xml: <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/NCT06032533</url>
    </required_header>
    <id_info>
      <org_study_id>1-16-02-429-22</org_study_id>
      <secondary_id>787394</secondary_id>
      <secondary_id>2304824</secondary_id>
      <nct_id>NCT06032533</nct_id>
    </id_info>
    <brief_title>Remote Ischemic Conditioning in Aneurysmal SAH: a Randomized, Patient-assessor Blinded, Sham-controlled Study.</brief_title>
    <acronym>RESCUE-SAH</acronym>
    <official_title>The Effect of Remote Ischemic Conditioning on Delayed Cerebral Ischemia in Aneurysmal Subarachnoid Hemorrhage: A Prospective, Randomized, Patient-assessor Blinded, Sham-controlled Pilot Study Investigating Effect on Clinical Outcome.</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Aarhus University Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Aarhus University Hospital</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The goal of this clinical trial is to examine the effect of limb occlusion therapy (remote&#xD;
        ischemic conditioning, RIC) in subjects with aneurysmal subarachnoid hemorrhage.&#xD;
  &#xD;
        The main question it aims to answer is whether RIC can improve long-term recovery in&#xD;
        participants with aneurysmal subarachnoid hemorrhage.&#xD;
  &#xD;
        Researchers will compare levels of functional independence in participants in the RIC-group&#xD;
        to participants in the sham-group.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Aneurysmal subarachnoid hemorrhage (aSAH) is one of the most devastating types of stroke.&#xD;
        Half of the patients die during the acute ictus, and those who survive have a poor prognosis&#xD;
        as 20-30% are disabled or eventually die from the disease. In the acute phase after aSAH, the&#xD;
        most devastating complication is rebleeding, whereas in the late phase, delayed cerebral&#xD;
        ischemia (DCI) is another feared complication, associated with high morbidity and mortality.&#xD;
        Symptoms of DCI occur in 30 % of patients and 15-20 % of patients will develop a disabling&#xD;
        stroke due to DCI. DCI typically occurs between days 4 and 14 after the initial bleeding. The&#xD;
        cause of DCI is not fully understood. Cerebral vasospasms (CVS) are commonly seen on&#xD;
        angiography in the first 4-14 days after initial bleeding, and have been linked to late onset&#xD;
        of symptoms of focal ischaemia since the 60s. Modern research suggests that the&#xD;
        pathophysiology is multifactorial, but CVS is still thought to be a major contributor. Other&#xD;
        contributing factors are thought to be microthrombosis, microvascular spasm, oxidative&#xD;
        stress, cortically spreading depolarizations, cell death, breakdown of blood-brain barrier,&#xD;
        among others. Treatment with nimodipine is standard-of-care and is the only pharmacological&#xD;
        intervention that has been shown to improve outcome in aSAH patients, although it has no&#xD;
        impact on large-vessel CVS[.&#xD;
  &#xD;
        The need for developing effective methods for prevention or treatment of DCI persists, and an&#xD;
        effective prophylactic treatment may have a large impact on the general outcome of aSAH.&#xD;
  &#xD;
        Ischemic conditioning is a potent activator of endogenous protection against ischemic injury.&#xD;
        RIC can be applied as repeated short-lasting ischemia in a distant tissue that results in&#xD;
        protection against subsequent long-lasting ischemic injury in the target organ. This&#xD;
        protection can be applied prior to or during a prolonged ischemic event as remote ischemic&#xD;
        preconditioning (RIPreC) and perconditioning (RIPerC), respectively.&#xD;
  &#xD;
        RIC is commonly achieved by inflation of a blood pressure cuff to induce 5-minute cycles of&#xD;
        limb ischemia alternating with 5 minutes of reperfusion. RIC activates several protective&#xD;
        mechanisms, through humoral and neural pathways and shows promise in the setting of acute&#xD;
        stroke.&#xD;
  &#xD;
        Inflammation initiated by cerebral ischemia can contribute to secondary brain injury and is&#xD;
        correlated with poor outcome. Following ischemia there is a harmful excess leukocyte&#xD;
        infiltration in the brain parenchyma, and in experimental studies on aSAH, pharmacological&#xD;
        inhibition of cytokines has been associated with improved outcome. RIC has been demonstrated&#xD;
