NCT04706507终止3 期
Ganciclovir to Prevent Reactivation of Cytomegalovirus in Patients With Acute Respiratory Failure and Sepsis
适应症
干预措施
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 205
- 试验地点
- 20
- 主要终点
- Respiratory-support-free Days in Immunocompetent Patients With Sepsis-associated Acute Respiratory Failure
研究概览
简要总结
This is a phase 3 study designed to evaluate whether the administration of ganciclovir increases ventilator-free days in immunocompetent patients with sepsis associated acute respiratory failure. Our hypothesis is that IV ganciclovir administered early in critical illness will effectively suppress CMV reactivation in CMV seropositive adults with sepsis-associated acute respiratory failure thereby leading to improved clinical outcomes
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject/next of kin informed consent
- •Age > 18 years
- •CMV IgG seropositive by lateral flow assay (LFA) or standard serologic methods
- •Receiving care in an ICU
- •Acute respiratory failure as defined in Section 4.1.
- •Expected to require respiratory support for at least 2 more days after randomization
- •Infection confirmed or suspected by the treating clinician and felt to be the source of acute respiratory failure (Respiratory failure associated with infection confers at least 2 SOFA points above assumed baseline SOFA score of 0, thereby meeting Sepsis-3 definition).
排除标准
- •Known or suspected immunosuppression, including:
- •HIV+ (i.e. prior positive test or clinical signs of suspicion of HIV/AIDS; a negative HIV test is not required for enrollment)
- •stem cell transplantation:
- •within 6 months after autologous transplantation or
- •within 1 years after allogeneic transplantation (regardless of immunosuppression)
- •greater than 1 year of allogeneic transplantation if still taking systemic immunosuppression or prophylactic antibiotics (e.g. for chronic graft versus host disease) Note: if details of stem cell transplantation are unknown, patients who do not take systemic immunosuppression and do not take anti-infective prophylaxis are acceptable for enrollment and randomization.
- •solid organ transplantation with receipt of systemic immunosuppression (any time)
- •cytotoxic anti-cancer chemotherapy within the past three months (Note: next-of-kin estimate is acceptable)
- •congenital immunodeficiency requiring antimicrobial prophylaxis (e.g. TMP-SMX, dapsone, antifungal drugs, intravenous immunoglobulin)
- •receipt of one or more of the following in the indicated time period (see Appendix C):
- •within 6 months: alemtuzumab, antithymocyte/antilymphocyte antibodies, or other immunosuppressive drugs associated with CMV reactivation Note: if no information on these agents is available in the history and no direct or indirect evidence exists from the history that any condition exists that requires treatment with these agents (based on the investigator's assessment), the subject may be enrolled. For all drug information, next-of-kin estimates are acceptable. See Appendix C for commonly prescribed immunosuppressive agents. Information on the use of biologics with moderate immunosuppressive effect but no known effect on CMV are permitted and will be recorded in the CRFs.
- •Expected to survive < 72 hours (in the opinion of the investigator)
- •Has been hospitalized for > 120 hours (subjects who are transferred from a chronic care ward, such as a rehabilitation unit, with an acute event are acceptable).
- •Pregnant or breastfeeding (either currently or expected within one month). Note: for women of childbearing age (18-60 years, unless documentation of surgical sterilization [hysterectomy, tubal ligation, oophorectomy]), if a pregnancy test has not been done as part of initial ICU admission work-up, it will be ordered stat and documented to be negative before randomization. Both urine and blood tests are acceptable.
- •Absolute neutrophil count < 1,000/mm3 (if no ANC value is available, the WBC must be > 2500/mm3)
- •Use of anti-CMV drugs (cidofovir, letermovir, foscarnet, valganciclovir, ganciclovir) within seven (7) days of patient randomization.
- •Currently enrolled in an interventional trial of an investigational therapeutic agent known or suspected to have anti-CMV activity or to be associated with significant known hematologic toxicity (prior approval required).
- •At baseline patients who have both a tracheostomy, and have been on continuous 24-hour chronic mechanical ventilation.
- •Patients with Child Class C Cirrhosis.
- •Patients with severe (requiring home oxygen) pre-existing interstitial lung disease.
- •Allergy to ganciclovir
- •Incarcerated
研究组 & 干预措施
IV Ganciclovir
Experimental
5mg/kg IV twice daily for 5 days, then followed by IV ganciclovir once daily until hospital discharge
干预措施: IV Ganciclovir (Drug)
Placebo
Placebo Comparator
normal saline IV twice daily for 5 days, then followed by IV normal saline once daily until hospital discharge
干预措施: Normal saline (Drug)
结局指标
主要结局
Respiratory-support-free Days in Immunocompetent Patients With Sepsis-associated Acute Respiratory Failure
时间窗: up to 28 days
To evaluate whether administration of ganciclovir increases respiratory-support-free days in immunocompetent patients with sepsis-associated acute respiratory failure. The outcome is the number of days the participant is not on respiratory support in the first 28 study days. This outcome uses the last-off approach to calculate the number of respiratory support days. The number of support days after calculated from the last day the participant was on respiratory support.
次要结局
- To Evaluate Whether Administration of Ganciclovir Increases Ventilator-free Days in Immunocompetent Patients With Sepsis-associated Acute Respiratory Failure.(up to 28 study days)
- To Evaluate Whether Administration of Ganciclovir Increases Total Respiratory-support-free Days (All RSFDS, Instead of Last-off Approach) in Immunocompetent Patients With Sepsis- Associated Acute Respiratory Failure(up to 28 days)
- To Evaluate Whether Mortality and Time to Death in the 28 Days is Different Among Ganciclovir Recipients Relative to Placebo Recipients, Respectively.(at study day 28)
- To Evaluate Whether Mortality and Time to Death in the 180 Days is Different Among Ganciclovir Recipients Relative to Placebo Recipients, Respectively.(at the final study visit (day 180))
- To Evaluate Whether Duration of Mechanical Ventilation Among Survivors in the First 28 Days is Different Among Ganciclovir Recipients Relative to Placebo Recipients.(up to 28 days)
- To Evaluate Whether Duration of Respiratory Support Among Survivors in the First 28 Days is Different Among Ganciclovir Recipients Relative to Placebo Recipients.(up to 28 days)
- To Evaluate Whether Oxygenation is Different Among Ganciclovir Recipients Relative to Placebo Recipients.(up to 7 days)
- To Evaluate Whether ICU-free Days in the First 28 Days Are Different Among Ganciclovir Recipients Relative to Placebo Recipients.(up to 28 days)
- To Evaluate Whether CMV DNA Detection in Plasma and Endotracheal Aspirate (ETA) by Day 28 is Different Among Ganciclovir Recipients Relative to Placebo Recipients.(up to 28 days)
- To Assess the Number and Severity of Adverse Events and Serious Adverse Events in the First 28 Days in Both Groups.(up to 28 days)
研究者
Michael Boeckh
Professor, Vaccine and Infectious Disease Division, Fred Hutch
Fred Hutchinson Cancer Center
研究点 (20)
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