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Meta-Analysis
. 2013 Feb 28;2013(2):CD005133.
doi: 10.1002/14651858.CD005133.pub3.

Pre-emptive treatment for cytomegalovirus viraemia to prevent cytomegalovirus disease in solid organ transplant recipients

Daniel S Owers  1 , Angela C Webster, Giovanni F M Strippoli, Kathy Kable, Elisabeth M Hodson
Affiliations
Meta-Analysis

Pre-emptive treatment for cytomegalovirus viraemia to prevent cytomegalovirus disease in solid organ transplant recipients

Daniel S Owers et al. Cochrane Database Syst Rev. .

Update in

Abstract

Background: Cytomegalovirus (CMV) is a significant cause of morbidity and mortality in solid organ transplant recipients. Pre-emptive treatment of patients with CMV viraemia using antiviral agents has been suggested as an alternative to routine prophylaxis to prevent CMV disease. This is an update of a Cochrane review first published in 2005.

Objectives: This review was conducted to evaluate the efficacy of pre-emptive treatment with antiviral medications in preventing symptomatic CMV disease.

Search methods: For this update, we searched the Cochrane Renal Group's Specialised Register (to 16 January 2013) through contact with the Trials' Search Co-ordinator using search terms relevant to this review.

Selection criteria: We included randomised controlled trials (RCTs) of pre-emptive treatment compared with placebo, no specific treatment or with antiviral prophylaxis in solid organ transplant recipients.

Data collection and analysis: Four authors assessed the quality and extracted all data. Analyses used a random-effects model and results were expressed as risk ratio (RR) and 95% confidence intervals (CI).

Main results: We identified 15 eligible studies (1098 participants). Of these, six investigated pre-emptive treatment versus placebo or treatment of CMV when disease occurred (standard care), eight looked at pre-emptive treatment versus antiviral prophylaxis, and one reported on oral versus intravenous pre-emptive treatment.Assessment of risk of bias identified that the processes reported for sequence generation and allocation concealment were at low risk of bias in only five and three studies, respectively. All studies were considered to be at low risk of attrition bias, and seven studies were considered to be at low risk of bias for selective reporting. Only one study reported adequate blinding of participants and personnel; no study reported blinding of outcome assessment.Compared with placebo or standard care, pre-emptive treatment significantly reduced the risk of CMV disease (6 studies, 288 participants: RR 0.29, 95% CI 0.11 to 0.80) but not acute rejection (3 studies, 185 participants: RR 1.21, 95% CI 0.69 to 2.12) or all-cause mortality (3 studies, 176 participants: RR 1.23, 95% CI 0.35 to 4.30). Comparative studies of pre-emptive therapy versus prophylaxis showed no significant differences in preventing CMV disease between pre-emptive and prophylactic therapy (7 studies, 753 participants: RR 1.00, 95% CI 0.36 to 2.74) but there was significant heterogeneity (I² = 63%). Leucopenia was significantly less common with pre-emptive therapy compared with prophylaxis (6 studies, 729 participants: RR 0.42, 95% CI 0.20 to 0.90). Other adverse effects did not differ significantly or were not reported. There were no significant differences in the risks of all-cause mortality, graft loss, acute rejection and infections other than CMV.

Authors' conclusions: Few RCTs have evaluated the effects of pre-emptive therapy to prevent CMV disease. Pre-emptive therapy is effective compared with placebo or standard care. Despite the inclusion of five additional studies in this update, the efficacy of pre-emptive therapy compared with prophylaxis to prevent CMV disease remains unclear due to significant heterogeneity between studies. Additional head-to-head studies are required to determine the relative benefits and harms of pre-emptive therapy and prophylaxis to prevent CMV disease in solid organ transplant recipients.

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Conflict of interest statement

None known.