        to reduce inflammation and downregulate inflammatory markers. In addition, RIC has protective&#xD;
        effects on cerebral endothelial function and induces vasodilation, increasing cerebral blood&#xD;
        flow (CBF).&#xD;
  &#xD;
        Angiogenesis, erythropoietin and nitric oxide (NO) are suggested to induce neuroprotection&#xD;
        and stimulation of these strategies by conditioning including inhibition of inflammation has&#xD;
        the potential to play an important part in treatment of patients after aSAH.&#xD;
  &#xD;
        The effect of RIC on blood and cerebrospinal fluid biomarkers has never been explored in the&#xD;
        setting of aSAH.&#xD;
  &#xD;
        To-date, no serious adverse events have been documented in RIC. The procedure has been&#xD;
        applied in numerous cardiovascular ischemic patients and in patients suffering from ischemic&#xD;
        stroke and cerebral hemorrhage (ICH/SAH).&#xD;
  &#xD;
        A recent smaller randomized trials of RIPreC after aSAH showed promising results with regards&#xD;
        to functional outcomes and incidence of cerebral oxygen desaturation, likewise without&#xD;
        adverse effects of RIC.&#xD;
  &#xD;
        RIC is a non-pharmacologic and non-invasive treatment without noticeable discomfort that has&#xD;
        neuroprotective potential worldwide.&#xD;
  &#xD;
        Aneurysmal SAH and subsequent DCI represents a unique clinical opportunity to test RIC as DCI&#xD;
        typically manifests within the first 14 days after ictus and is often a significant&#xD;
        contributor to neurological injury. The treatment is feasible, safe, and rooted in&#xD;
        well-explored physiological concepts. There is a clear scientific gap and opportunity to&#xD;
        explore RIC in the setting of aSAH and DCI in larger randomized trials.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">November 30, 2027</completion_date>
    <primary_completion_date type="Anticipated">November 30, 2027</primary_completion_date>
    <phase>N/A</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>Participants are randomized to either daily treatment with remote ischemic conditioning or daily sham-treatment.</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Double (Participant, Outcomes Assessor)</masking>
      <masking_description>Outcomes assessors are recruited from another department, and have not been involved with subjects prior to the telephone interview. Participants and outcome assessors are blinded to subject intervention.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Clinical outcome after 6 months measured by modified Rankin scale</measure>
      <time_frame>Assessed 6 months after initial aneurysm rupture.</time_frame>
      <description>Assessed by telephone interview. Patient assessor is blinded to intervention</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Difference in Infarct growth</measure>
      <time_frame>MRI performed 4-6 weeks after initial hemorrhage.</time_frame>
      <description>Assessed by MRI, measured by segmentation and calculation of infarct volume.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Clinical outcome after 14 days measured by modified Rankin scale.</measure>
      <time_frame>14 days after initial hemorrhage.</time_frame>
      <description>Assessed by clinician in charge of patient discharge.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Occurrence of delayed cerebral ischemia</measure>
      <time_frame>Within first 14 days after initial hemorrhage.</time_frame>
      <description>Neurological deterioration after aSAH where DCI is deemed most likely cause, supported by angiography/perfusion CT.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Mortality after 3 months</measure>
      <time_frame>Assessed at 3 months post initial hemorrhage</time_frame>
      <description>Assessed via patient records. Assessor is blinded to intervention.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Mortality after 12 months</measure>
      <time_frame>Assessed at 12 months post initial hemorrhage</time_frame>
      <description>Assessed via patient records. Assessor is blinded to the intervention.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Presence of angiographic vasospasm on CT angiography baseline vs 8-day scan</measure>
      <time_frame>8-9 days post initial hemorrhage.</time_frame>
