Aneurysmal Subarachnoid Hemorrhage
Conditions
Brief summary
This study will evaluate if clazosentan (on top of normal routine medical care) can reduce the risk of developing complications related to cerebral vasospasm and permanent brain damage as compared to normal routine medical care alone.
Detailed description
When a blood vessel just outside the brain bursts and causes bleeding onto its surface, the space surrounding the brain (the subarachnoid space) fills with blood. This condition is called subarachnoid hemorrhage. The bleeding due to the rupture of a pouch-like structure or a bulge (called an aneurysm) that formed on one of the blood vessels is condition called aneurysmal subarachnoid hemorrhage (aSAH). In this study, clazosentan is being tested against normal routine medical care to determine if clazosentan can reduce the risk of developing complications related to vasospasm and permanent brain damage. Participation will last for approximately 6 months from the episode of bleeding. For subjects randomized in the high-risk prevention group, treatment will start within 96 hours following the time of the aneurysm rupture, and be administered where possible, for 14 days. For subjects randomized in the early treatment group, treatment must begin within 24 hours of the time of the angiogram documenting the cerebral vasospasm necessary for entry into the study. Treatment will be administered for a minimum of 6 days and a maximum of 14 days. Recruitment in the early treatment group has been discontinued. The end-of-study will be conducted as a telephone interview 6 months after the episode of bleeding.
Interventions
DRUGClazosentan
Clazosentan will be administered as a continuous intravenous infusion at the dose of 15 mg/hour for up to 14 days.
DRUGPlacebo
Placebo will be administered at the same infusion rate as clazosentan for up to 14 days.
Sponsors
Idorsia Pharmaceuticals Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
This study will be performed in a double-blind fashion. The investigator, study personnel, subjects, clinical research associates (CRAs), sponsor personnel, and vendor / Contract Research Organization (CRO) personnel involved in the conduct of the study will remain blinded to the study treatment received by the subjects during the double-blind treatment period until study closure
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Written informed consent to participate in the study must be obtained from the subject or proxy/legal representative at any time from hospital admission to prior to initiation of any study-mandated procedure, * Males and females aged 18 to 70 years (inclusive, at hospital admission), * Participants with a ruptured saccular aneurysm, angiographically confirmed by DSA or CTA, which has been successfully secured within 72 hours of rupture, by surgical clipping or endovascular coiling, * WFNS (World Federation of Neurosurgical Societies) grades 1-4 (based on Glasgow Coma Scale \[GCS\]) assessed after recovery from the aneurysm-securing procedure and after external ventricular drainage for hydrocephalus, if required. * Participants must meet the criteria for the high-risk prevention group: Subjects with a thick and diffuse clot (thick and diffuse is defined as a thick confluent clot, more than 4 mm in thickness, involving 3 or more basal cisterns) on the hospital admission CT scan, absence of cerebral vasospasm at the time of randomization, and possibility to start study drug in the ICU (or equivalent environment where all protocol assessments can be performed and the Patient Management Guidelines followed), within 96 hours after the time of the aneurysm rupture. * The recruitment into the early treatment group, i.e. participants without a thick and diffuse clot on the hospital admission CT scan who develop asymptomatic or minimally symptomatic moderate to severe angiographic vasospasm, within the 14-day period post-aneurysm rupture, and for whom it is possible to start study drug in the ICU (or equivalent environment where all protocol assessments can be performed and the Patient Management Guidelines followed), within 24 hours of this angiographic diagnosis, has been discontinued. * Presence of a cerebral CT scan performed at least 8 hours post aneurysm securing procedure and within 24 hours prior to randomization. * Absence of a significant (e.g., symptomatic or large) new or worsened cerebral infarct or re-bleeding of the repaired aneurysm on the post-procedure CT scan. * A woman of childbearing potential is eligible only if the pregnancy test performed during the screening period is negative. Agreement must be obtained to take the necessary precautions to avoid pregnancy from hospital discharge until 30 days post-study drug discontinuation. If breastfeeding, agreement must be obtained to refrain for the duration of the treatment with study drug and until 30 days post-study drug discontinuation. * Males are eligible for study participation only if they agree to take the necessary precautions to avoid pregnancy in a female partner from hospital discharge until 30 days post-study drug discontinuation.
