A Randomized Double-Blind, Phase 3 Study Comparing the Efficacy and Safety of High-Titer Versus Low-Titer Anti-Influenza Immune Plasma for the Treatment of Severe Influenza A
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 138
- 试验地点
- 30
- 主要终点
- Clinical Status at Day 7
研究概览
简要总结
This study assessed the efficacy and safety of anti-influenza immune plasma, as an addition to standard of care antivirals, in participants hospitalized with severe influenza A infection.
详细描述
Despite antivirals and vaccines, influenza is responsible for thousands of hospitalizations and deaths each year worldwide. Because of this, additional treatments for influenza are needed. One potential treatment may be the use of high-titer anti-influenza immune plasma. The purpose of this study is to evaluate the efficacy and safety of treatment with high-titer versus low-titer anti-influenza immune plasma, in addition to standard care, in participants hospitalized with severe influenza A infection.
This study enrolled people aged 2 weeks or older who are hospitalized with severe influenza A infection. Participants were randomly assigned to receive either high-titer anti-influenza plasma or low-titer (control) anti-influenza plasma on Day 0. In addition, all participants received standard care antivirals. Participants were assessed on Day 0 (baseline) and on Days 1, 2, 3, 7, 14, and 28. For participants who were not hospitalized on Days 2, 14, and 28, researchers could contact participants by telephone. Study procedures included clinical assessments, blood collection, and oropharyngeal swabs.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 2 Weeks 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •for Enrollment (Screening):
- •Subjects must be aged 2 weeks or older.
- •Hospitalization due to signs and symptoms of influenza.
- •* Note: The decision for hospitalization will be made by the treating clinician. To be considered eligible, the hospitalization may either be an initial hospitalization, or a prolongation of a hospitalization due to a respiratory illness that was found to be from influenza. Influenza could be a component of a larger respiratory syndrome (i.e. COPD exacerbation thought to be triggered by influenza). However, respiratory syndromes that are not likely due to the virus should not be included (i.e. a subject that had mild influenza then developed pulmonary embolism and respiratory distress from the embolism).
- •Study plasma available on-site or available within 24 hours after randomization.
- •Not previously screened nor randomized in this study.
- •Willingness to have blood and respiratory samples obtained and stored.
- •Willingness to return for all required study visits and participate in study follow up.
- •Inclusion Criteria for Randomization:
- •Locally determined positive test for influenza A (by polymerase chain reaction [PCR], other nucleic acid testing, or by rapid Ag) from a specimen obtained less than or equal to 48 hours prior to randomization.
- •Onset of illness less than or equal to 6 days before randomization, defined as when the subject first experienced at least one respiratory symptom or fever.
- •Note: For subjects with chronic respiratory symptoms (chronic cough, or COPD with baseline dyspnea), the onset of symptoms is defined as the point when the symptoms changed during this illness). Hospitalized due to influenza, with anticipated hospitalization for more than 24 hours after randomization. Criteria for hospitalization will be up to the individual treating clinician.
- •National Early Warning (NEW) or Pediatric Early Warning (PEW) score greater than or equal to 3 within 12 hours prior to randomization.
- •ABO-compatible plasma available on-site or available within 24 hours after randomization.
排除标准
- •for Randomization:
- •Strong clinical evidence in the judgment of the site investigator that the etiology of illness is primarily bacterial super-infection in origin. Co-infection would be allowed, as there may be benefit to resolving influenza illness faster. Super-infection, where influenza illness occurred and is resolving, and new bacterial illness causing deterioration should be excluded (e.g., if the subject's respiratory infection is thought unlikely to benefit from additional antiviral therapy, this exclusion criteria would be met).
- •Prior treatment with any anti-influenza investigational drug, anti-influenza investigational intravenous immune globulin (IVIG), or anti-influenza investigational plasma therapy within 30 days prior to screening. Other investigational drug therapies (non-influenza) and administration of plasma and/or IVIG for non-influenza reasons are allowed.
- •History of allergic reaction to blood or plasma products (as judged by the site investigator).