      <description>Evaluated by a neuro-radiologist with more than 10 years of experience in intracerebral angiography. Assessor is blinded to intervention.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">100</enrollment>
    <condition>Subarachnoid Hemorrhage, Aneurysmal</condition>
    <condition>Delayed Cerebral Ischemia</condition>
    <arm_group>
      <arm_group_label>Remote Ischemic Conditioning</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>After randomization a large thigh blood pressure cuff will be placed on the lower limb. The cuff will be inflated to a pressure 30 mm Hg greater than the systolic arterial blood pressure measured by the patient's arterial line or upper limb blood pressure cuff. The adequate level of inflation will be confirmed by the absence of pulse in the ipsilateral pedal artery detected by palpation. If the pulse signal is still present, the cuff will be inflated further until it disappears. The cuff will remain inflated for 5 minutes. Then the cuff will be deflated and the limb allowed to re-perfuse for 5 minutes. The procedure will be repeated five times followed by reperfusion. The first session will be performed 24-72 hours after the initial hemorrhage, within the first 24 hours after treatment of aneurysm, and repeated every 24 hours, between 8-10 am, until post hemorrhagic day 14.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Sham-RIC</arm_group_label>
      <arm_group_type>Sham Comparator</arm_group_type>
      <description>After randomization a large leg blood pressure cuff will be placed on the lower limb. This cuff is not attached to the device, but appears to be. The device will the be operated by trained staff. A hidden cuff is attached to the device to ensure that the device produces regular operation noises. The hidden cuff (not attached to patient) is inflated. The cuff will remain inflated for 5 minutes, then the cuff will be deflated for 5 minutes. The procedure will be repeated for five cycles. The first session will be performed 48-72 hours after the initial hemorrhage, at least 24 hours after treatment of aneurysm and repeated every 24 hours, between 8-10 am, until post hemorrhagic day 14.</description>
    </arm_group>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>Remote Ischemic Conditioning with Automatic Tourniquet Device</intervention_name>
      <description>5 Cycles of Remote Ischemic Conditioning performed on the leg. One cycle consists of 5 minutes of arterial occlusion followed by 5 minutes of reperfusion. The above is repeated daily for 14 days or until patient is discharged.&#xD;
  Patients are randomized to either active Remote Ischemic Conditioning or Sham-treatment.</description>
      <arm_group_label>Remote Ischemic Conditioning</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>Sham Remote Ischemic Conditioning with Automatic Tourniquet Device</intervention_name>
      <description>5 Cycles of sham-treatment performed on the leg. One cycle consists of 5 minutes of sham-treatment followed by 5 minutes of pause. The above is repeated daily for 14 days or until patient is discharged.&#xD;
  Patients are randomized to either active Remote Ischemic Conditioning or Sham-treatment.</description>
      <arm_group_label>Sham-RIC</arm_group_label>
      <other_name>Sham</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Aneurysmal subarachnoid hemorrhage confirmed by computed tomography (CT) with aneurysm&#xD;
               origin confirmed by computed tomography angiography (CTA) or digital subtraction&#xD;
               angiography (DSA)&#xD;
  &#xD;
            -  Aneurysmal subarachnoid hemorrhage symptom-onset ≤ 3 days&#xD;
  &#xD;
            -  Aneurysm protected by clipping or coiling&#xD;
  &#xD;
            -  Independent in daily living before symptom onset (mRS ≤ 2)&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Subarachnoid hemorrhage caused by a lesion other than cerebral aneurysm&#xD;
  &#xD;
            -  Symptomatic vasospasm at the time of enrollment&#xD;
  &#xD;
            -  Previous cerebral lesion e.g. symptomatic cerebral infarction (&gt;2cm), multiple&#xD;
               sclerosis, symptomatic intracerebral hemorrhage, tumour, prior neurosurgery (excluding&#xD;
               prior clipping or coiling of cold aneurysms without complications).&#xD;
  &#xD;
            -  History of severe peripheral vascular disease or signs of severe peripheral vascular&#xD;
               disease on physical examination&#xD;
  &#xD;
            -  History of deep vein thrombosis or signs of deep vein thrombosis on physical&#xD;
