when 2 levels CMV PCR <3,000 copies / mlAlso: valganciclovir, foscarnetGroup 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 | Drug | Group B |
| Monitor (Treatment stops CMV PCR <200 copies / ml x2)Also: valganciclovir, foscarnetGroup 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 | Group B |
Primary outcome
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
1 secondary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2017.
- Derived from this study: PubMed 39807668Vernooij RW, Michael M, Colombijn JM, Owers DS, Webster AC, Strippoli GF, Hodson EM. Pre-emptive treatment for cytomegalovirus viraemia to prevent cytomegalovirus disease in solid organ transplant recipients. Cochrane Database Syst Rev. 2025 Jan 14;1(1):CD005133. doi: 10.1002/14651858.CD005133.pub4.
- Derived from this study: PubMed 38700045Vernooij RW, Michael M, Ladhani M, Webster AC, Strippoli GF, Craig JC, Hodson EM. Antiviral medications for preventing cytomegalovirus disease in solid organ transplant recipients. Cochrane Database Syst Rev. 2024 May 3;5(5):CD003774. doi: 10.1002/14651858.CD003774.pub5.
Related trials for Viraemia
RecruitingPhase 2
CMV-MVA Triplex Vaccination in HLA-Matched Related Stem Cell Donors for the Prevention of CMV Infection in Patients Undergoing Hematopoietic Stem Cell Transplant
Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia
RecruitingPhase 1
A Vaccine (CMV-MVA Triplex Vaccine) for the Enhancement of CMV-Specific Immunity and the Prevention of CMV Viremia in Patients Undergoing Haploidentical Hematopoietic Stem Cell Transplant
Accelerated Phase Chronic Myeloid Leukemia, BCR-ABL1 Positive, Acute Lymphoblastic Leukemia
RecruitingPhase 2
A Trial to Evaluate the Safety, Tolerability and Efficacy of AIC263029 in Kidney Transplant Recipients With BKV Infection
BK Virus Infection, BKV Infection
Not yet recruitingEarly Phase 1
25BT056: Basket Study of Viral Cytotoxic T Lymphocytes
EBV Viremia, CMV Viremia
Active, not recruiting
A Controlled Human Infection Model of Dengue
Dengue
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Professor Paul D Griffiths, MD DSc principal investigator
University College, London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing ganciclovir (start when CMV PCR >200copies / ml x2), Monitor (Treatment starts when CMV PCR >3,000 copies / ml) and Stop treatment when 2 levels CMV PCR <3,000 copies / ml in people with Viraemia, run by University College, London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00947141, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2017.