<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03028298</url>
  </required_header>
  <id_info>
    <org_study_id>2016-0134</org_study_id>
    <nct_id>NCT03028298</nct_id>
  </id_info>
  <brief_title>Sildenafil for DCI</brief_title>
  <official_title>Sildenafil for the Treatment of Delayed Cerebral Ischemia Following Subarachnoid Hemorrhage</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Mississippi Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Mississippi Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Each year, approximately 30,000 people in the United States suffer an intra-cranial&#xD;
      hemorrhage due to aneurysmal rupture. Of those surviving the initial event, up to 40% will go&#xD;
      on to have further neurological injury secondary to stroke (delayed cerebral ischemia) caused&#xD;
      by constriction of blood vessels (i.e. vasospasm). Previous studies have shown that the&#xD;
      medication sildenafil, given intravenously, improves vasospasm, but has an associated degree&#xD;
      of hypotension. The degree of hypotension was well within safety thresholds for these&#xD;
      patients.&#xD;
&#xD;
      Sildenafil is a medication that strongly inhibits the protein phosphodiesterase-V (PDE-V).&#xD;
      The hypothesis for this study is that oral sildenafil will also improve vasospasm, but does&#xD;
      not result in as much hypotension. Specifically, the investigators look to show that&#xD;
      comparable doses of oral sildenafil produces the same degree of PDE-V inhibition as an&#xD;
      intravenous dose while the degree of hypotension is reduced. Additionally, using measurements&#xD;
      of cerebral blood flow regulation acquired using transcranial Doppler ultrasound, the&#xD;
      investigators look to show that oral sildenafil produces the same degree of improvement in&#xD;
      vasospasm and blood flow regulation.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date>December 2016</start_date>
  <completion_date type="Anticipated">July 2023</completion_date>
  <primary_completion_date type="Anticipated">December 2022</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Patients will be randomly assigned to either low dose sildenafil (20mg oral and 10mg intravenous) or high dose sildenafil (60mg oral and 30 mg intravenous)</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from baseline in mean arterial blood pressure</measure>
    <time_frame>baseline and 2 hours post-dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under the plasma concentration versus time curve (AUC) of sildenafil</measure>
    <time_frame>0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 16, 20, and 24 hours post-dose</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Area under the cerebral spinal fluid concentration versus time curve (AUC) of sildenafil</measure>
    <time_frame>0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 16, 20, and 24 hours post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in cerebral autoregulation</measure>
    <time_frame>baseline and 2 hours post-dose</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">24</enrollment>
  <condition>Subarachnoid Hemorrhage</condition>
  <condition>Cerebral Vasospasm</condition>
  <arm_group>
    <arm_group_label>Low dose sildenafil</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Twelve patients with cerebral vasospasm following aneurysmal subarachnoid hemorrhage will be assigned to low dose sildenafil citrate and will receive a 20mg oral dose and a subsequent 10mg intravenous dose of sildenafil citrate.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>High dose sildenafil</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Twelve patients with cerebral vasospasm following aneurysmal subarachnoid hemorrhage will be assigned to high dose sildenafil citrate and will receive a 60mg oral dose and a subsequent 30mg intravenous dose of sildenafil citrate.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Low dose sildenafil citrate</intervention_name>
    <arm_group_label>Low dose sildenafil</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>High dose sildenafil citrate</intervention_name>
    <arm_group_label>High dose sildenafil</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age &gt;= 21&#xD;
&#xD;
          2. Onset of symptoms within 72 hours from presentation&#xD;
&#xD;
          3. Subarachnoid hemorrhage from ruptured cerebral aneurysm&#xD;
&#xD;
          4. Cerebral vasospasm diagnosed on transcranial doppler, CT angiography, or digital&#xD;
             subtraction angiography&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Pregnancy&#xD;
&#xD;
          2. Subarachnoid hemorrhage secondary to traumatic or mycotic aneurysm&#xD;
&#xD;
          3. Pre-ictal sildenafil therapy (last dose within 1 week of presentation)&#xD;
&#xD;
          4. Contraindications to sildenafil therapy (i.e. use of nitrates, left ventricular&#xD;
             outflow obstruction, impaired autonomic blood pressure control)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Chad W Washington, MS, MD, MPHS</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Mississippi Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Mississippi Medical Center</name>
      <address>
        <city>Jackson</city>
        <state>Mississippi</state>
        <zip>39216</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Washington CW, Derdeyn CP, Dhar R, Arias EJ, Chicoine MR, Cross DT, Dacey RG Jr, Han BH, Moran CJ, Rich KM, Vellimana AK, Zipfel GJ. A Phase I proof-of-concept and safety trial of sildenafil to treat cerebral vasospasm following subarachnoid hemorrhage. J Neurosurg. 2016 Feb;124(2):318-27. doi: 10.3171/2015.2.JNS142752. Epub 2015 Aug 28.</citation>
    <PMID>26314998</PMID>
  </reference>
  <reference>
    <citation>Dhar R, Washington C, Diringer M, Zazulia A, Jafri H, Derdeyn C, Zipfel G. Acute Effect of Intravenous Sildenafil on Cerebral Blood Flow in Patients with Vasospasm After Subarachnoid Hemorrhage. Neurocrit Care. 2016 Oct;25(2):201-4. doi: 10.1007/s12028-016-0243-0.</citation>
    <PMID>26940913</PMID>
  </reference>
  <verification_date>June 2021</verification_date>
  <study_first_submitted>January 13, 2017</study_first_submitted>
  <study_first_submitted_qc>January 19, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 23, 2017</study_first_posted>
  <last_update_submitted>June 5, 2021</last_update_submitted>
  <last_update_submitted_qc>June 5, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 8, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Subarachnoid Hemorrhage</mesh_term>
    <mesh_term>Vasospasm, Intracranial</mesh_term>
    <mesh_term>Hemorrhage</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sildenafil Citrate</mesh_term>
    <mesh_term>Citric Acid</mesh_term>
    <mesh_term>Sodium Citrate</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03028298
org study id: 2016-0134
nct id: NCT03028298
lead sponsor: 
has dmc: Yes
Each year, approximately 30,000 people in the United States suffer an intra-cranial
      hemorrhage due to aneurysmal rupture. Of those surviving the initial event, up to 40% will go
      on to have further neurological injury secondary to stroke (delayed cerebral ischemia) caused
      by constriction of blood vessels (i.e. vasospasm). Previous studies have shown that the
      medication sildenafil, given intravenously, improves vasospasm, but has an associated degree
      of hypotension. The degree of hypotension was well within safety thresholds for these
      patients.

      Sildenafil is a medication that strongly inhibits the protein phosphodiesterase-V (PDE-V).
      The hypothesis for this study is that oral sildenafil will also improve vasospasm, but does
      not result in as much hypotension. Specifically, the investigators look to show that
      comparable doses of oral sildenafil produces the same degree of PDE-V inhibition as an
      intravenous dose while the degree of hypotension is reduced. Additionally, using measurements
      of cerebral blood flow regulation acquired using transcranial Doppler ultrasound, the
      investigators look to show that oral sildenafil produces the same degree of improvement in
      vasospasm and blood flow regulation.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Patients will be randomly assigned to either low dose sildenafil (20mg oral and 10mg intravenous) or high dose sildenafil (60mg oral and 30 mg intravenous)
primary purpose: Treatment
masking: None (Open Label)
measure: Change from baseline in mean arterial blood pressure
time frame: baseline and 2 hours post-dose
measure: Area under the plasma concentration versus time curve (AUC) of sildenafil
time frame: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 16, 20, and 24 hours post-dose
measure: Area under the cerebral spinal fluid concentration versus time curve (AUC) of sildenafil
time frame: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 16, 20, and 24 hours post-dose
measure: Change from baseline in cerebral autoregulation
time frame: baseline and 2 hours post-dose
arm group label: Low dose sildenafil
arm group type: Experimental
description: Twelve patients with cerebral vasospasm following aneurysmal subarachnoid hemorrhage will be assigned to low dose sildenafil citrate and will receive a 20mg oral dose and a subsequent 10mg intravenous dose of sildenafil citrate.
arm group label: High dose sildenafil
arm group type: Experimental
description: Twelve patients with cerebral vasospasm following aneurysmal subarachnoid hemorrhage will be assigned to high dose sildenafil citrate and will receive a 60mg oral dose and a subsequent 30mg intravenous dose of sildenafil citrate.
intervention type: Drug
intervention name: Low dose sildenafil citrate
arm group label: Low dose sildenafil
intervention type: Drug
intervention name: High dose sildenafil citrate
arm group label: High dose sildenafil
criteria: 
gender: All
minimum age: 21 Years
maximum age: N/A
healthy volunteers: No
last name: Chad W Washington, MS, MD, MPHS
role: Principal Investigator
affiliation: University of Mississippi Medical Center
facility: 
country: United States
citation: Washington CW, Derdeyn CP, Dhar R, Arias EJ, Chicoine MR, Cross DT, Dacey RG Jr, Han BH, Moran CJ, Rich KM, Vellimana AK, Zipfel GJ. A Phase I proof-of-concept and safety trial of sildenafil to treat cerebral vasospasm following subarachnoid hemorrhage. J Neurosurg. 2016 Feb;124(2):318-27. doi: 10.3171/2015.2.JNS142752. Epub 2015 Aug 28.
PMID: 26314998
citation: Dhar R, Washington C, Diringer M, Zazulia A, Jafri H, Derdeyn C, Zipfel G. Acute Effect of Intravenous Sildenafil on Cerebral Blood Flow in Patients with Vasospasm After Subarachnoid Hemorrhage. Neurocrit Care. 2016 Oct;25(2):201-4. doi: 10.1007/s12028-016-0243-0.
PMID: 26940913
responsible party type: Sponsor
mesh term: Subarachnoid Hemorrhage
mesh term: Vasospasm, Intracranial
mesh term: Hemorrhage
mesh term: Sildenafil Citrate
mesh term: Citric Acid
mesh term: Sodium Citrate
sharing ipd: No