<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/NCT03754335</url>
  </required_header>
  <id_info>
    <org_study_id>RC31/17/0355</org_study_id>
    <secondary_id>2018-A00629-46</secondary_id>
    <nct_id>NCT03754335</nct_id>
  </id_info>
  <brief_title>SubArachnoid Hemorrhage HEadache Treated by Lumbar Puncture</brief_title>
  <acronym>SAH-HELP</acronym>
  <official_title>SubArachnoid Hemorrhage HEadache Treated by Lumbar Puncture</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Toulouse</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Toulouse</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>
      Headache control is one of the major challenges in patients who suffered an acute aneurysmal&#xD;
      subarachnoid hemorrhage (aSAH). Headache affects 90% of the patient and is resistant to the&#xD;
      major pain medication. It results from the increased intracranial pressure and the&#xD;
      inflammation caused by the accumulation of arterial blood in the subarachnoid space.&#xD;
      Hemorrhagic cerebrospinal fluid (CSF) removal by a lumbar puncture (LP), is well tolerated,&#xD;
      reduces intracranial pressure and accelerates the clearance of the blood products from CSF.&#xD;
      Nonetheless it has never been tested in a randomized trial. The investigators aim to compare&#xD;
      in patients who experienced a low grade aSAH, the variation of headache intensity after CSF&#xD;
      removal by LP vs. Sham LP in addition to predefined analgesic protocol management.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      After aneurysmal subarachnoid hemorrhage (aSAH) almost 90 % of patients experience a severe&#xD;
      headache during their hospital stay. Pain control often requires high doses of opioid drugs&#xD;
      and sedation that remain only partially efficacious. In addition, there is to the&#xD;
      investigator's knowledge currently no recommendation or consensus on aSAH related headache&#xD;
      management. aSAH related headache results from the prolonged increased intracranial pressure&#xD;
      and meningeal inflammation related to the accumulation of blood products in the subarachnoid&#xD;
      space. Preliminary studies, suggest that hemorrhagic cerebrospinal fluid (CSF) removal by&#xD;
      lumbar puncture (LP) or lumbar drain, is safe and decreases intracranial pressure. However&#xD;
      its impact on headache control has never been tested. A reliable headache evaluation has to&#xD;
      be performed among conscious patients experiencing a &quot;low-grade&quot; aSAH.&#xD;
&#xD;
      The objective of the study is to evaluate in patients experiencing low-grade acute aSAH (WFNS&#xD;
      1-3), the efficacy of CSF removal by LP vs. sham LP, on headache control. 74 patients with&#xD;
      secured aneurysm by coiling, will be randomized (1:1) between day 3 and day 5 after&#xD;
      aneurysmal rupture. The procedure will be performed in addition to a pre-specified antalgic&#xD;
      protocol.&#xD;
&#xD;
      Mean headache intensity will be measured with the numeric verbal scale during the 24 hours&#xD;
      before and the 24 hours after the procedure. The variation of mean intensity will be compared&#xD;
      between the 2 groups.&#xD;
&#xD;
      The investigators hypothesize that this treatment may significantly decrease headache&#xD;
      intensity after an aSAH. If this hypothesis is confirmed CSF removal by LP could be a simple&#xD;
      cost effective and worldwide available strategy to improve&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 28, 2018</start_date>
  <completion_date type="Actual">December 1, 2022</completion_date>
  <primary_completion_date type="Actual">December 1, 2022</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>Randomized, double blind, prospective monocentric trial evaluating in parallel groups</intervention_model_description>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
    <masking_description>This procedure is to be able to easily randomize half of the patients into a &quot;sham&quot; LP arm passed by independent practitioners of the investigators in charge of the patient, which allows a good double-blind study.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Difference of headache mean intensity variation measured after a lumbar puncture or a sham LP.</measure>
    <time_frame>24 hours after the inclusion</time_frame>
    <description>The mean intensity will be assessed using the verbal rating scales (VRS). It is a scale administered by the medical team, which brings together the score given by the patient between 0 and 10 (0 = absence of pain; 10 = maximum of conceivable pain)Headache mean intensity variation will be calculated by the difference between these scores evaluated 24 hours before and the 24 hours after the procedure.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Difference of variation in the mean intensity of headache</measure>
    <time_frame>48 hours</time_frame>