Exclusion criteria
* Aneurysmal subarachnoid hemorrhage (aSAH), aneurysm-securing procedure, vasospasm: * Participants with SAH due to causes other than a saccular aneurysm (e.g., trauma or rupture of fusiform or mycotic aneurysms, SAH associated with arterio-venous malformation, vertebral dissections), * Significant bleeding post aneurysm-securing procedure (e.g., due to intra-ventricular drain, intra-cerebral hemorrhage, epidural hematoma, vessel dissection or rupture, re-bleeding of the repaired aneurysm), based on investigator judgment, * Intra-or peri-aneurysm securing procedure complication requiring non-routine medical or interventional treatment such as administration of an antithrombotic or anti-platelet agent (e.g., abciximab), which is not completely resolved prior to randomization, * Intraventricular hemorrhage on the hospital admission CT scan, filling more than 50% of both lateral ventricles and with involvement of the 3rd and 4th ventricles. * Intracerebral hemorrhage on the hospital admission CT scan, with an approximate volume of \> 50 mL, * Presence of cerebral vasospasm at hospital admission (initial admission or transfer from another hospital) believed to be associated with a prior bleed (i.e., occurring before the bleed for which the subject is currently hospitalized). Vasospasm occurring during the aneurysm securing procedure is not an exclusion criterion, * Neurological and functional status: * Participants with a new major neurological deficit occurring post aneurysm-securing procedure which is attributable to the procedure and does not improve to pre-procedure status before randomization, * Participants with a GCS score of ≤ 9 at the time of randomization and without intracranial pressure (ICP) monitoring, * Modified Rankin Score of 3 or higher, prior to the aSAH (i.e., due to a chronic condition), * Other clinical considerations: * Participants with total bilirubin \> 2 times the upper limit of normal, and/or a known diagnosis or clinical suspicion of liver cirrhosis or moderate to severe hepatic impairment, * Hypotension (systolic blood pressure \[SBP\] ≤ 90 mmHg) at time of randomization that is refractory to treatment, * Unresolved pulmonary edema or significant pneumonia still present at the time of randomization, or severe hypoxia at the time of randomization in intubated subjects, defined as PaO2/FiO2 ≤ 200, * High sustained ICP (\> 25 mmHg lasting \> 20 minutes) at time of randomization, despite optimal treatment, in subjects with ICP monitoring, * Severe cardiac failure requiring inotropic support at the time of random
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of Clinical Deterioration Due to Delayed Cerebral Ischemia (DCI) From Study Drug Initiation up to 14 Days Post-study Drug Initiation | Up to 14 days post-study drug initiation | Clinical deterioration due to delayed cerebral ischemia is defined as a worsening of at least 2 points compared to the reference score, on the modified Glasgow Coma Scale or the abbreviated National Institutes of Health Stroke Scale (aNIHSS), lasting for at least 2 hours, which cannot be entirely attributed to causes other than cerebral vasospasm. It is centrally adjudicated by the Clinical Event Committee (CEC) based on a written charter and review of clinical data, case narratives, angiograms and Computed Tomography scans. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of Clinically Relevant Cerebral Infarction at Day 16 Post-study Drug Initiation | At Day 16 post study drug initiation | A clinical relevant cerebral infarction was defined as: all-cause cerebral infraction greater than or equal to 5 cm\^3 or cerebral infarction less than 5 cm\^3 in participants with clinical deterioration due to delayed cerebral ischemia. Cerebral infarction refers to new or worsened infarcts and was determined by a central radiology review comparing the total volume of infarcts on the computed tomography (CT) scan performed 16 days after study drug initiation with the total volume on the CT scan performed just prior to randomization. |
| Long-term Clinical Outcome Assessed by the Modified Rankin Scale (mRS) at Week 12 Post-aneurysmal Subarachnoid Hemorrhage (aSAH) | At Week 12 post-aneurysmal subarachnoid hemorrhage (aSAH) | The modified Rankin Scale (mRS) was used to measure the degree of disability in participants who had a ruptured saccular aneurysm and were at a high risk of developing a delayed cerebral infarction (DCI). The mRS is scored by the physician. The mRS scores ranged from 0 (no symptoms) to 6 (dead). The mRS score was dichotomized into poor outcome (score greater and equal to 3) and good outcome (score less than 3). |
| Long-term Clinical Outcome Assessed by the Glasgow Outcome Scale Extended (GOSE) at Week 12 Post-aSAH | At Week 12 post-aneurysmal subarachnoid hemorrhage (aSAH) | The Glasgow Outcome Scale - Extended (GOSE) is a scale scored by the physician. The GOSE scores range from 1 (dead) to 8 (upper good recovery). The long-term clinical outcome assessed by the GOSE was dichotomized into poor outcome (score ≤ 4) and good outcome (score \> 4) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of Clinical Deterioration Due to Delayed Cerebral Ischemia (DCI) From Study Drug Initiation up to 14 Days Post-study Drug Initiation Based on Neurological Scales and Death | Up to 14 days post-study drug initiation | Clinical deterioration due to delayed cerebral ischemia is defined as a worsening of at least 2 points compared to the reference score, on the modified Glasgow Coma Scale or the abbreviated National Institutes of Health Stroke Scale (aNIHSS), lasting for at least 2 hours, which cannot be entirely attributed to causes other than cerebral vasospasm. It is centrally adjudicated by the Clinical Event Committee (CEC) based on a written charter and review of clinical data, case narratives, angiograms and Computed Tomograph (CT) scans. |
| Occurrence of Clinical Deterioration Due to Delayed Cerebral Ischemia (DCI) From Study Drug Initiation up to 14 Days Post-study Drug Initiation (Safety Analysis Set) | Up to 14 days post-study drug initiation | Clinical deterioration due to delayed cerebral ischemia is defined as a worsening of at least 2 points compared to the reference score, on the modified Glasgow Coma Scale or the abbreviated National Institutes of Health Stroke Scale (aNIHSS), lasting for at least 2 hours, which cannot be entirely attributed to causes other than cerebral vasospasm. It is centrally adjudicated by the Clinical Event Committee (CEC) based on a written charter and review of clinical data, case narratives, angiograms and computed tomography (CT) scans. |
| Occurrence of Clinical Deterioration Due to Delayed Cerebral Ischemia (DCI) From Study Drug Initiation up to 14 Days Post-study Drug Initiation Including Rescue Therapy for Non-relevant Vasospasm | Up to 14 days post-study drug initiation | Clinical deterioration due to delayed cerebral ischemia is defined as a worsening of at least 2 points compared to the reference score, on the modified Glasgow Coma Scale or the abbreviated National Institutes of Health Stroke Scale (aNIHSS), lasting for at least 2 hours, which cannot be entirely attributed to causes other than cerebral vasospasm. It is centrally adjudicated by the Clinical Event Committee (CEC) based on a written charter and review of clinical data, case narratives, angiograms and Computed Tomograph (CT) scans. |
Countries
Austria, Belgium, Canada, Czechia, Denmark, Finland, France, Germany, Hungary, Israel, Italy, Poland, Spain, Sweden, United States
Participant flow
Recruitment details
The study was conducted from 03 February 2019 to 18 November 2022.
Pre-assignment details
Of 453 participants screened, 409 were enrolled in the study and randomized to study treatment.
