E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To ascertain whether high-dose human albumin (ALB) therapy confers neuroprotection in acute ischemic stroke over and above best standard of care. (Specifically, to determine whether ALB therapy increases the proportion of acute ischemic stroke patients with favorable outcome compared to placebo therapy at 3 months from randomization, as measured by the NIHSS and mRS.) |
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E.2.2 | Secondary objectives of the trial |
To evaluate: - overall clinical outcome (as assessed by the global statistical test of NIHSS, mRS, and BI scores) at 3 months post-randomization, - overall clinical outcome as assessed by the full scale of the modified Rankin scale, - neurological outcome as assessed by NIHSS score at 3 months post-randomization, - functional outcome as assessed by mRS and BI at 3 months post-randomization, - quality-of-life as assessed by EuroQol at 3 months and 1 year post-randomization, and by SSQOL instruments at 3 months post-randomization, - robustness of ALB therapy as measured by a favorable outcome of mRS of 0 or 1at one year post-randomization, - incidence of recurrent ischemic stroke within 1 month, 3 months and 1 year post-randomization, as assessed by QVSFS, - mortality within 3 months and 1 year post-randomization, - incidence of symptomatic ICH within 24 (± 6) hours of randomization, - cognition measured at 3 months by Trailmaking A and B.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Acute ischemic stroke
- Age 18 years through 83 years (have not had their 84th birthday).
- NIHSS score of 6 or greater as assessed immediately prior to intravenous thrombolysis treatment if the patient is eligible for intravenous thrombolysis or immediately prior to randomization for patients not eligible for intravenous thrombolysis.
- Initiation of ALB/placebo within 5 hours of stroke onset, and within 90 minutes of the start of thrombolysis with intravenous (IV) tPA if that therapy is used. Signed and dated informed consent has been obtained.
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E.4 | Principal exclusion criteria |
- Episode/exacerbation of congestive heart failure (CHF) from any cause in the last 6 months.
- Known valvular heart disease with CHF in the last 6 months.
- Known (or in the Investigator’s clinical judgment) existence of severe aortic stenosis or mitral stenosis.
- Cardiac surgery involving thoracotomy in the last 6 months.
- Acute myocardial infarction in the last 6 months.
- Signs or symptoms of acute myocardial infarction, including EKG findings, on admission.
- Elevated serum troponin level on admission (> 0.1 mcg/L)
- Suspicion of aortic dissection on admission.
- Acute arrhythmia with hemodynamic instability on admission
- Findings on physical examination of any of the following: (1) jugular venous distention; (2) 3rd heart sound; (3) resting tachycardia attributable to congestive heart failure; (4) lower extremity pitting edema attributable to congestive heart failure; abnormal hepatojugular reflux; (5) bilateral rales; and/or (6) if a chest x-ray is performed, definite evidence of pulmonary edema, bilateral pleural effusion, or pulmonary vascular redistribution
- Current acute or chronic lung disease requiring supplemental chronic or intermittent oxygen therapy.
- Historical modified Rankin Scale (mRS) >2. 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. Patients with stroke occurring as a complication of hospitalization for another condition, or as a complication of a procedure.
- Profound dehydration.
- Fever, defined as core body temperature > 38.0oC
- Serum creatinine > 2.0 mg/dL or 180 mol/L
- Severe chronic anemia (hemoglobin < 7.5 g/dL or 75g/L).
- Evidence of intracranial hemorrhage (intracerebral hematoma, intraventricular hemorrhage, subarachnoid hemorrhage (SAH), epidural hemorrhage, acute or chronic subdural hematoma (SDH)) on the baseline CT or MRI scan.
- History of or known allergy to albumin.
- History of or known allergy to natural rubber latex.
- Pregnancy, breastfeeding or positive pregnancy test.
- Concurrent participation in any other therapeutic clinical trial.
- Evidence of any other major life-threatening or serious medical condition that would prevent completion of the study protocol, impair the assessment of outcome, or in which ALB therapy would be contraindicated or might cause harm to the subject.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome is the favorable outcome, defined as either NIH Stroke Scale (NIHSS) score of 0 or 1, or a modified Rankin Score (mRS) of 0 or 1, or both, measured at 3 months from randomization. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
3 months from randomization |
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E.5.2 | Secondary end point(s) |
Secondatory end points are measured, as specified, out to 12 months from randomization. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
Finland |
Israel |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Patients are followed up to 12 month after randomization |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |