E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute ischemic brain stroke |
Ictus isquémico agudo |
|
E.1.1.1 | Medical condition in easily understood language |
Acute cerebral infarction |
Infarto cerebral agudo |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
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 investigate in a pilot study the safety and efficacy of common diagnostic sulfur hexafluorid MBs on the beginning, degree, and time to maximum completeness of middle cerebral artery (MCA) recanalization during systemic thrombolysis and continuous 2-Hz pulsed-wave TCD monitoring. |
Evaluar la seguridad y eficacia del tratamiento con sonotrombolisis potenciado con MB en pacientes con infarto cerebral agudo |
|
E.2.2 | Secondary objectives of the trial |
1 To investigate whether the administration of ST plus MB treatment leads to an increase in the proportion of patients with MCA ischemic stroke that achieve an early clinical improvement (decrease in 4 or more points at at 24 h NIHSS) and good long-term functional outcome (Modified Rankin Scale 0-1 at 3 months), when compared to patients treated with standard treatment.
2 To assess the safety of ST plus MB treatment, in terms of mortality and of Hemorrhagic transformation rate (symptomatic and asymptomatic), within the first 3 month after treatment. Death from any cause will be recorded. |
Valorar el pronostico a corto y largo plazo |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
The main inclusion criteria will be: - All acute (<4,5 hours) ischemic stroke patients in the MCA territory (as depicted by head computed tomography CT or suspected by clinical data) with a disabling neurological deficit measurable by National Institute of Health Stroke Scale (NIHSS) score, that in the opinion of treating physicians require and meet accepted criteria of treatment with a standard 0.9mg/kg dose of iv rtPA. - A documented occlusion of the middle cerebral artery (MCA) documented by TCD and/or angioCT. -The patient or the legal representative signs the written consent to participate -Age ? 18 years -No significant improvement before treatment. -The treatment is initiated within 90 minutes of hospital admission (door-to-needle time ? 90 minutes) -There is no limitation regarding the NIHSS score. Scores under 5 are usually considered mild strokes, but they can be treated if the investigator believes that the measured deficit is important enough to cause disability. The investigator should weight benefits and risks when the score is under 5 and above 22. |
The main inclusion criteria will be: - All acute (<4,5 hours) ischemic stroke patients in the MCA territory (as depicted by head computed tomography CT or suspected by clinical data) with a disabling neurological deficit measurable by National Institute of Health Stroke Scale (NIHSS) score, that in the opinion of treating physicians require and meet accepted criteria of treatment with a standard 0.9mg/kg dose of iv rtPA. - A documented occlusion of the middle cerebral artery (MCA) documented by TCD and/or angioCT. -The patient or the legal representative signs the written consent to participate -Age ? 18 years -No significant improvement before treatment. -The treatment is initiated within 90 minutes of hospital admission (door-to-needle time ? 90 minutes) -There is no limitation regarding the NIHSS score. Scores under 5 are usually considered mild strokes, but they can be treated if the investigator believes that the measured deficit is important enough to cause disability. The investigator should weight benefits and risks when the score is under 5 and above 22. |
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E.4 | Principal exclusion criteria |
Patients will be excluded if they have 1 or more of the following: -severe stroke as indicated on baseline CT imaging or by a NIHSS score > 25 -evidence of hemorrhage on noncontrast head computed tomography CT), -any other standard contraindication for intravenous rtPA therapy, -primary treatment with intra-arterial thrombolysis, -Previous Rankin scale score > 1 and NIHSS < 14 or previous Rankin scale score >2 and NIHSS ? 14 - Rapidly improving neurological symptoms such that the rate of improvement is expected to result in a NIHSS score of <4 at randomization - Coexisting neurological diseases such as dementia or life-threatening illness. - Seizure at symptom onset - History or clinical presentation of intracranial hemorrhage, subarachnoid hemorrhage (even with a normal CT), arteriovenous malformation, aneurysm, spinal cord disease or cerebral neoplasm. Incidental meningioma and microbleeds per se are not exclusion criteria.
