Carbonic Anhydrase Antagonism in Subarachnoid Hemorrhage

Withdrawn

Phase 2 Results N/A

Trial Description

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.
1. Modified Rankin Scale (m-RS) scores
2. Glasgow Outcome Scale (GOS) scores

Trial Stopped: The PI is leaving the University of Florida.

Conditions

Interventions

  • Nimodipine (NimotopĀ®)Drug
    Intervention Desc: Nimodipine 60 mg orally every 4 hours, with therapy starting within 96 hours of the event and continued for 21 days
    ARM 1: Kind: Experimental
    Label: Acetazolamide
    Description: 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.
    ARM 2: Kind: Experimental
    Label: Standard of care
    Description: 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.
  • Acetazolamide Drug
    Other Names: Diamox
    Intervention Desc: 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.
    ARM 1: Kind: Experimental
    Label: Acetazolamide
    Description: 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.

Trial Design

  • Allocation: Randomized
  • Masking: Open Label
  • Purpose: Treatment
  • Endpoint: Efficacy Study
  • Intervention: Parallel Assignment

Outcomes

Type Measure Time Frame Safety Issue
Primary Modified Rankin Score At 3 months from the baseline Yes
Primary Neurological examination of the subject Baseline, 10 days, 3 months Yes
Primary Glasgow Outcome Score At 3 months from the baseline Yes
Primary Hunt and Hess Scale Baseline, 10 days Yes
Primary World Federation of Neurosurgeons Scale Baseline, 10 days Yes

Sponsors