Figures

Figure 1
Figure 1
Combined search results for the original and updated reviews. Reasons for exclusions are provided in text
Figure 2
Figure 2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies
Figure 3
Figure 3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study
Analysis 1.1
Analysis 1.1
Comparison 1 Pre‐emptive medication for CMV viraemia versus placebo or standard care, Outcome 1 All symptomatic CMV disease.
Analysis 1.2
Analysis 1.2
Comparison 1 Pre‐emptive medication for CMV viraemia versus placebo or standard care, Outcome 2 CMV organ involvement.
Analysis 1.3
Analysis 1.3
Comparison 1 Pre‐emptive medication for CMV viraemia versus placebo or standard care, Outcome 3 CMV associated symptoms.
Analysis 1.4
Analysis 1.4
Comparison 1 Pre‐emptive medication for CMV viraemia versus placebo or standard care, Outcome 4 Acute rejection.
Analysis 1.5
Analysis 1.5
Comparison 1 Pre‐emptive medication for CMV viraemia versus placebo or standard care, Outcome 5 All‐cause mortality and graft loss.
Analysis 1.6
Analysis 1.6
Comparison 1 Pre‐emptive medication for CMV viraemia versus placebo or standard care, Outcome 6 Other infections.
Analysis 1.7
Analysis 1.7
Comparison 1 Pre‐emptive medication for CMV viraemia versus placebo or standard care, Outcome 7 Adverse effects.
Analysis 2.1
Analysis 2.1
Comparison 2 Pre‐emptive medication versus prophylaxis, Outcome 1 All symptomatic CMV disease.
Analysis 2.2
Analysis 2.2
Comparison 2 Pre‐emptive medication versus prophylaxis, Outcome 2 CMV infection.
Analysis 2.3
Analysis 2.3
Comparison 2 Pre‐emptive medication versus prophylaxis, Outcome 3 All‐cause mortality and graft loss.
Analysis 2.4
Analysis 2.4
Comparison 2 Pre‐emptive medication versus prophylaxis, Outcome 4 Acute rejection.
Analysis 2.5
Analysis 2.5
Comparison 2 Pre‐emptive medication versus prophylaxis, Outcome 5 Other infections.
Analysis 2.6
Analysis 2.6
Comparison 2 Pre‐emptive medication versus prophylaxis, Outcome 6 Adverse effects.
Analysis 2.7
Analysis 2.7
Comparison 2 Pre‐emptive medication versus prophylaxis, Outcome 7 D+/R‐ serostatus.
Analysis 2.8
Analysis 2.8
Comparison 2 Pre‐emptive medication versus prophylaxis, Outcome 8 D+ or D‐/R+ serostatus.
Analysis 3.1
Analysis 3.1
Comparison 3 Oral versus IV ganciclovir, Outcome 1 All symptomatic CMV disease.
Analysis 3.2
Analysis 3.2
Comparison 3 Oral versus IV ganciclovir, Outcome 2 All‐cause mortality.
Analysis 3.3
Analysis 3.3
Comparison 3 Oral versus IV ganciclovir, Outcome 3 Other infections.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

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References to studies excluded from this review

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References to studies awaiting assessment

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References to ongoing studies

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    1. Potena L, Grigioni F. Prevention of Transplant Atherosclerosis With Everolimus and Anti‐cytomegalovirus Therapy (PROTECT). http://clinicaltrials.gov/ct2/show/NCT00966836 (accessed 10 January 2013).
    1. Singh N. Prophylaxis Versus Preemptive Therapy for the Prevention of CMV in Liver Transplant Recipients (CAPSIL). http://clinicaltrials.gov/ct2/show/NCT01552369 (accessed 10 Janaury 2013).

Additional references

    1. Arthurs SK, Eid AJ, Pedersen RA, Dierkhising RA, Kremers WK, Patel R, et al. Delayed‐onset primary cytomegalovirus disease after liver transplantation. Liver Transplantation 2007;13(12):1703‐9. [MEDLINE: ] - PubMed
    1. Arthurs SK, Eid AJ, Pedersen RA, Kremers WK, Cosio FG, Patel R, et al. Delayed‐onset primary cytomegalovirus disease and the risk of allograft failure and mortality after kidney transplantation. Clinical Infectious Diseases 2008;46(6):840‐6. [MEDLINE: ] - PubMed
    1. British Transplantation Society. Guidelines for the prevention and management of cytomegalovirus disease after solid organ transplantation. 3rd Edition. London: British Transplantation Society, 2011. - PubMed
    1. Pillmore H. Pre‐emptive treatment of cytomegalovirus. http://www.cari.org.au/TRANS_cmv_published/Pre‐emptive_treatment_CMV_Oct... (accessed 10 January 2013).
    1. European Best Practice Guidelines Expert Group on Renal Transplantation. Section III: The transplant recipient from initial transplant hospitalization to 1 year post transplant. Nephrology Dialysis Transplantation 2000;15(Suppl 7):52‐85.

References to other published versions of this review

    1. Strippoli GF, Craig JC, Hodson EM, Jones C. Pre‐emptive treatment for cytomegalovirus viraemia to prevent cytomegalovirus disease in solid organ transplant recipients. Cochrane Database of Systematic Reviews 2005, Issue 1. [DOI: 10.1002/14651858.CD005133] - DOI - PubMed
    1. Strippoli GF, Hodson EM, Jones CA, Craig JC. Pre‐emptive treatment for cytomegalovirus viraemia to prevent cytomegalovirus disease in solid organ transplant recipients. Cochrane Database of Systematic Reviews 2006, Issue 1. [DOI: 10.1002/14651858.CD005133.pub2] - DOI - PubMed
    1. Strippoli GF, Hodson EM, Jones C, Craig JC. Preemptive treatment for cytomegalovirus viremia to prevent cytomegalovirus disease in solid organ transplant recipients. Transplantation 2006;81(2):139‐45. [MEDLINE: ] - PubMed

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