- Baseline blood glucose concentration less than 50 mg/dL or greater than 400 mg/dl, that cannot be corrected - Uncontrolled hypertension, defined as systolic blood pressure >185 mm Hg or diastolic blood pressure >110 mm Hg on at least two separate occasions at least 10 min apart, or blood pressure that requires aggressive treatment to reduce it to within these limits - Hereditary or acquired hemorrhagic diathesis - Another stroke, a serious head injury or major surgery within the previous 3 month -Platelet count < 100.000/mm3 -Hemorrhagic retinopathy -Within 10 days of traumatic external heart massage, obstetrical delivery, recent puncture of a non-compressible blood-vessel -Bacterial endocarditis, pericarditis -Acute pancreatitis; documented ulcerative gastrointestinal disease during the last 3 months, esophageal varices -Arterial aneurysm, arterial/venous malformations -Neoplasm with increased bleeding risk -Severe liver disease, including hepatic failure, cirrhosis, portal hypertension and active hepatitis -Major surgery or significant trauma in past 3 months - Contraindication to CT perfusion: Iodinated contrast allergy, renal insufficiency (elevated serum creatinine above normal laboratory levels at each center), non-collaborative patients, pregnancy
-Contraindication based on CT: Intracerebral or subarachnoid haemorrhage, arteriovenous malformation, cerebral aneurysm, tumour or non-ischaemic lesions mimicking stroke. Infarct core of more than 2/3 of middle cerebral artery territory or all of anterior cerebral artery territory. Any other contraindication to the imaging technique. |
Patients will be excluded if they have 1 or more of the following: -severe stroke as indicated on baseline CT imaging or by a NIHSS score > 25 -evidence of hemorrhage on noncontrast head computed tomography CT), -any other standard contraindication for intravenous rtPA therapy, -primary treatment with intra-arterial thrombolysis, -Previous Rankin scale score > 1 and NIHSS < 14 or previous Rankin scale score >2 and NIHSS ? 14 - Rapidly improving neurological symptoms such that the rate of improvement is expected to result in a NIHSS score of <4 at randomization - Coexisting neurological diseases such as dementia or life-threatening illness. - Seizure at symptom onset - History or clinical presentation of intracranial hemorrhage, subarachnoid hemorrhage (even with a normal CT), arteriovenous malformation, aneurysm, spinal cord disease or cerebral neoplasm. Incidental meningioma and microbleeds per se are not exclusion criteria.
- Baseline blood glucose concentration less than 50 mg/dL or greater than 400 mg/dl, that cannot be corrected - Uncontrolled hypertension, defined as systolic blood pressure >185 mm Hg or diastolic blood pressure >110 mm Hg on at least two separate occasions at least 10 min apart, or blood pressure that requires aggressive treatment to reduce it to within these limits - Hereditary or acquired hemorrhagic diathesis - Another stroke, a serious head injury or major surgery within the previous 3 month -Platelet count < 100.000/mm3 -Hemorrhagic retinopathy -Within 10 days of traumatic external heart massage, obstetrical delivery, recent puncture of a non-compressible blood-vessel -Bacterial endocarditis, pericarditis -Acute pancreatitis; documented ulcerative gastrointestinal disease during the last 3 months, esophageal varices -Arterial aneurysm, arterial/venous malformations -Neoplasm with increased bleeding risk -Severe liver disease, including hepatic failure, cirrhosis, portal hypertension and active hepatitis -Major surgery or significant trauma in past 3 months - Contraindication to CT perfusion: Iodinated contrast allergy, renal insufficiency (elevated serum creatinine above normal laboratory levels at each center), non-collaborative patients, pregnancy
-Contraindication based on CT: Intracerebral or subarachnoid haemorrhage, arteriovenous malformation, cerebral aneurysm, tumour or non-ischaemic lesions mimicking stroke. Infarct core of more than 2/3 of middle cerebral artery territory or all of anterior cerebral artery territory. Any other contraindication to the imaging technique. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Recanalization rate - TIBI score |
Tasa de recanalización arterial |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
1 hour and 6 hours |
1 y 6 horas |
|
E.5.2 | Secondary end point(s) |
Short term clinical outcome Long term clinical outcome Mortality |
Pronóstico corto plazo pronóstico largo plazo mortalidad |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
24 hours and 3 months |
24 horas y 3 meses |
|
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
tratamiento trombolítico estandar |
standard thrombolytic treatment |
|
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 | 1 |
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 | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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
|
The study ends with the 90-days follow-up visit, in which the long term outcome is obtained. In this last visit the Rankin scale score is obtained. Also, the investigator must obtain the NIHSS score, record concomitant medication and adverse events and check vital signs. |
The study ends with the 90-days follow-up visit, in which the long term outcome is obtained. In this last visit the Rankin scale score is obtained. Also, the investigator must obtain the NIHSS score, record concomitant medication and adverse events and check vital signs. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |