Acute Cerebrovascular AccidentPhase 2NCT02165644
Carbonic Anhydrase Antagonism in Subarachnoid Hemorrhage
A Phase 2 study testing Acetazolamide and Nimodipine in people with Acute Cerebrovascular Accident and Vasospasm, run by University of Florida.
Trial summary
Subarachnoid Hemorrhage (SAH) can occur commonly in the setting of trauma or brain aneurysm. SAH accounts for 10% of all the strokes. Aneurysmal SAH accounts for 80 % of cases of non-traumatic cases of SAH, 6-8% of all strokes and 22-25% of all cerebrovascular deaths. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Acute Cerebrovascular Accident, Vasospasm
- What is being tested?
- Acetazolamide and Nimodipine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Sep 2015to Sep 2015
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All aneurysmal SAH patients with clinical and or radiological diagnosis.
- Subjects with age ≥18 years and ≤80 years at the time of screening.
- The subject or his/ her legal representative is willing to undergo informed consent process prior to enrollment into this study.
- World Federation of Neurosurgeons scale score ≤ 2
- Hunt and Hess Stroke scale score ≤ 2
- Mean velocities of < 200 cm/s in at least 1 vascular axis of the circle of Willis
- Patients admitted within 4 days of symptom onset.
Who cannot join
- Subject with age < 18 years and >80 years at the time of screening.
- Time of symptom onset cannot be determined.
- Subject who is pregnant or lactating.
- Subjects who have hypersensitivity to acetazolamide, sulfa drugs, or any component of the formulation.
- Mean velocities of ≥ 200 cm/s in at least 1 vascular axis of the circle of Willis
- Brain CT or MRI show acute infarction
Show all 16Show fewer
- Any acute focal neurological deficit (including any one of these) speech problems, loss of vision, facial or extremity weakness.
- Hunt and Hess Stroke scale scores > 2
- World Federation of Neurosurgeons scale scores > 2
- Subjects with hepatic disease or insufficiency or cirrhosis.
- Subjects with severe renal disease or dysfunction.
- Subjects who have decreased sodium and/or potassium levels; hyperchloremic acidosis.
- Subjects who have adrenocortical insufficiency.
- The subject or legal representative is unable to provide informed consent.
- The subject is medically unstable to participate in the trial as determined by the principal investigator.
- The subject has any end stage medical condition as determined by the principal investigator.
About this study
Official title: Targeting Carbonic Anhydrase Mediated Coupling as a Novel Vasospasm Prophylaxis in Aneurysmal Sub Arachnoid Hemorrhage
Subarachnoid Hemorrhage (SAH) can occur commonly in the setting of trauma or brain aneurysm. SAH accounts for 10% of all the strokes. Aneurysmal SAH accounts for 80 % of cases of non-traumatic cases of SAH, 6-8% of all strokes and 22-25% of all cerebrovascular deaths. Mortality can be 50% in the first few years of aneurysmal SAH rupture, 15% are severely disabled post SAH and only 20-35% having a moderate to good recovery it has gained lot of attention and pre-clinical and clinical trials of various agents have been tried to prevent poor outcome. The United States epidemiology data reveals the fact that 1% to 5% of adults have unruptured brain aneurysm and 30,000 people suffer from aneurysm rupture annually translating to brain aneurysm rupture every 18 minutes.
Vasospasm is the most common SAH complication post 24 hours. It is the segmental or diffuse narrowing of the vessels especially the large vessels. Fifty percent of those patients who develop clinical vasospasm, progress to infarction and 15-20% will advance to disabling stroke or die of cerebral ischemia. The present treatment modalities are insufficient to prevent vasospasm. So, we need new treatment modalities to decrease the mortality and morbidity in SAH patients.
The investigators hypothesize that Acetazolamide administration can prevent development of vasospasm after aneurysmal SAH.
Read the detailed description
If the subject decides to take part in this study, they will receive acetazolamide with standard of care or standard of care only for four days. This means:
The subject will be given acetazolamide tablet orally with standard care for subarachnoid hemorrhage or standard of care only, for a maximum of 4 days. If the subject cannot take medication orally then the investigators will put a tube through the nose to stomach or small intestine. Being part of the study does not exclude the subject from receiving the standard therapy. The subject will be given the current standard of care therapy irrespective of being in the study or not. The investigators will review the subject's medical records and collect information from standard of care procedures that would have been done even if the subject were not enrolled in this study. This information will include, but will not be limited to, the subject's imaging data, sub arachnoid hemorrhage assessments and medical history. The subject's Hunt and Hess scale score and (World federation of neurologic surgeons) WFNS scale score will also be collected. Hunt and Hess and WFNS scale are used to assess the level of damage to neurologic functions of a person caused by sub arachnoid hemorrhage.
The subject will be asked to come for the follow-up at 3 months after the discharge from the hospital. The following data will be obtained from each subject at 3-month follow-up.
- Modified Rankin Scale (m-RS) scores
- Glasgow Outcome Scale (GOS) scores
- Conditions
- Acute Cerebrovascular Accident, Vasospasm
- Being tested
- Acetazolamide, Nimodipine
- Keywords
- Subarachnoid Hemorrhage, Vasospasm, Acetazolamide
- Medical subject headings
- Stroke, Subarachnoid Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AcetazolamideDrug
Also called Diamox
Acetazolamide 250 mg QID oral for 4 days along with standard of care which includes Nimodipine 60 mg orally every 4 hours, with therapy starting within 96 hours of the event and continued for 21 days.
If the drug can't be given orally, then feeding tube (NG Tube or DHT) will be used for drug administration.
NimodipineDrug
Also called Nimotop
Nimodipine 60 mg orally every 4 hours, with therapy starting within 96 hours of the event and continued for 21 days
| Study group | Role | What they receive |
|---|---|---|
| Acetazolamide | Experimental | Acetazolamide 250 mg QID oral for 4 days along with current standard of care which is Nimodipine 60 mg orally every 4 hours, with therapy starting within 96 hours of the event and continued for 21 days.
If the drug can't be given orally, then feeding tube (NG Tube or DHT) will be used for drug administration. Receives: Drug: Acetazolamide; Drug: Nimodipine |
| Standard of care | Active comparator | Subjects will receive only standard of care for subarachnoid hemorrhage which will include Nimodipine 60 mg orally every 4 hours, with therapy starting within 96 hours of the event and continued for 21 days. Receives: Drug: Nimodipine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Modified Rankin Score
The modified Rankin Scale (m-RS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people after they have suffered a stroke including subarachnoid hemorrhage. The score is given according to following scale.
0- No symptoms at all
- No significant disability despite symptoms; able to carry out all usual duties and activities
- Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance
- Moderate disability; requiring some help, but able to walk without assistance
- Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance
- Severe disability; bedridden, incontinent and requiring constant nursing care and attention
- Dead
Measured: At 3 months from the baseline
Neurological examination of the subject
Neurological status of a subject is assessed by physical neurological examination of the subject by a qualified neurologist. It is one of the most important aspect in determining neurological health of a subject after subarachnoid hemorrhage. It also helps to determine subarachnoid hemorrhage severity and prognosis.
Measured: Baseline, 10 days, 3 months
Glasgow Outcome Score
The Glasgow Outcome Scale (GOS) was developed to rank outcomes after head injury, but has been used in stroke studies including subarachnoid hemorrhage. The score is given according to following scale ranging from 1-5.
- Death- Severe injury or death without recovery of consciousness
- Persistent vegetative state- Severe damage with prolonged state of unresponsiveness and a lack of higher mental functions
- Severe disability- Severe injury with permanent need for help with daily living
- Moderate disability- No need for assistance in everyday life, employment is possible but may require special equipment.
- Low disability- Light damage with minor neurological and psychological deficits.
Measured: At 3 months from the baseline
Hunt and Hess Scale
The Hunt and Hess scale, is one of the grading systems used to classify the severity of a subarachnoid hemorrhage based on the patient's clinical condition. It is used as a predictor of patient's prognosis/outcome, with a higher grade correlating to lower survival rate. It gives an index of the mortality associated with the various grades. The mortality is minimum with grade 1 and maximum with grade 5. The grades are as follows:
- Asymptomatic, mild headache, slight nuchal rigidity
- Moderate to severe headache, nuchal rigidity, no neurologic deficit other than cranial nerve palsy
- Drowsiness / confusion, mild focal neurologic deficit
- Stupor, moderate-severe hemiparesis
- Coma, decerebrate posturing
Measured: Baseline, 10 days
World Federation of Neurosurgeons Scale
The World Federation of Neurosurgeons (WFNS) classification uses Glasgow coma score (GCS) and focal neurological deficit to gauge severity of symptoms. It is intended to be a simple, reliable and clinically valid way to grade a patient with subarachnoid hemorrhage. The prognosis becomes worse when we move from grade 1 to grade 5.
Grade 1 represents a GCS of 15 with absent focal neurological deficit, Grade 2 represents a GCS of 13-14 with absent focal neurological deficit, Grade 3 represents a GCS of 13-14 with focal neurological deficit present, Grade 4 represents a GCS of 7-12 with present or absent focal neurological deficit, Grade 5 represents a GCS of <7 with present or absent focal neurological deficit.
Measured: Baseline, 10 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jun 2014 (estimated)
- Study startSep 2015
- Primary completionSep 2015
- Study completionSep 2015
Why it stopped: The PI is leaving the University of Florida.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Cerebrovascular AccidentStudies of the same condition, open and under way.
- More trials run by University of FloridaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Vishnumurthy S Hedna, MD, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02165644
- Sponsor's protocol ID
- 2014000419
- Status last verified
- Sep 2015
- First submitted
- 13 Jun 2014
- Last updated
- 24 Sep 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Targeting Carbonic Anhydrase Mediated Coupling as a Novel Vasospasm Prophylaxis in Aneurysmal Sub Arachnoid Hemorrhage
- ClinicalTrials.gov ID
- NCT02165644
- Acronym / sponsor ID
- 2014000419
- Conditions
- Acute Cerebrovascular Accident, Vasospasm
- Keywords
- Subarachnoid Hemorrhage, Vasospasm, Acetazolamide
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: The PI is leaving the University of Florida.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Study start
- Sep 2015
- Primary completion
- Sep 2015 (actual)
- Study completion
- Sep 2015 (actual)
- First posted
- 17 Jun 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Subarachnoid Hemorrhage (SAH) can occur commonly in the setting of trauma or brain aneurysm. SAH accounts for 10% of all the strokes. Aneurysmal SAH accounts for 80 % of cases of non-traumatic cases of SAH, 6-8% of all strokes and 22-25% of all cerebrovascular deaths. Mortality can be 50% in the first few years of aneurysmal SAH rupture, 15% are severely disabled post SAH and only 20-35% having a moderate to good recovery it has gained lot of attention and pre-clinical and clinical trials of various agents have been tried to prevent poor outcome. The United States epidemiology data reveals the fact that 1% to 5% of adults have unruptured brain aneurysm and 30,000 people suffer from aneurysm rupture annually translating to brain aneurysm rupture every 18 minutes.
Vasospasm is the most common SAH complication post 24 hours. It is the segmental or diffuse narrowing of the vessels especially the large vessels. Fifty percent of those patients who develop clinical vasospasm, progress to infarction and 15-20% will advance to disabling stroke or die of cerebral ischemia. The present treatment modalities are insufficient to prevent vasospasm. So, we need new treatment modalities to decrease the mortality and morbidity in SAH patients.
The investigators hypothesize that Acetazolamide administration can prevent development of vasospasm after aneurysmal SAH.
Detailed description
If the subject decides to take part in this study, they will receive acetazolamide with standard of care or standard of care only for four days. This means:
The subject will be given acetazolamide tablet orally with standard care for subarachnoid hemorrhage or standard of care only, for a maximum of 4 days. If the subject cannot take medication orally then the investigators will put a tube through the nose to stomach or small intestine. Being part of the study does not exclude the subject from receiving the standard therapy. The subject will be given the current standard of care therapy irrespective of being in the study or not. The investigators will review the subject's medical records and collect information from standard of care procedures that would have been done even if the subject were not enrolled in this study. This information will include, but will not be limited to, the subject's imaging data, sub arachnoid hemorrhage assessments and medical history. The subject's Hunt and Hess scale score and (World federation of neurologic surgeons) WFNS scale score will also be collected. Hunt and Hess and WFNS scale are used to assess the level of damage to neurologic functions of a person caused by sub arachnoid hemorrhage.
The subject will be asked to come for the follow-up at 3 months after the discharge from the hospital. The following data will be obtained from each subject at 3-month follow-up.
- Modified Rankin Scale (m-RS) scores
- Glasgow Outcome Scale (GOS) scores
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Acetazolamide | Experimental | Drug: Acetazolamide, Drug: NimodipineAcetazolamide 250 mg QID oral for 4 days along with current standard of care which is Nimodipine 60 mg orally every 4 hours, with therapy starting within 96 hours of the event and continued for 21 days. If the drug can't be given orally, then feeding tube (NG Tube or DHT) will be used for drug administration. |
| Standard of care | Active comparator | Drug: NimodipineSubjects will receive only standard of care for subarachnoid hemorrhage which will include Nimodipine 60 mg orally every 4 hours, with therapy starting within 96 hours of the event and continued for 21 days. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- All aneurysmal SAH patients with clinical and or radiological diagnosis.