               examination&#xD;
  &#xD;
            -  Kidney involvement or prior kidney disease with an estimated glomerular filtration&#xD;
               rate (eGFR) below safe levels for contrast infusion in relation to CT-perfusion.&#xD;
  &#xD;
            -  Pregnancy (Women of child-bearing age will have serum-Humane Choriogonadotropine taken&#xD;
               prior to final inclusion. If pregnancy cannot be ruled out,the patient can't be&#xD;
               included. Women with a safe birth control method will be encouraged to use this method&#xD;
               during the entire period of active treatment.)&#xD;
  &#xD;
            -  Concomitant other acute life-threatening medical or surgical condition&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Grethe Andersen, Prof., MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Department of Neurology, Aarhus University Hospital</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Arzu Bilgin-Freiert, MD, PhD</last_name>
      <role>Study Director</role>
      <affiliation>Department of Neurosurgery</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Kim M Ørskov, MD</last_name>
      <phone>+4542791933</phone>
      <email>kimoer@rm.dk</email>
    </overall_contact>
    <location>
      <facility>
        <name>Department of Neurosurgery, Aarhus University Hospital</name>
        <address>
          <city>Aarhus N</city>
          <state>Danmark</state>
          <zip>DK-8200</zip>
          <country>Denmark</country>
        </address>
      </facility>
      <contact>
        <last_name>Jens Christian H Sørensen, Prof., MD</last_name>
      </contact>
      <contact_backup>
        <last_name>Arzu Bilgin-Freiert, MD, PhD</last_name>
        <phone>+4529474197</phone>
        <email>arzbil@rm.dk</email>
      </contact_backup>
      <investigator>
        <last_name>Kim M Ørskov, MD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>Denmark</country>
    </location_countries>
    <link>
      <url>https://www.uptodate.com/contents/aneurysmal-subarachnoid-hemorrhage-treatment-and-prognosis</url>
      <description>Background on Aneurysmal Subarachnoid Hemorrhage and Delayed Cerebral Ischemia</description>
    </link>
    <reference>
      <citation>Hess DC, Blauenfeldt RA, Andersen G, Hougaard KD, Hoda MN, Ding Y, Ji X. Remote ischaemic conditioning-a new paradigm of self-protection in the brain. Nat Rev Neurol. 2015 Dec;11(12):698-710. doi: 10.1038/nrneurol.2015.223. Epub 2015 Nov 20.</citation>
      <PMID>26585977</PMID>
    </reference>
    <reference>
      <citation>Gonzalez NR, Connolly M, Dusick JR, Bhakta H, Vespa P. Phase I clinical trial for the feasibility and safety of remote ischemic conditioning for aneurysmal subarachnoid hemorrhage. Neurosurgery. 2014 Nov;75(5):590-8; discussion 598. doi: 10.1227/NEU.0000000000000514.</citation>
      <PMID>25072112</PMID>
    </reference>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>September 5, 2023</study_first_submitted>
    <study_first_submitted_qc>September 5, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 13, 2023</study_first_posted>
    <last_update_submitted>September 5, 2023</last_update_submitted>
    <last_update_submitted_qc>September 5, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 13, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Aarhus University Hospital</investigator_affiliation>
      <investigator_full_name>Grethe Andersen</investigator_full_name>
      <investigator_title>Professor, Consultant Neurologist, MD</investigator_title>
    </responsible_party>
    <keyword>Remote Ischemic Conditioning</keyword>
    <keyword>Subarachnoid Hemorrhage</keyword>
    <keyword>Aneurysm</keyword>
    <keyword>Delayed Cerebral Ischemia</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Subarachnoid Hemorrhage</mesh_term>
      <mesh_term>Brain Ischemia</mesh_term>
      <mesh_term>Cerebral Infarction</mesh_term>
      <mesh_term>Ischemia</mesh_term>
      <mesh_term>Hemorrhage</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>Individual participant data that underlie the results reported in this article after de-identification of participants</ipd_description>
      <ipd_info_type>Study Protocol</ipd_info_type>
      <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
      <ipd_info_type>Analytic Code</ipd_info_type>
      <ipd_time_frame>Beginning 3 moths and ending 5 years following publication of results</ipd_time_frame>
      <ipd_access_criteria>Proposals should be directed to kimoer@rm.dk. To gain access data requestors will need to sign a data processing agreement.</ipd_access_criteria>
    </patient_data>
    <provided_document_section>
      <provided_document>
        <document_type>Study Protocol and Statistical Analysis Plan</document_type>
        <document_has_protocol>Yes</document_has_protocol>
        <document_has_icf>No</document_has_icf>
        <document_has_sap>Yes</document_has_sap>
        <document_date>June 21, 2023</document_date>
        <document_url>https://ClinicalTrials.gov/ProvidedDocs/33/NCT06032533/Prot_SAP_000.pdf</document_url>
      </provided_document>
    </provided_document_section>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06032533
  org study id: 1-16-02-429-22
  secondary id: 787394
  secondary id: 2304824
  nct id: NCT06032533
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The goal of this clinical trial is to examine the effect of limb occlusion therapy (remote
        ischemic conditioning, RIC) in subjects with aneurysmal subarachnoid hemorrhage.
  
        The main question it aims to answer is whether RIC can improve long-term recovery in
        participants with aneurysmal subarachnoid hemorrhage.
  
        Researchers will compare levels of functional independence in participants in the RIC-group
        to participants in the sham-group.
  Aneurysmal subarachnoid hemorrhage (aSAH) is one of the most devastating types of stroke.
        Half of the patients die during the acute ictus, and those who survive have a poor prognosis
        as 20-30% are disabled or eventually die from the disease. In the acute phase after aSAH, the
        most devastating complication is rebleeding, whereas in the late phase, delayed cerebral
        ischemia (DCI) is another feared complication, associated with high morbidity and mortality.
        Symptoms of DCI occur in 30 % of patients and 15-20 % of patients will develop a disabling
        stroke due to DCI. DCI typically occurs between days 4 and 14 after the initial bleeding. The
        cause of DCI is not fully understood. Cerebral vasospasms (CVS) are commonly seen on
        angiography in the first 4-14 days after initial bleeding, and have been linked to late onset
        of symptoms of focal ischaemia since the 60s. Modern research suggests that the
        pathophysiology is multifactorial, but CVS is still thought to be a major contributor. Other
        contributing factors are thought to be microthrombosis, microvascular spasm, oxidative
        stress, cortically spreading depolarizations, cell death, breakdown of blood-brain barrier,
        among others. Treatment with nimodipine is standard-of-care and is the only pharmacological
        intervention that has been shown to improve outcome in aSAH patients, although it has no
        impact on large-vessel CVS[.
  
        The need for developing effective methods for prevention or treatment of DCI persists, and an
        effective prophylactic treatment may have a large impact on the general outcome of aSAH.
  
        Ischemic conditioning is a potent activator of endogenous protection against ischemic injury.
        RIC can be applied as repeated short-lasting ischemia in a distant tissue that results in
        protection against subsequent long-lasting ischemic injury in the target organ. This
        protection can be applied prior to or during a prolonged ischemic event as remote ischemic
        preconditioning (RIPreC) and perconditioning (RIPerC), respectively.
  
        RIC is commonly achieved by inflation of a blood pressure cuff to induce 5-minute cycles of
        limb ischemia alternating with 5 minutes of reperfusion. RIC activates several protective
        mechanisms, through humoral and neural pathways and shows promise in the setting of acute
        stroke.
  
        Inflammation initiated by cerebral ischemia can contribute to secondary brain injury and is
        correlated with poor outcome. Following ischemia there is a harmful excess leukocyte
        infiltration in the brain parenchyma, and in experimental studies on aSAH, pharmacological
        inhibition of cytokines has been associated with improved outcome. RIC has been demonstrated
        to reduce inflammation and downregulate inflammatory markers. In addition, RIC has protective
        effects on cerebral endothelial function and induces vasodilation, increasing cerebral blood
        flow (CBF).