    <description>Difference of variation in the mean intensity of headache measured by the nurse in charge of the patients every 4 h between the 24 hours before and the 24 hours after the procedure. Difference of variation will be assessed using the verbal rating scales (VRS). It is a scale administered by the medical team, which brings together the score given by the patient between 0 and 10 (0 = absence of pain; 10 = maximum of conceivable pain). Headache mean intensity variation will be calculated by the difference between these scores evaluated 24 hours before and the 24 hours after the procedure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference of maximal headache intensity</measure>
    <time_frame>48 hours</time_frame>
    <description>Difference of maximal headache intensity will be assessed using the verbal rating scales (VRS). It is a scale administered by the medical team, which brings together the score given by the patient between 0 and 10 (0 = absence of pain; 10 = maximum of conceivable pain). Headache maximal intensity variation will be calculated by the difference of maximal headache intensity measured during 24 hours before and 24 hours after the procedure by the nurse in charge of the patients every 4 hours.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Kinetic of headache intensity</measure>
    <time_frame>7 days</time_frame>
    <description>Kinetic of headache intensity during the 7 days following the procedure (global assesment by the patient and mean/max of measurement every 4 hours). The headache intensity will be assessed using the verbal rating scales (VRS). It is a scale administered by the medical team, which brings together the score given by the patient between 0 and 10 (0 = absence of pain; 10 = maximum of conceivable pain).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference of responding patients</measure>
    <time_frame>7 days</time_frame>
    <description>Difference of responding patients defined by patients with a decreased of the mean intensity of 30 % and 50 %, 24 hours after the procedure and daily during the 7 days following the procedure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of a clinical deterioration</measure>
    <time_frame>1 day</time_frame>
    <description>Related to the other complication of subarachnoid hemorrhage : Occurrence of a clinical deterioration related to delayed cerebral ischemia assessed by NIHSS and GCS) and the occurrence of a new infarction on follow-up MRI.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Persistence of Chronic hydrocephalus</measure>
    <time_frame>3 month</time_frame>
    <description>Rate of chronic hydrocephalus defined by the modification of the ventricle size between the post interventional MRI and the follow-up MRI at 3 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Improvement of the clinical global impression</measure>
    <time_frame>3 months</time_frame>
    <description>Disability and Quality of life : Improvement of the &quot;Clinical Global Impression -Improvement&quot; (CGI-I) at 24 hours, day 7 and 3 months (clinical improvement defined by a score of 1 or 2). The CGI-I is used by clinicians to rate improvement in a subject's condition (benefits) since baseline. It is a 7-point scale with 1=very much improved, 2=much improved, 3=minimally improved, 4=not changed, 5=minimally worse, 6=much worse; and 7=very much worse.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">74</enrollment>
  <condition>Aneurysmal Subarachnoid Hemorrhage</condition>
  <condition>Headache</condition>
  <arm_group>
    <arm_group_label>Lumbar puncture</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Lumbar puncture in addition to a predefined analgesic protocol Patients will be randomized between the 3rd and 5th days following aneurismal rupture.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham lumbar puncture</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Sham lumbar puncture in addition to a predefined analgesic protocol Patients will be randomized between the 3rd and 5th days following aneurismal rupture.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Lumbar puncture</intervention_name>
    <description>Patient will be managed according to the current international recommendations in the Toulouse acute stroke center.&#xD;
In the absence of clear recommendation in the literature headache will be treated according to our local predefined analgesic protocol: paracetamol 1g/6 h, and if the numerical scale ≥ 4 : continuous intravenous morphine starting at 1mg/h and increased per 0.5 mg/h every hour if numerical scale remains ≥ 4.&#xD;
Lumbar puncture will be performed between day 3 and day 5 after subarachnoid hemorrhage onset by an independent scientist from our clinical investigator center. 30-mL CSF will be removed by LP.&#xD;
Sham LP consisting in superficial skin puncture by a subcutaneous needle (27 gauge needle) during the usual procedure will be performed at the same time point.</description>
    <arm_group_label>Lumbar puncture</arm_group_label>
    <arm_group_label>Sham lumbar puncture</arm_group_label>
    <other_name>Sham Lumbar Puncture</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age &gt;18 years&#xD;
&#xD;
          -  Low grade subarachnoid hemorrhage (WFNS score between 1 and 3)&#xD;
&#xD;
          -  Aneurysmal rupture ≤ 5 days&#xD;
&#xD;
          -  Ruptured aneurysm secured by coiling since at least 48 h&#xD;
&#xD;
          -  Headache with a mean numeric verbal scale ≥ 4/10 during the last 24 hours&#xD;