- •A pre-existing condition or use of a medication that, in the opinion of the site investigator, may place the individual at a substantially increased risk of thrombosis (e.g., cryoglobulinemia, severe refractory hypertriglyceridemia, or clinically significant monoclonal gammopathy). Prior IVIG use alone would not meet exclusion criteria, but the investigator should consider the potential for a hyper-coagulable state.
- •Subjects who, in the judgment of the site investigator, will be unlikely to comply with the requirements of this protocol, including being not contactable following discharge from hospital.
- •Medical conditions for which receipt of 500-600 mL (or pediatric equivalent) of intravenous fluid may be dangerous to the subject (e.g., decompensated congestive heart failure).
研究组 & 干预措施
High-titer anti-influenza plasma
Participants received two intravenous infusions of high-titer anti-influenza plasma on Study Day 0.
干预措施: High-titer anti-influenza plasma (Biological)
Low-titer anti-influenza plasma
Participants received two intravenous infusions of low-titer anti-influenza plasma on Study Day 0.
干预措施: Low-titer anti-influenza plasma (Biological)
结局指标
主要结局
Clinical Status at Day 7
时间窗: Day 7
The clinical status at Day 7 was based on a 6-point ordinal scale: 1. Death 2. In ICU 3. Non-ICU hospitalization, requiring supplemental oxygen (O2) 4. Non-ICU hospitalization, not requiring supplemental oxygen 5. Not hospitalized, but unable to resume normal activities 6. Not hospitalized with full resumption of normal activities A higher score corresponds to a better health outcome
次要结局
- 28-day Mortality(From Day 0 to Day 28)
- Change From Baseline to Day 3 and Day 7 in Pediatric Early Warning (PEW) Score(Day 0, Day 3, Day 7)
- Duration of Supplemental Oxygen(From Day 0 to Day 28 visit. The window of the Day 28 visit was 28-32 days from study entry.)
- Duration of Initial Hospitalization(From Day 0 to Day 28)
- Duration of Mechanical Ventilation Use(From Day 0 to Day 28 visit. The window of the Day 28 visit was 28-32 days from study entry)
- Incidence of New ECMO Use During the Study(From Day 0 to Day 28)
- Change From Baseline to Day 3 and Day 7 in Pediatric Logistic Organ Dysfunction (PELOD) Score(Day 0, Day 3, Day 7)
- Hemagglutination Inhibition Assay (HAI) Titers at Days 1, 3, 7 for A/H1N1(Day 1, Day 3, Day 7)
- Clinical Status at Day 1(Day 1)
- Clinical Status at Day 2(Day 2)
- Clinical Status at Day 3(Day 3)
- Change From Baseline to Day 3 and Day 7 in National Early Warning (NEW) Score(Day 0, Day 3, Day 7)
- Incidence of New Oxygen Use During the Study(From Day 0 to Day 28)
- In-hospital Mortality During Initial Hospitalization(From Day 0 to Day 28)
- Clinical Status at Day 28(Day 28)
- Composite of Mortality and Hospitalization at Day 7, Day 14, Day 28(Day 7, Day 14, Day 28)
- Duration of Intensive Care Unit (ICU) Stay(From Day 0 to Day 28)
- Incidence of New ARDS During the Study(From Day 0 to Day 28)
- Number of Participants With Serious Adverse Events (SAEs).(From Day 0 to Day 28)
- Duration of Extracorporeal Membrane Oxygenation (ECMO)(From Day 0 to Day 28)
- Disposition After Initial Hospitalization(From Day 0 to Day 28)
- Incidence of New ICU Admission Use During the Study(From Day 0 to Day 28)
- Incidence of New Mechanical Ventilation Use Stay Use During the Study(From Day 0 to Day 28)
- Duration of Acute Respiratory Distress Syndrome (ARDS)(From Day 0 to Day 28)
- Change From Baseline to Day 3 and Day 7 in Sequential Organ Failure Assessment (SOFA) Score(Day 0, Day 3, Day 7)
- Hemagglutination Inhibition Assay (HAI) Titers at Days 1, 3, 7 for A/HongKong/4801/2014 H3N2(Day 1, Day 3, Day 7)
- Number of Participants With Grade 3 and 4 Adverse Events (AEs).(From Day 0 to Day 28)
- Detectable Influenza Virus at Day 3(Day 3)
- Clinical Status at Day 14(Day 14)