  
        Angiogenesis, erythropoietin and nitric oxide (NO) are suggested to induce neuroprotection
        and stimulation of these strategies by conditioning including inhibition of inflammation has
        the potential to play an important part in treatment of patients after aSAH.
  
        The effect of RIC on blood and cerebrospinal fluid biomarkers has never been explored in the
        setting of aSAH.
  
        To-date, no serious adverse events have been documented in RIC. The procedure has been
        applied in numerous cardiovascular ischemic patients and in patients suffering from ischemic
        stroke and cerebral hemorrhage (ICH/SAH).
  
        A recent smaller randomized trials of RIPreC after aSAH showed promising results with regards
        to functional outcomes and incidence of cerebral oxygen desaturation, likewise without
        adverse effects of RIC.
  
        RIC is a non-pharmacologic and non-invasive treatment without noticeable discomfort that has
        neuroprotective potential worldwide.
  
        Aneurysmal SAH and subsequent DCI represents a unique clinical opportunity to test RIC as DCI
        typically manifests within the first 14 days after ictus and is often a significant
        contributor to neurological injury. The treatment is feasible, safe, and rooted in
        well-explored physiological concepts. There is a clear scientific gap and opportunity to
        explore RIC in the setting of aSAH and DCI in larger randomized trials.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: Participants are randomized to either daily treatment with remote ischemic conditioning or daily sham-treatment.
  primary purpose: Treatment
  masking: Double (Participant, Outcomes Assessor)
  masking description: Outcomes assessors are recruited from another department, and have not been involved with subjects prior to the telephone interview. Participants and outcome assessors are blinded to subject intervention.
  measure: Clinical outcome after 6 months measured by modified Rankin scale
  time frame: Assessed 6 months after initial aneurysm rupture.
  description: Assessed by telephone interview. Patient assessor is blinded to intervention
  measure: Difference in Infarct growth
  time frame: MRI performed 4-6 weeks after initial hemorrhage.
  description: Assessed by MRI, measured by segmentation and calculation of infarct volume.
  measure: Clinical outcome after 14 days measured by modified Rankin scale.
  time frame: 14 days after initial hemorrhage.
  description: Assessed by clinician in charge of patient discharge.
  measure: Occurrence of delayed cerebral ischemia
  time frame: Within first 14 days after initial hemorrhage.
  description: Neurological deterioration after aSAH where DCI is deemed most likely cause, supported by angiography/perfusion CT.
  measure: Mortality after 3 months
  time frame: Assessed at 3 months post initial hemorrhage
  description: Assessed via patient records. Assessor is blinded to intervention.
  measure: Mortality after 12 months
  time frame: Assessed at 12 months post initial hemorrhage
  description: Assessed via patient records. Assessor is blinded to the intervention.
  measure: Presence of angiographic vasospasm on CT angiography baseline vs 8-day scan
  time frame: 8-9 days post initial hemorrhage.
  description: Evaluated by a neuro-radiologist with more than 10 years of experience in intracerebral angiography. Assessor is blinded to intervention.
  arm group label: Remote Ischemic Conditioning
  arm group type: Experimental
  description: After randomization a large thigh blood pressure cuff will be placed on the lower limb. The cuff will be inflated to a pressure 30 mm Hg greater than the systolic arterial blood pressure measured by the patient's arterial line or upper limb blood pressure cuff. The adequate level of inflation will be confirmed by the absence of pulse in the ipsilateral pedal artery detected by palpation. If the pulse signal is still present, the cuff will be inflated further until it disappears. The cuff will remain inflated for 5 minutes. Then the cuff will be deflated and the limb allowed to re-perfuse for 5 minutes. The procedure will be repeated five times followed by reperfusion. The first session will be performed 24-72 hours after the initial hemorrhage, within the first 24 hours after treatment of aneurysm, and repeated every 24 hours, between 8-10 am, until post hemorrhagic day 14.
