Breakthrough CMV DNAemia in CMV Seronegative Recipients of CMV Seropositive Lung Transplantation During Antiviral Prophylaxis With Valganciclovir. A Pilot Study.
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- CMV Breakthrough
研究概览
简要总结
Cytomegalovirus (CMV) infection is the most common opportunistic infection in lung transplantation leading to direct and indirect effects that can result in life threatening complications. The risk of CMV infection is highest when the recipient of the transplant has never been in contact with CMV (negative immunity) and the donor had previous contact with CMV (positive immunity). This is called CMV mismatch. For these lung transplant patients 6 to 12 months of prophylaxis with an antiviral called Valganciclovir is recommended. This antiviral can cause side effects like bone marrow toxicity and decrease in immune cells which can result in temporarily having to stop the treatment. Starting and stopping the prophylaxis may result in the CMV becoming resistant to the medication. While taking the prophylaxis it is possible to have a breakthrough of the CMV, this is often due to the development of resistance to the antiviral. The purpose of this study is to learn more about the rate of CMV breakthrough while on prophylaxis after lung transplantation in patients who are CMV mismatch. The investigators will also look at the rates of negative side effects caused by antiviral prophylaxis in this population.
详细描述
Purpose:
The purpose of this study is to learn more about the rate of CMV breakthrough in lung transplant patients who are CMV mismatched and receiving prophylaxis. The rates of negative side effects caused by the antiviral prophylaxis will also be monitored. For patients who do have a breakthrough of CMV viremia while on study the investigator will also evaluate the rate of resistance mutations.
Hypothesis:
The investigator wants to demonstrate that breakthrough CMV DNAemia is common in CMV mismatch lung transplant recipients on ganciclovir/valganciclovir prophylaxis. In addition, the investigator will show that leukopenia and neutropenia related to prolonged prophylaxis is very common and discontinuation of ganciclovir/valganciclovir prophylaxis because of side effects explains most cases of breakthrough CMV DNAemia. The investigators findings will be relevant because they will answer the following questions:
- Prophylaxis with ganciclovir/valganciclovir in mismatch lung transplant patients should include intensive CMV DNA monitoring.
- Side effects related to the use of ganciclovir/valganciclovir can result in potential life-threatening infections due to the development of neutropenia and increased cost due to the use of granulocyte-colony stimulating factor.
- Alternative prophylaxis with new antivirals with safer profile of side effects would result in a safer profile of adverse events. As resistance to ganciclovir may lead to death, the development of CMV infection in patients receiving antivirals targeting different enzymes than those targeted by ganciclovir/valganciclovir will not prevent future use of ganciclovir/valganciclovir to treat CMV infection or disease.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
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
- •CMV seronegative recipients of CMV seropositive donor lung transplantation.
- •Age 18 years or older.
- •Receipt of antiviral prophylaxis with valganciclovir as per local protocol with a duration of 6 or 12 months after transplantation.
- •Monitoring of CMV DNAemia post-prophylaxis for at least 12 weeks as per local protocol.
- •Signed informed consent.
排除标准
- •Known allergy to ganciclovir or valganciclovir.
- •Neutropenia (< 1.0) pre-transplantation.
- •Living-donor lung transplantation.
- •Lung re-transplantation.
- •Pre-transplant immunodeficiency
结局指标
主要结局
CMV Breakthrough
时间窗: Up to 52 weeks
Incidence of CMV infection (defined as any quantifiable CMV viral load in plasma or blood) during prophylaxis. Will be categorized as CMV asymptomatic infection or CMV disease.
次要结局
- Death(through study completion, up to 64 weeks)
- CMV infection(12 weeks)
- Leukopenia(through study completion, up to 64 weeks)
- Opportunistic and non-opportunistic infections(through study completion, up to 64 weeks)
- Chronic lung allograft dysfunction(through study completion, up to 64 weeks)
- Retransplantation(through study completion, up to 64 weeks)
- Neutropenia(through study completion, up to 64 weeks)
- Severe neutropenia(through study completion, up to 64 weeks)
- CMV resistant infection(through study completion, up to 64 weeks)
- Use of Granulocyte - colony stimulating factor (G-CSF)(through study completion up, to 64 weeks)