Anti-viral Prophylaxis for Prevention of Cytomegalovirus (CMV) Reactivation in Immunocompetent Patients in Critical Care
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 124
- 试验地点
- 1
- 主要终点
- Time to reactivation of cytomegalovirus (CMV) polymerase chain reaction (PCR) (defined as above the lower limit of sample assay).
研究概览
简要总结
The purpose of this study is to determine whether reactivation of latent cytomegalovirus infection in critically ill patients looked after in the intensive care unit can be successfully and safely prevented using antiviral agents. Comparison is made between standard care, and treatment with one of two different antiviral regimens: valaciclovir/aciclovir, which has a favourable side effect profile but requires high dosage to be effective, and valganciclovir/ganciclovir, which has more side effects, but has been demonstrated to be effective in low dosage.
The primary hypothesis is that cytomegalovirus reactivation can be effectively suppressed with antiviral prophylaxis.
详细描述
Background:
* Cytomegalovirus (CMV) is a common virus which infects around half the UK population. Infection is usually mild, but after infection the virus is never completely eradicated, and may reactivate in ill health. Reactivation is most commonly seen in those with compromised immune systems, such as people with advanced HIV infection, or whilst on immunosuppression following organ transplantation. CMV reactivation in these patients can be life threatening. There is evidence to support the use of antiviral medication in these groups of immunosuppressed patients to prevent CMV reactivation, and their use is part of standard therapy. There is increasing evidence demonstrating that a third of critically ill patients will reactivate CMV, and these patients have as much as a doubled mortality.
Aims:
* This study is a proof of concept study designed to assess whether antiviral prophylaxis can effectively and safely suppress CMV reactivation in CMV seropositive high risk critically ill patients. Antiviral prophylaxis is currently not standard practice in critical care units, and no previous trials of prophylaxis have been undertaken in this setting. All commonly used antiviral agents have side effects, and it is important to demonstrate their efficacy and safety in the critical care setting before undertaking a large multicentre trial powered to identify mortality or morbidity differences with prophylaxis. Intravenous ganciclovir, and its oral prodrug valganciclovir have been effectively used as prophylaxis at low doses in immunosuppressed patients. Intravenous aciclovir and its oral prodrug valaciclovir in high dosage have also been demonstrated to be effective as prophylaxis in immunosuppressed patients. This study sets out to determine whether their use in critically ill patients are both effective and safe.
Plan of Investigation:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Total hospital stay of less than 7 days
- •CMV seropositive
- •Critical care stay of >24 hours
- •Mechanically ventilated, anticipated to continue for > 48 hours
排除标准
- •Known Pregnancy or breast feeding
- •Expected to survive less than 48 hours
- •Confirmed immunosuppression
- •Known or suspected Human Immunodeficiency Virus infection
- •Known or suspected underlying immunodeficiency (organ transplantation including stem cell transplantation on immunosuppression, congenital immunodeficiency, in receipt of immunosuppressive medication e.g. azathioprine, methotrexate, tacrolimus, cyclosporine, sirolimus, cyclophosphamide within 30 days)
- •Corticosteroids: Prednisolone chronic administration may be used up to a dose of 10mg/day on average over the preceding 30 days, stress dose hydrocortisone (up to 400mg/day) may be used, topical steroids may be used, short duration of higher dose steroids for exacerbations of chronic obstructive pulmonary disease (COPD) up to 1mg/kg prednisolone or equivalent are permitted for up to 14 days
- •Receipt of chemotherapeutic agent within the last 6 months
- •Use of systemic antiviral medication other than oseltamivir within the last 7 days.
- •Intubated and mechanically ventilated secondary to brain injury alone.
研究组 & 干预措施
Valaciclovir/Aciclovir
干预措施: Valaciclovir/Aciclovir (Drug)
Valganciclovir/Ganciclovir
干预措施: Valganciclovir/Ganciclovir (Drug)
结局指标
主要结局
Time to reactivation of cytomegalovirus (CMV) polymerase chain reaction (PCR) (defined as above the lower limit of sample assay).
时间窗: 28 days
In the event of patient discharge from hospital or death, the results will be censored at the most proximate blood CMV PCR sample point.
次要结局
- Time to reactivation above the lower limit of assay detection of CMV PCR in urine, throat swab and non-directed bronchiolar lavage (NDBL). NDBL whilst trachea is intubated only.(28 days)
- Time to >1000 CMV copies in blood, urine, throat swab and NDBL (NDBL whilst intubated)(28 days)
- Time to neutropenia (count <1.0x10-9/L)(28 days)
- Time to thrombocytopenia (platelet <50x10-9/L)(28 days)
- Use of G-CSF or termination of study drug(28 days)
- Number of platelet transfusions received(28 days)
- Time to renal insufficiency (CrCl <60ml/min, <30ml/min, need for renal support)(28 days)
- Time to >10000 CMV copies in blood, urine, throat swab and NDBL (NDBL whilst intubated)(28 days)
- CMV PCR in blood, urine, throat swab and NDBL (NDBL whilst intubated)(28 days)
- Markers of inflammation(28 days)
- Clinical Outcomes(from randomization to hospital discharge (up to 3 months))
- Number of Serious Adverse events(28 days)
研究者
Julian F Bion
Professor of Intensive Care Medicine
University Hospital Birmingham NHS Foundation Trust