<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/NCT02248233</url>
  </required_header>
  <id_info>
    <org_study_id>FengtianH-RHL-001</org_study_id>
    <nct_id>NCT02248233</nct_id>
  </id_info>
  <brief_title>Nimodipine for Treating Acute Massive Cerebral Infarction</brief_title>
  <official_title>Nimodipine for Treating Acute Massive Cerebral Infarction: a Randomized, Double-blind, Controlled Clinical Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fengtian Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Fengtian Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Massive cerebral infarction is an ischemic stroke caused by complete blockage of the internal&#xD;
      carotid artery, middle cerebral artery, or their cortical branches. The widespread&#xD;
      infarction, pathological severity and high fatality rate associated with massive cerebral&#xD;
      infarction pose a major threat to affected patients. However, there is a lack of unified&#xD;
      diagnostic criteria. Many researchers use Adams' classification, in which massive cerebral&#xD;
      infarction is diagnosed when the following criteria are met: infarct size &gt; 13 cm2; a major&#xD;
      brain-feeding artery is involved; the focal site affects more than two cerebral lobes;&#xD;
      infarct diameter line ≥ 3 cm in internal capsule of striatum.&#xD;
&#xD;
      Prolonged cerebral ischemia/reperfusion can induce complex secondary changes in brain tissue,&#xD;
      so the use of neuroprotective agents is very important. Remarkable progress has been made&#xD;
      over the last decade in understanding the protective effect of calcium antagonists against&#xD;
      cerebral ischemia. In particular, the liposoluble dihydropyridine Ca2+ antagonist nimodipine&#xD;
      selectively acts on cerebral vessels and neurons and can protect ischemic brain tissue,&#xD;
      providing a new way of treating ischemic cerebrovascular disease.&#xD;
&#xD;
      Preclinical and clinical tests have shown that nimodipine has a protective effect on ischemic&#xD;
      brain tissue, and indicate that patients should take the drug as soon as possible. However,&#xD;
      there are no reports of double-blind, randomized, controlled clinical trials addressing the&#xD;
      administration of nimodipine via intravenous drip within the time window for successful&#xD;
      treatment of acute massive cerebral infarction.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In the clinic, physicians are reluctant to use thrombolysis, Defibrase and anticoagulation&#xD;
      therapy because of the severity of symptoms, poor prognosis, risk of hemorrhage and high&#xD;
      fatality rate that occur with acute massive cerebral infarction. Nimodipine, as a selective&#xD;
      Ca2+ antagonist, is highly liposoluble, effectively crosses the blood-brain barrier,&#xD;
      selectively acts on intracranial blood vessels, and is an accepted neuroprotective agent that&#xD;
      can be applied in the clinic. The aim of the present study is to perform a double-blind,&#xD;
      randomized and controlled trial of the clinical efficacy and safety of nimodipine&#xD;
      administered as an intravenous drip in the early stages of acute massive cerebral infarction.&#xD;
&#xD;
      Patients will receive nimodipine within 3 days of infarction onset. We will closely monitor&#xD;
      the following: (1) Blood pressure and heart rate of the patient before treatment, since&#xD;
      nimodipine is contraindicated in patients with hypotension and low heart rate. Where blood&#xD;
      pressure is ≥ 100/80 mmHg and heart rate ≥ 60 BPM, nimodipine will be administered. (2) Speed&#xD;
      of infusion. This should not be too fast; we suggest 1-2 drops per minute initially,&#xD;
      increasing gradually until the drop in systolic pressure exceeds 10 mmHg. The average drip&#xD;
      speed should be 6-8 drops/minute, and the fastest drip speed 10 drops/minute. (3) During the&#xD;
      infusion, physicians should monitor adverse reactions such as headache, dizziness, flushing&#xD;
      or sweating. If any occur, the infusion speed must be reduced. If the patients remain&#xD;
      uncomfortable, nimodipine should be withdrawn. (4) Liver and kidney function should be&#xD;
      monitored throughout nimodipine administration.&#xD;
&#xD;
      Although nimodipine is relatively safe, there is still a risk of some adverse effects, such&#xD;
      as cardiovascular system reactions (blood pressure decreases, bradycardia, angina, and&#xD;
