A Phase III Randomized Multicenter Clinical Trial Of High-Dose Human Albumin Therapy For Neuroprotection In Acute Ischemic Stroke
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 841
- 试验地点
- 89
- 主要终点
- The Number of Participants With Favorable Outcome Defined as National Institute of Health Stroke Scale (NIHSS) Score of 0-1 and/or Modified Rankin Scale (mRS) of 0-1.
研究概览
简要总结
The goal of the trial is to determine whether human albumin, administered within 5 hours of symptom onset, improves the 3-month outcome of subjects with acute ischemic stroke.
详细描述
Human serum albumin, at 2 g/kg, administered over 2 hours by intravenous infusion, will be compared to placebo (isovolumic normal saline) among patients with acute ischemic stroke. All patients will have a baseline stroke severity measured as NIH Stroke scale score > 5. Patients will treated according to the best standard of care including concurrent treatment with intravenous or intra-arterial thrombolysis where appropriate. The primary outcome will be determined at 3 months. The primary hypothesis is that, using the composite outcome of a modified Rankin score 0-1 or NIH stroke scale score 0-1 at 3 months (or both), the proportion of patients with improved outcomes will be greater by 10% or more in the active treatment group. [The current trial is termed "Part 2" and incorporates revisions to the initial protocol that were instituted after the Data Safety Monitoring Board (DSMB) suspended subject recruitment because of a safety concern after 434 subjects had been enrolled. The protocol revisions of Part 2 resulted from the study team's thorough review of the Part-1 safety data and were designed to optimize safety going forward.]
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, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 83 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Acute ischemic stroke
- •NIH stroke scale score > 5
- •Age >= 18 and <= 83
- •ALB or placebo can be administered within 5 hours of symptom onset
- •ALB or placebo can be administered within 60 minutes of Tissue Plasminogen Activator (tPA) administration in the thrombolysis group
- •Signed informed consent
排除标准
- •Episode/exacerbation of congestive heart failure (CHF) from any cause in the last 6 months. An episode of congestive heart failure is any heart failure that required a change in medication, diet or hospitalization.
- •Known valvular heart disease with CHF in the last 6 months.
- •Severe aortic stenosis or mitral stenosis.
- •Cardiac surgery involving thoracotomy (e.g., coronary artery bypass graft (CABG), valve replacement surgery) in the last 6 months.
- •Acute myocardial infarction in the last 6 months.
- •Signs or symptoms of acute myocardial infarction, including ECG findings, on admission.
- •Baseline elevated serum troponin level on admission (>0.1 mcg/L)
- •Suspicion of aortic dissection on admission.
- •Acute arrhythmia (including any tachycardia - or bradycardia) with hemodynamic instability.
- •Findings on physical examination of any of the following: (1) jugular venous distention (JVP > 4 cm above the sternal angle); (2) 3rd heart sound; (3) resting tachycardia (heart rate > 100/min) attributable to congestive heart failure; (4) abnormal hepatojugular reflux; (5) lower extremity pitting edema attributable to congestive heart failure; and/or (6) definite chest x-ray evidence of pulmonary edema.
- •Current acute or chronic lung disease requiring supplemental chronic or intermittent oxygen therapy.
- •Historical Modified Rankin Score (mRS) ≥
- •Patients who live in a nursing home or who are not fully independent for activities of daily living immediately prior to the stroke are not eligible for the trial.
- •In-patient stroke. I.e., patients with a stroke occurring as a complication of hospitalization for another condition, or as a complication of a procedure.
- •Planned acute use of intra-arterial (IA) tPA or acute endovascular intervention (e.g., stenting, angioplasty, thrombus retrieval device use) must conform to the following criteria: (1) begin within 5 hours of symptom onset, and (2) finish within 7 hours of symptom-onset.
- •Fever, defined as core body temperature > 37.5° C (99.5°F).
- •Serum creatinine > 2.0 mg/dL or 180 µmol/L.
- •Profound dehydration.
- •Evidence of intracranial hemorrhage (intracerebral hematoma (ICH), subarachnoid hemorrhage (SAH), epidural hemorrhage, acute or chronic subdural hematoma (SDH)) on the baseline CT or MRI scan.
- •History of allergy to albumin.
- •History of latex rubber allergy.
- •Severe chronic anemia with Hgb < 7.5 g/dL
- •Pregnancy, breastfeeding or positive pregnancy test. (Women of childbearing age must have a negative pregnancy test prior to ALB administration.)
- •Concurrent participation in any other therapeutic clinical trial.
- •Evidence of any other major life-threatening or serious medical condition that would prevent completion of 3-month follow-up, impair the assessment of outcome, or in which ALB therapy would be contraindicated or might cause harm to the subject.
研究组 & 干预措施
Albumin (ALB)
Albumin (human albumin, 25% solution, 2.0 g/kg), infused intravenously over a period of 2 hours
干预措施: Albumin (Biological)
Saline
Saline (isotonic solution), 8 ml/kg, infused intravenously over a 2-hour period
干预措施: Saline (Drug)
结局指标
主要结局
The Number of Participants With Favorable Outcome Defined as National Institute of Health Stroke Scale (NIHSS) Score of 0-1 and/or Modified Rankin Scale (mRS) of 0-1.
时间窗: at 3 months
The National Institutes of Health Stroke Scale (NIHSS) is a systematic assessment tool that provides a quantitative measure of stroke-related neurologic deficit. The scores range from 0 to 42 with a score of greater than 20 indicating severe neurologic deficit. The mRS ranges from 0-6 representing perfect health without symptoms to death. A score of 0 is no symptoms at all and a score of 1 is no significant disability. Able to carry out all usual duties and activities.
次要结局
- Number of Participants With a Composite Outcome of mRS 0-1 and/or NIHSS 0-1 and/or Decrease in NIHSS From Baseline by 10 or More Points(at 3 months)
- Number of Participants With a NIHSS of 0-1 at 24 Hours(at 24 hours)
- Number of Participants With a NIHSS 0-1 at 90 Days.(at 90 days)
- The Number of Participants With a Score on the mRS 0-1 at 90 Days.(at 90 days)
- The Number of Participants With a Score on the mRS of 0-2 at 90 Days.(at 90 days)
- Number of Participants With a Favorable Outcome Per Modified Rankin Scare (mRS)(90 days)
- Barthel Index (BI) 95-100(at 90 days)
- Number of Participants With an EuroQol (EQ-5D) Favorable Score < 0.78(at 90 days)
- Number of Participants With a Stroke Specific Quality of Life Scale (SSQOL) Score of >=3(at 90 days)
- Trailmaking A(at 90 days)
- Trailmaking B(at 90 days)
- Number of Participants With Neurological Deterioration Within 48 Hours(within 48 hours)
- Neurological Death Within 7 Days(within 7 days)
- Recurrent Ischemic Stroke Within 30 Days(within 30 days)
- Atrial Fibrillation Within 48 Hours(within 48 hours)
- Pulmonary Edema Within 48 Hours(within 48 hours)
- Shortness of Breath Within 48 Hours(within 48 hours)
- Symptomatic Intracerebral Hemorrhage (ICH) Within 24 Hours(within 24 hours)
- Asymptomatic ICH Within 24 Hours(within 24 hours)
- Death Within 30 Days(within 30 days)
- Death Within 90 Days(within 90 days)
研究者
Myron Ginsberg
Principal Investigator; Peritz Scheinberg Professor of Neurology
University of Miami