- Subjects with age ≥18 years and ≤80 years at the time of screening.
- The subject or his/ her legal representative is willing to undergo informed consent process prior to enrollment into this study.
- World Federation of Neurosurgeons scale score ≤ 2
- Hunt and Hess Stroke scale score ≤ 2
Key exclusion criteria (16 listed)
- Subject with age < 18 years and >80 years at the time of screening.
- Time of symptom onset cannot be determined.
- Subject who is pregnant or lactating.
- Subjects who have hypersensitivity to acetazolamide, sulfa drugs, or any component of the formulation.
- Mean velocities of ≥ 200 cm/s in at least 1 vascular axis of the circle of Willis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AcetazolamideAlso: DiamoxAcetazolamide 250 mg QID oral for 4 days along with standard of care which includes Nimodipine 60 mg orally every 4 hours, with therapy starting within 96 hours of the event and continued for 21 days. If the drug can't be given orally, then feeding tube (NG Tube or DHT) will be used for drug administration. | Drug | Acetazolamide |
| NimodipineAlso: NimotopNimodipine 60 mg orally every 4 hours, with therapy starting within 96 hours of the event and continued for 21 days | Drug | Acetazolamide, Standard of care |
Primary outcome
Modified Rankin Score
Time frame: At 3 months from the baseline
The modified Rankin Scale (m-RS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people after they have suffered a stroke including subarachnoid hemorrhage. The score is given according to following scale. 0- No symptoms at all 1. No significant disability despite symptoms; able to carry out all usual duties and activities 2. Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance 3. Moderate disability; requiring some help, but able to walk without assistance 4. Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance 5. Severe disability; bedridden, incontinent and requiring constant nursing care and attention 6. Dead
Neurological examination of the subject
Time frame: Baseline, 10 days, 3 months
Neurological status of a subject is assessed by physical neurological examination of the subject by a qualified neurologist. It is one of the most important aspect in determining neurological health of a subject after subarachnoid hemorrhage. It also helps to determine subarachnoid hemorrhage severity and prognosis.
Glasgow Outcome Score
Time frame: At 3 months from the baseline
The Glasgow Outcome Scale (GOS) was developed to rank outcomes after head injury, but has been used in stroke studies including subarachnoid hemorrhage. The score is given according to following scale ranging from 1-5. 1. Death- Severe injury or death without recovery of consciousness 2. Persistent vegetative state- Severe damage with prolonged state of unresponsiveness and a lack of higher mental functions 3. Severe disability- Severe injury with permanent need for help with daily living 4. Moderate disability- No need for assistance in everyday life, employment is possible but may require special equipment. 5. Low disability- Light damage with minor neurological and psychological deficits.
Hunt and Hess Scale
Time frame: Baseline, 10 days
The Hunt and Hess scale, is one of the grading systems used to classify the severity of a subarachnoid hemorrhage based on the patient's clinical condition. It is used as a predictor of patient's prognosis/outcome, with a higher grade correlating to lower survival rate. It gives an index of the mortality associated with the various grades. The mortality is minimum with grade 1 and maximum with grade 5. The grades are as follows: 1. Asymptomatic, mild headache, slight nuchal rigidity 2. Moderate to severe headache, nuchal rigidity, no neurologic deficit other than cranial nerve palsy 3. Drowsiness / confusion, mild focal neurologic deficit 4. Stupor, moderate-severe hemiparesis 5. Coma, decerebrate posturing
World Federation of Neurosurgeons Scale
Time frame: Baseline, 10 days
The World Federation of Neurosurgeons (WFNS) classification uses Glasgow coma score (GCS) and focal neurological deficit to gauge severity of symptoms. It is intended to be a simple, reliable and clinically valid way to grade a patient with subarachnoid hemorrhage. The prognosis becomes worse when we move from grade 1 to grade 5. Grade 1 represents a GCS of 15 with absent focal neurological deficit, Grade 2 represents a GCS of 13-14 with absent focal neurological deficit, Grade 3 represents a GCS of 13-14 with focal neurological deficit present, Grade 4 represents a GCS of 7-12 with present or absent focal neurological deficit, Grade 5 represents a GCS of <7 with present or absent focal neurological deficit.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Vishnumurthy S Hedna, MD principal investigator
University of Florida
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Acetazolamide and Nimodipine in people with Acute Cerebrovascular Accident and Vasospasm, run by University of Florida.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 24 Sep 2015. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Modified Rankin Score (time frame: At 3 months from the baseline). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Sep 2015.