Participants by arm
| Arm | Count |
|---|---|
| Clazosentan All participants from the randomized analysis set who started clazosentan 15 mg per hour infusion for up to 14 days. | 202 |
| Placebo All participants from the randomized analysis set who started matching placebo infusion for up to 14 days. | 204 |
| Total | 406 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 2 |
| Overall Study | Death | 5 | 3 |
| Overall Study | Lost to Follow-up | 1 | 4 |
| Overall Study | Other reasons | 2 | 2 |
| Overall Study | Withdrawal by proxy/legal representative | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 6 |
Baseline characteristics
| Characteristic | Total | Clazosentan | Placebo |
|---|---|---|---|
| Age, Continuous | 53.3 years STANDARD_DEVIATION 10.2 | 53.0 years STANDARD_DEVIATION 10.4 | 53.7 years STANDARD_DEVIATION 10 |
| Age, Customized 85 years and older | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Between 18 and 64 years | 346 Participants | 171 Participants | 175 Participants |
| Age, Customized Between 65 to 84 years | 60 Participants | 31 Participants | 29 Participants |
| Aneurysmal subarachnoid hemorrhage diagnosed subgroups Confirmed vasospasm group | 11 Participants | 6 Participants | 5 Participants |
| Aneurysmal subarachnoid hemorrhage diagnosed subgroups High risk of vasospasm (high-risk prevention) group | 395 Participants | 196 Participants | 199 Participants |
| Body Mass Index | 26.8 kilograms per square meter STANDARD_DEVIATION 5.6 | 26.8 kilograms per square meter STANDARD_DEVIATION 5.7 | 26.8 kilograms per square meter STANDARD_DEVIATION 5.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 48 Participants | 25 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 314 Participants | 155 Participants | 159 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 44 Participants | 22 Participants | 22 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 10 Participants | 4 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants | 6 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 37 Participants | 16 Participants | 21 Participants |
| Race (NIH/OMB) White | 345 Participants | 176 Participants | 169 Participants |
| Region of Enrollment Austria | 12 participants | 6 participants | 6 participants |
| Region of Enrollment Belgium | 32 participants | 15 participants | 17 participants |
| Region of Enrollment Canada | 20 participants | 8 participants | 12 participants |
| Region of Enrollment Czechia | 47 participants | 23 participants | 24 participants |
| Region of Enrollment Denmark | 5 participants | 2 participants | 3 participants |
| Region of Enrollment Finland | 25 participants | 14 participants | 11 participants |
| Region of Enrollment France | 33 participants | 15 participants | 18 participants |
| Region of Enrollment Germany | 42 participants | 26 participants | 16 participants |
| Region of Enrollment Hungary | 7 participants | 4 participants | 3 participants |
| Region of Enrollment Israel | 13 participants | 6 participants | 7 participants |
| Region of Enrollment Italy | 29 participants | 11 participants | 18 participants |
| Region of Enrollment Poland | 16 participants | 5 participants | 11 participants |
| Region of Enrollment Spain | 48 participants | 24 participants | 24 participants |
| Region of Enrollment Sweden | 18 participants | 8 participants | 10 participants |
| Region of Enrollment United States | 59 participants | 35 participants | 24 participants |
| Sex: Female, Male Female | 275 Participants | 138 Participants | 137 Participants |
| Sex: Female, Male Male | 131 Participants | 64 Participants | 67 Participants |
| Total Glasgow Coma Scale (GCS) Score | 13.2 units on a scale STANDARD_DEVIATION 3.2 | 13.4 units on a scale STANDARD_DEVIATION 3 | 13.1 units on a scale STANDARD_DEVIATION 3.3 |
| World Federation of Neurological Societies (WFNS) Grade Grade I and II | 319 Participants | 161 Participants | 158 Participants |
| World Federation of Neurological Societies (WFNS) Grade Grade III to V | 87 Participants | 41 Participants | 46 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 7 / 207 | 3 / 199 |
| other Total, other adverse events | 156 / 207 | 140 / 199 |
| serious Total, serious adverse events | 33 / 207 | 26 / 199 |
Outcome results
Primary
Occurrence of Clinical Deterioration Due to Delayed Cerebral Ischemia (DCI) From Study Drug Initiation up to 14 Days Post-study Drug Initiation
Clinical deterioration due to delayed cerebral ischemia is defined as a worsening of at least 2 points compared to the reference score, on the modified Glasgow Coma Scale or the abbreviated National Institutes of Health Stroke Scale (aNIHSS), lasting for at least 2 hours, which cannot be entirely attributed to causes other than cerebral vasospasm. It is centrally adjudicated by the Clinical Event Committee (CEC) based on a written charter and review of clinical data, case narratives, angiograms and Computed Tomography scans.