&#xD;
          -  No contraindication for lumbar puncture&#xD;
&#xD;
          -  Affiliation to french social security&#xD;
&#xD;
          -  Person able to express her consent and to assess own headache intensity&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Minor,&#xD;
&#xD;
          -  Pregnancy, breastfeeding&#xD;
&#xD;
          -  Subarachnoid hemorrhage without aneurysm&#xD;
&#xD;
          -  Ruptured aneurysm not secured&#xD;
&#xD;
          -  High grade (WFNS 4 and 5) subarachnoid hemorrhage&#xD;
&#xD;
          -  Efficient anticoagulation&#xD;
&#xD;
          -  External ventricular drain placed before randomisation&#xD;
&#xD;
          -  People under legal protection&#xD;
&#xD;
          -  Participation to another research study with an ongoing disqualification period&#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>Lionel Calvière, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital, Toulouse</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospital Toulouse</name>
      <address>
        <city>Toulouse</city>
        <zip>31059</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>November 19, 2018</study_first_submitted>
  <study_first_submitted_qc>November 23, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 27, 2018</study_first_posted>
  <last_update_submitted>February 10, 2023</last_update_submitted>
  <last_update_submitted_qc>February 10, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 13, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Aneurysmal subarachnoid hemorrhage</keyword>
  <keyword>lumbar puncture</keyword>
  <keyword>headache</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Subarachnoid Hemorrhage</mesh_term>
    <mesh_term>Hemorrhage</mesh_term>
    <mesh_term>Headache</mesh_term>
  </condition_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/NCT03754335
org study id: RC31/17/0355
secondary id: 2018-A00629-46
nct id: NCT03754335
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Headache control is one of the major challenges in patients who suffered an acute aneurysmal
      subarachnoid hemorrhage (aSAH). Headache affects 90% of the patient and is resistant to the
      major pain medication. It results from the increased intracranial pressure and the
      inflammation caused by the accumulation of arterial blood in the subarachnoid space.
      Hemorrhagic cerebrospinal fluid (CSF) removal by a lumbar puncture (LP), is well tolerated,
      reduces intracranial pressure and accelerates the clearance of the blood products from CSF.
      Nonetheless it has never been tested in a randomized trial. The investigators aim to compare
      in patients who experienced a low grade aSAH, the variation of headache intensity after CSF
      removal by LP vs. Sham LP in addition to predefined analgesic protocol management.
After aneurysmal subarachnoid hemorrhage (aSAH) almost 90 % of patients experience a severe
      headache during their hospital stay. Pain control often requires high doses of opioid drugs
      and sedation that remain only partially efficacious. In addition, there is to the
      investigator's knowledge currently no recommendation or consensus on aSAH related headache
      management. aSAH related headache results from the prolonged increased intracranial pressure
      and meningeal inflammation related to the accumulation of blood products in the subarachnoid
      space. Preliminary studies, suggest that hemorrhagic cerebrospinal fluid (CSF) removal by
      lumbar puncture (LP) or lumbar drain, is safe and decreases intracranial pressure. However
      its impact on headache control has never been tested. A reliable headache evaluation has to
      be performed among conscious patients experiencing a "low-grade" aSAH.

      The objective of the study is to evaluate in patients experiencing low-grade acute aSAH (WFNS
      1-3), the efficacy of CSF removal by LP vs. sham LP, on headache control. 74 patients with
      secured aneurysm by coiling, will be randomized (1:1) between day 3 and day 5 after
      aneurysmal rupture. The procedure will be performed in addition to a pre-specified antalgic
      protocol.

      Mean headache intensity will be measured with the numeric verbal scale during the 24 hours
      before and the 24 hours after the procedure. The variation of mean intensity will be compared
      between the 2 groups.

      The investigators hypothesize that this treatment may significantly decrease headache
      intensity after an aSAH. If this hypothesis is confirmed CSF removal by LP could be a simple
      cost effective and worldwide available strategy to improve
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomized, double blind, prospective monocentric trial evaluating in parallel groups
primary purpose: Supportive Care
masking: Double (Participant, Investigator)
masking description: This procedure is to be able to easily randomize half of the patients into a "sham" LP arm passed by independent practitioners of the investigators in charge of the patient, which allows a good double-blind study.
measure: Difference of headache mean intensity variation measured after a lumbar puncture or a sham LP.
