Effect of Acyclovir Therapy on the Outcome of Ventilated Patients With Lower Respiratory Tract Infection and Detection of Herpes Simplex Virus in Bronchoalveolar Lavage
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 616
- 试验地点
- 48
- 主要终点
- mortality (survival status)
研究概览
简要总结
Almost 90 out of 100 people carry herpes simplex viruses (HSV). Once a person has been infected with the herpes viruses, he or she can't get rid of them for the rest of her/his life. For the most part, the viruses are in a dormant state. Only when the immune system is weakened, for example in the case of a serious illness or stress, are the viruses reactivated. They then mainly cause cold sores, which are harmless for healthy people and usually heal without therapy. However, especially in people with a weakened immune system, HSV can also cause serious infections, such as meningitis. In almost every second mechanically ventilated patient in intensive care who has pneumonia, HSV can be detected in the respiratory tract. This is caused by reactivation of the viruses as a result of the severe underlying disease and stress during intensive care therapy. Whether treatment of the herpes viruses (e.g. with acyclovir) is necessary in this situation and helps the patients to cure has not been clarified, especially as acyclovir can also cause side effects such as a deterioration in kidney function. Currently, the physicians decide to treat the herpes viruses in about half of the patients. Several studies have shown that patients for whom the physician decided to treat the viruses survived more often. However, all of these studies looked at the course of the disease only retrospectively and thus are subject to many biases (including physician selection of who receives treatment, missing data). A definitive conclusion as to whether herpesvirus therapy can be recommended cannot be drawn without doubt from these studies. Therefore, the investigators would like to investigate in a randomized controlled trial, i.e. patients are randomly assigned to the experimental (therapy of herpesviruses) or control group (no therapy of herpesviruses), the effect of therapy with acyclovir on survival in ventilated intensive care patients with lower respiratory tract infection (pneumonia) in whom a large amount of HSV was found in the respiratory tract. The goal of the study is to provide clarity on whether therapy will help patients recover.
详细描述
Herpes-simplex virus (HSV) can be detected in the bronchoalveolar lavage (BAL) in up to 60% of mechanically ventilated (MV) ICU patients with a lower respiratory tract infection (LRTI), depending on the study population and the severity of disease. However, it remains unclear whether the detection represents a harmless viral shedding as a consequence of reactivation, reflecting the severity of the underlying disease and immunoparalysis, or a true clinical infection requiring antiviral therapy. To date, only retrospective studies have investigated the benefit of an antiviral therapy in HSV-positive ICU patients on mechanical ventilation (MV) with LRTI. In a retrospective study and additional meta-analysis on this topic a antiviral treatment was associated with an improved patient outcome, i.e.; lower all-cause hospital mortality (RR 0.74, 95% CI 0.64-0.85) and lower 30-day all-cause mortality (RR 0.75, 95% CI 0.59-0.94; 3 studies). Aim of this study is to determine prospectively in a multicenter, randomized controlled trial whether acyclovir therapy improves outcome in ventilated ICU patients with a LRTI and HSV detection in BAL. Overall, 616 ICU patients with MV and LRTI and HSV1-PCR-detection in BAL (>= 10E3 copies/ml) will be either randomized to receive acyclovir (10mg/kg body weight tid) for 10 days (or discharge from ICU if this is earlier) or no antiviral therapy (control group). Primary efficacy endpoint will be overall survival within 30 days comparing the acyclovir therapy and the control group. Secondary endpoints include ventilation-free days up to day 30, vasopressor-free days until day 30 and safety.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 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
- •need for invasive or non-invasive respiratory support
- •PCR HSV-1 detection in BAL (≥ 10^3 copies/ml)
- •Pneumonia (community or healthcare acquired, incl. ventilator-associated pneumonia)
- •declaration of consent by the patient or legal representative
排除标准
- •History of hypersensitivity to acyclovir or valacyclovir or other components of the investigational product.
- •Pregnancy/Lactation 3.
- •Simultaneous participation in another clinical interventional trial under EU Regulation 536/2014, the German Medicines Act (AMG), Medical Devices Regulation (MDR), or Medical Devices Act (MPDG) without prior consultation and approval by the respective sponsors prior to randomization
- •4.Decision to withhold life-sustaining therapies 5.Use of a virostatic agent (i.v. or p. os) with activity against herpes simplex (acyclovir, valacyclovir, famciclovir/penciclovir, brivudine, cidofovir, foscarnet) for therapeutic or prophylactic reasons at the time of randomization.
- •6.Solid organ transplantation, stem cell transplantation 7.Neutropenia (absolute neutrophil count <1500/μl (<1.5 × 109 /l) 8.Previous study participation in HerpMV
研究组 & 干预措施
Treatment group
Aciclovir therapy
干预措施: Acyclovir (Drug)
结局指标
主要结局
mortality (survival status)
时间窗: day 30
survival status
次要结局
- Length of stay in Hospital(day 30)
- Cost of intervention(up to day 90)
- Ventilation-free days(day 30)
- Vasopressor-free days(day 30)
- Days without delirium/coma(Until day 10 or until EOT if this event occurs earlier)
- mortality (survival status)(180 days)
- Delta SOFA score (Sepsis-related Organ Failure Assessment Score)(Baseline - Day 10 or EOT if this event occurs earlier)
- Delta SOFA sub-score kidney (Sepsis-related Organ Failure Assessment Score)(Baseline - Day 10 or EOT if this event occurs earlier)
- Delta GFR value(Baseline - Day 10 or EOT if this event occurs earlier)
- Length of stay in ICU(day 30)
- Incidence SAEs(From time of randomization until day 10 or EOT if this event occurs earlier)
- Microbiological cure (EOT)(At day 10 or day of EOT if this event occurs earlier)
- Quality of life (EQ-5D-5L)(Measurement at day 10 or EOT if this event occurs earlier, day 30, day 90, and day 180)
- mortality (survival status)(90 days)
研究者
Stefan Hagel
Principal Investigator
Jena University Hospital