Time frame: Up to 14 days post-study drug initiation
Population: Full Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Clazosentan | Occurrence of Clinical Deterioration Due to Delayed Cerebral Ischemia (DCI) From Study Drug Initiation up to 14 Days Post-study Drug Initiation | 32 Participants |
| Placebo | Occurrence of Clinical Deterioration Due to Delayed Cerebral Ischemia (DCI) From Study Drug Initiation up to 14 Days Post-study Drug Initiation | 35 Participants |
p-value: 0.733895% CI: [-0.426, 0.396]Cochran-Mantel-Haenszel
Secondary
Long-term Clinical Outcome Assessed by the Glasgow Outcome Scale Extended (GOSE) at Week 12 Post-aSAH
The Glasgow Outcome Scale - Extended (GOSE) is a scale scored by the physician. The GOSE scores range from 1 (dead) to 8 (upper good recovery). The long-term clinical outcome assessed by the GOSE was dichotomized into poor outcome (score ≤ 4) and good outcome (score \> 4)
Time frame: At Week 12 post-aneurysmal subarachnoid hemorrhage (aSAH)
Population: Full Analysis Set
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Clazosentan | Long-term Clinical Outcome Assessed by the Glasgow Outcome Scale Extended (GOSE) at Week 12 Post-aSAH | Participants with a GOSE score less than and equal to 4 | 50 Participants |
| Clazosentan | Long-term Clinical Outcome Assessed by the Glasgow Outcome Scale Extended (GOSE) at Week 12 Post-aSAH | Participant with a GOSE score greater than 4 | 152 Participants |
| Placebo | Long-term Clinical Outcome Assessed by the Glasgow Outcome Scale Extended (GOSE) at Week 12 Post-aSAH | Participants with a GOSE score less than and equal to 4 | 41 Participants |
| Placebo | Long-term Clinical Outcome Assessed by the Glasgow Outcome Scale Extended (GOSE) at Week 12 Post-aSAH | Participant with a GOSE score greater than 4 | 163 Participants |
p-value: 0.198395% CI: [-0.76, 0.107]Cochran-Mantel-Haenszel
Secondary
Long-term Clinical Outcome Assessed by the Modified Rankin Scale (mRS) at Week 12 Post-aneurysmal Subarachnoid Hemorrhage (aSAH)
The modified Rankin Scale (mRS) was used to measure the degree of disability in participants who had a ruptured saccular aneurysm and were at a high risk of developing a delayed cerebral infarction (DCI). The mRS is scored by the physician. The mRS scores ranged from 0 (no symptoms) to 6 (dead). The mRS score was dichotomized into poor outcome (score greater and equal to 3) and good outcome (score less than 3).
Time frame: At Week 12 post-aneurysmal subarachnoid hemorrhage (aSAH)
Population: Full Analysis Set.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Clazosentan | Long-term Clinical Outcome Assessed by the Modified Rankin Scale (mRS) at Week 12 Post-aneurysmal Subarachnoid Hemorrhage (aSAH) | Participants with a mRS score of equal and greater than 3 | 50 Participants |
| Clazosentan | Long-term Clinical Outcome Assessed by the Modified Rankin Scale (mRS) at Week 12 Post-aneurysmal Subarachnoid Hemorrhage (aSAH) | Participants with a mRS score of less than 3 | 152 Participants |
| Placebo | Long-term Clinical Outcome Assessed by the Modified Rankin Scale (mRS) at Week 12 Post-aneurysmal Subarachnoid Hemorrhage (aSAH) | Participants with a mRS score of equal and greater than 3 | 41 Participants |
| Placebo | Long-term Clinical Outcome Assessed by the Modified Rankin Scale (mRS) at Week 12 Post-aneurysmal Subarachnoid Hemorrhage (aSAH) | Participants with a mRS score of less than 3 | 163 Participants |
p-value: 0.198395% CI: [-0.76, 0.107]Cochran-Mantel-Haenszel
Secondary
Occurrence of Clinically Relevant Cerebral Infarction at Day 16 Post-study Drug Initiation
A clinical relevant cerebral infarction was defined as: all-cause cerebral infraction greater than or equal to 5 cm\^3 or cerebral infarction less than 5 cm\^3 in participants with clinical deterioration due to delayed cerebral ischemia. Cerebral infarction refers to new or worsened infarcts and was determined by a central radiology review comparing the total volume of infarcts on the computed tomography (CT) scan performed 16 days after study drug initiation with the total volume on the CT scan performed just prior to randomization.
Time frame: At Day 16 post study drug initiation
Population: Full Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Clazosentan | Occurrence of Clinically Relevant Cerebral Infarction at Day 16 Post-study Drug Initiation | 15 Participants |
| Placebo | Occurrence of Clinically Relevant Cerebral Infarction at Day 16 Post-study Drug Initiation | 23 Participants |
p-value: 0.17795% CI: [-0.213, 0.642]Cochran-Mantel-Haenszel
Other Pre-specified
Occurrence of Clinical Deterioration Due to Delayed Cerebral Ischemia (DCI) From Study Drug Initiation up to 14 Days Post-study Drug Initiation Based on Neurological Scales and Death
Clinical deterioration due to delayed cerebral ischemia is defined as a worsening of at least 2 points compared to the reference score, on the modified Glasgow Coma Scale or the abbreviated National Institutes of Health Stroke Scale (aNIHSS), lasting for at least 2 hours, which cannot be entirely attributed to causes other than cerebral vasospasm. It is centrally adjudicated by the Clinical Event Committee (CEC) based on a written charter and review of clinical data, case narratives, angiograms and Computed Tomograph (CT) scans.
Time frame: Up to 14 days post-study drug initiation
Population: Full Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Clazosentan | Occurrence of Clinical Deterioration Due to Delayed Cerebral Ischemia (DCI) From Study Drug Initiation up to 14 Days Post-study Drug Initiation Based on Neurological Scales and Death | 28 Participants |
| Placebo | Occurrence of Clinical Deterioration Due to Delayed Cerebral Ischemia (DCI) From Study Drug Initiation up to 14 Days Post-study Drug Initiation Based on Neurological Scales and Death | 33 Participants |
p-value: 0.521795% CI: [-0.365, 0.457]Cochran-Mantel-Haenszel
Other Pre-specified
Occurrence of Clinical Deterioration Due to Delayed Cerebral Ischemia (DCI) From Study Drug Initiation up to 14 Days Post-study Drug Initiation Including Rescue Therapy for Non-relevant Vasospasm
Clinical deterioration due to delayed cerebral ischemia is defined as a worsening of at least 2 points compared to the reference score, on the modified Glasgow Coma Scale or the abbreviated National Institutes of Health Stroke Scale (aNIHSS), lasting for at least 2 hours, which cannot be entirely attributed to causes other than cerebral vasospasm. It is centrally adjudicated by the Clinical Event Committee (CEC) based on a written charter and review of clinical data, case narratives, angiograms and Computed Tomograph (CT) scans.
Time frame: Up to 14 days post-study drug initiation
Population: Full Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Clazosentan | Occurrence of Clinical Deterioration Due to Delayed Cerebral Ischemia (DCI) From Study Drug Initiation up to 14 Days Post-study Drug Initiation Including Rescue Therapy for Non-relevant Vasospasm | 34 Participants |
| Placebo | Occurrence of Clinical Deterioration Due to Delayed Cerebral Ischemia (DCI) From Study Drug Initiation up to 14 Days Post-study Drug Initiation Including Rescue Therapy for Non-relevant Vasospasm | 47 Participants |
p-value: 0.117995% CI: [-0.085, 0.505]Cochran-Mantel-Haenszel
Other Pre-specified
Occurrence of Clinical Deterioration Due to Delayed Cerebral Ischemia (DCI) From Study Drug Initiation up to 14 Days Post-study Drug Initiation (Safety Analysis Set)
Clinical deterioration due to delayed cerebral ischemia is defined as a worsening of at least 2 points compared to the reference score, on the modified Glasgow Coma Scale or the abbreviated National Institutes of Health Stroke Scale (aNIHSS), lasting for at least 2 hours, which cannot be entirely attributed to causes other than cerebral vasospasm. It is centrally adjudicated by the Clinical Event Committee (CEC) based on a written charter and review of clinical data, case narratives, angiograms and computed tomography (CT) scans.
Time frame: Up to 14 days post-study drug initiation
Population: Safety Analysis Set: all randomized participants who started study treatment, evaluated according to the actual treatment received. Note that 5 participants randomized to placebo received at least 1 infusion of clazosentan and were analyzed as part of the clazosentan arm for this analysis set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Clazosentan | Occurrence of Clinical Deterioration Due to Delayed Cerebral Ischemia (DCI) From Study Drug Initiation up to 14 Days Post-study Drug Initiation (Safety Analysis Set) | 32 Participants |
| Placebo | Occurrence of Clinical Deterioration Due to Delayed Cerebral Ischemia (DCI) From Study Drug Initiation up to 14 Days Post-study Drug Initiation (Safety Analysis Set) | 35 Participants |
p-value: 0.559195% CI: [-0.349, 0.425]Cochran-Mantel-Haenszel