  arm group label: Sham-RIC
  arm group type: Sham Comparator
  description: After randomization a large leg blood pressure cuff will be placed on the lower limb. This cuff is not attached to the device, but appears to be. The device will the be operated by trained staff. A hidden cuff is attached to the device to ensure that the device produces regular operation noises. The hidden cuff (not attached to patient) is inflated. The cuff will remain inflated for 5 minutes, then the cuff will be deflated for 5 minutes. The procedure will be repeated for five cycles. The first session will be performed 48-72 hours after the initial hemorrhage, at least 24 hours after treatment of aneurysm and repeated every 24 hours, between 8-10 am, until post hemorrhagic day 14.
  intervention type: Device
  intervention name: Remote Ischemic Conditioning with Automatic Tourniquet Device
  description: 5 Cycles of Remote Ischemic Conditioning performed on the leg. One cycle consists of 5 minutes of arterial occlusion followed by 5 minutes of reperfusion. The above is repeated daily for 14 days or until patient is discharged.
  Patients are randomized to either active Remote Ischemic Conditioning or Sham-treatment.
  arm group label: Remote Ischemic Conditioning
  intervention type: Device
  intervention name: Sham Remote Ischemic Conditioning with Automatic Tourniquet Device
  description: 5 Cycles of sham-treatment performed on the leg. One cycle consists of 5 minutes of sham-treatment followed by 5 minutes of pause. The above is repeated daily for 14 days or until patient is discharged.
  Patients are randomized to either active Remote Ischemic Conditioning or Sham-treatment.
  arm group label: Sham-RIC
  other name: Sham
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Grethe Andersen, Prof., MD
  role: Principal Investigator
  affiliation: Department of Neurology, Aarhus University Hospital
  last name: Arzu Bilgin-Freiert, MD, PhD
  role: Study Director
  affiliation: Department of Neurosurgery
  last name: Kim M Ørskov, MD
  phone: +4542791933
  email: kimoer@rm.dk
  facility: 
  contact: 
  contact backup: 
  investigator: 
  country: Denmark
  url: https://www.uptodate.com/contents/aneurysmal-subarachnoid-hemorrhage-treatment-and-prognosis
  description: Background on Aneurysmal Subarachnoid Hemorrhage and Delayed Cerebral Ischemia
  citation: Hess DC, Blauenfeldt RA, Andersen G, Hougaard KD, Hoda MN, Ding Y, Ji X. Remote ischaemic conditioning-a new paradigm of self-protection in the brain. Nat Rev Neurol. 2015 Dec;11(12):698-710. doi: 10.1038/nrneurol.2015.223. Epub 2015 Nov 20.
  PMID: 26585977
  citation: Gonzalez NR, Connolly M, Dusick JR, Bhakta H, Vespa P. Phase I clinical trial for the feasibility and safety of remote ischemic conditioning for aneurysmal subarachnoid hemorrhage. Neurosurgery. 2014 Nov;75(5):590-8; discussion 598. doi: 10.1227/NEU.0000000000000514.
  PMID: 25072112
  responsible party type: Principal Investigator
  investigator affiliation: Aarhus University Hospital
  investigator full name: Grethe Andersen
  investigator title: Professor, Consultant Neurologist, MD
  mesh term: Subarachnoid Hemorrhage
  mesh term: Brain Ischemia
  mesh term: Cerebral Infarction
  mesh term: Ischemia
  mesh term: Hemorrhage
  sharing ipd: Yes
  ipd description: Individual participant data that underlie the results reported in this article after de-identification of participants
  ipd info type: Study Protocol
  ipd info type: Statistical Analysis Plan (SAP)
  ipd info type: Analytic Code
  ipd time frame: Beginning 3 moths and ending 5 years following publication of results
  ipd access criteria: Proposals should be directed to kimoer@rm.dk. To gain access data requestors will need to sign a data processing agreement.
  provided document: 