time frame: 24 hours after the inclusion
description: The mean intensity will be assessed using the verbal rating scales (VRS). It is a scale administered by the medical team, which brings together the score given by the patient between 0 and 10 (0 = absence of pain; 10 = maximum of conceivable pain)Headache mean intensity variation will be calculated by the difference between these scores evaluated 24 hours before and the 24 hours after the procedure.
measure: Difference of variation in the mean intensity of headache
time frame: 48 hours
description: Difference of variation in the mean intensity of headache measured by the nurse in charge of the patients every 4 h between the 24 hours before and the 24 hours after the procedure. Difference of variation will be assessed using the verbal rating scales (VRS). It is a scale administered by the medical team, which brings together the score given by the patient between 0 and 10 (0 = absence of pain; 10 = maximum of conceivable pain). Headache mean intensity variation will be calculated by the difference between these scores evaluated 24 hours before and the 24 hours after the procedure.
measure: Difference of maximal headache intensity
time frame: 48 hours
description: Difference of maximal headache intensity will be assessed using the verbal rating scales (VRS). It is a scale administered by the medical team, which brings together the score given by the patient between 0 and 10 (0 = absence of pain; 10 = maximum of conceivable pain). Headache maximal intensity variation will be calculated by the difference of maximal headache intensity measured during 24 hours before and 24 hours after the procedure by the nurse in charge of the patients every 4 hours.
measure: Kinetic of headache intensity
time frame: 7 days
description: Kinetic of headache intensity during the 7 days following the procedure (global assesment by the patient and mean/max of measurement every 4 hours). The headache intensity will be assessed using the verbal rating scales (VRS). It is a scale administered by the medical team, which brings together the score given by the patient between 0 and 10 (0 = absence of pain; 10 = maximum of conceivable pain).
measure: Difference of responding patients
time frame: 7 days
description: Difference of responding patients defined by patients with a decreased of the mean intensity of 30 % and 50 %, 24 hours after the procedure and daily during the 7 days following the procedure.
measure: Occurrence of a clinical deterioration
time frame: 1 day
description: Related to the other complication of subarachnoid hemorrhage : Occurrence of a clinical deterioration related to delayed cerebral ischemia assessed by NIHSS and GCS) and the occurrence of a new infarction on follow-up MRI.
measure: Persistence of Chronic hydrocephalus
time frame: 3 month
description: Rate of chronic hydrocephalus defined by the modification of the ventricle size between the post interventional MRI and the follow-up MRI at 3 months.
measure: Improvement of the clinical global impression
time frame: 3 months
description: Disability and Quality of life : Improvement of the "Clinical Global Impression -Improvement" (CGI-I) at 24 hours, day 7 and 3 months (clinical improvement defined by a score of 1 or 2). The CGI-I is used by clinicians to rate improvement in a subject's condition (benefits) since baseline. It is a 7-point scale with 1=very much improved, 2=much improved, 3=minimally improved, 4=not changed, 5=minimally worse, 6=much worse; and 7=very much worse.
arm group label: Lumbar puncture
arm group type: Experimental
description: Lumbar puncture in addition to a predefined analgesic protocol Patients will be randomized between the 3rd and 5th days following aneurismal rupture.
arm group label: Sham lumbar puncture
arm group type: Active Comparator
description: Sham lumbar puncture in addition to a predefined analgesic protocol Patients will be randomized between the 3rd and 5th days following aneurismal rupture.
intervention type: Procedure
intervention name: Lumbar puncture
description: Patient will be managed according to the current international recommendations in the Toulouse acute stroke center.
In the absence of clear recommendation in the literature headache will be treated according to our local predefined analgesic protocol: paracetamol 1g/6 h, and if the numerical scale ≥ 4 : continuous intravenous morphine starting at 1mg/h and increased per 0.5 mg/h every hour if numerical scale remains ≥ 4.
Lumbar puncture will be performed between day 3 and day 5 after subarachnoid hemorrhage onset by an independent scientist from our clinical investigator center. 30-mL CSF will be removed by LP.
Sham LP consisting in superficial skin puncture by a subcutaneous needle (27 gauge needle) during the usual procedure will be performed at the same time point.
arm group label: Lumbar puncture
arm group label: Sham lumbar puncture
other name: Sham Lumbar Puncture
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Lionel Calvière, MD
role: Principal Investigator
affiliation: University Hospital, Toulouse
facility: 
country: France
responsible party type: Sponsor
mesh term: Subarachnoid Hemorrhage
mesh term: Hemorrhage
mesh term: Headache
sharing ipd: No