      atrioventricular block), headache, dizziness, edema, and liver and kidney dysfunction. It is&#xD;
      necessary to determine the optimal therapeutic time window and dose of nimodipine in&#xD;
      multi-center, large-scale clinical trials.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 2014</start_date>
  <completion_date type="Actual">September 2015</completion_date>
  <primary_completion_date type="Actual">September 2015</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Neurological deficits</measure>
    <time_frame>up to 90 days</time_frame>
    <description>Neurological deficits after stroke will be assessed using the National Institute of Health Stroke Scale scores</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">72</enrollment>
  <condition>Cerebral Infarction</condition>
  <arm_group>
    <arm_group_label>Saline + citicoline</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The control group will receive physiological saline + citicoline 2.0 g, once a day, via intravenous drip, for 10 consecutive days. Patients will receive additional drugs to treat dehydration, prevent infection and upper gastrointestinal bleeding, and maintain water and electrolyte balance. Patients with complications will receive symptomatic treatment.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Nimodipine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The treatment group will receive 10 mg of nimodipine in 500 ml of physiological saline via intravenous drip, at a rate of 1-2 drops per minute initially, increasing gradually until systolic pressure decreases by 10 mmHg. Maximum drip speed is 10 drops/minute, administered once a day for 7 consecutive days. The nimodipine must be kept in the dark. Blood pressure and heart rate will be monitored throughout the administration period.&#xD;
Patients in control group will receive additional drugs to treat dehydration, prevent infection and upper gastrointestinal bleeding, and maintain water and electrolyte balance. Patients with complications will receive symptomatic treatment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nimodipine</intervention_name>
    <description>Jiangsu Jichuan Pharmaceutical Co., Ltd., Jiangsu Province, China</description>
    <arm_group_label>Nimodipine</arm_group_label>
    <other_name>The treatment group</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Saline + citicoline</intervention_name>
    <description>physiological saline + citicoline 2.0 g, once a day, via intravenous drip, for 10 consecutive days.</description>
    <arm_group_label>Saline + citicoline</arm_group_label>
    <other_name>The control group</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  First onset at age ≤ 80 years, no other severe medical complications;&#xD;
&#xD;
          -  Clear consciousness or mild disturbance of consciousness; paralysis of upper and lower&#xD;
             extremities on one side with grade 0-3 muscle strength in paralyzed limbs;&#xD;
&#xD;
          -  CT reveals early massive cerebral infarction (without cerebral hemorrhage or old&#xD;
             infarction);&#xD;
&#xD;
          -  Blood pressure within, or higher than, the normal range.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Clinical manifestations are noticeably improved before treatment;&#xD;
&#xD;
          -  Disorders of consciousness, manifesting as severe lethargy or coma;&#xD;
&#xD;
          -  Mild neurological deficits, such as pure sensory disturbances, ataxia, dysarthria, and&#xD;
             hemiparesis;&#xD;
&#xD;
          -  Severe hypotension (systolic pressure &lt; 90 mmHg, diastolic pressure &lt; 60 mmHg);&#xD;
&#xD;
          -  Heart rate &lt; 60 BPM; sinus bradycardia;&#xD;
&#xD;
          -  Severe heart, brain or kidney dysfunction, or malignant tumor.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Runhui Li, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Central hospital affiliated to shenyang medical college</affiliation>
  </overall_official>
  <removed_countries>
    <country>China</country>
  </removed_countries>
  <verification_date>April 2018</verification_date>
  <study_first_submitted>September 22, 2014</study_first_submitted>
  <study_first_submitted_qc>September 23, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2014</study_first_posted>
  <last_update_submitted>April 28, 2018</last_update_submitted>
  <last_update_submitted_qc>April 28, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">May 1, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Fengtian Hospital</investigator_affiliation>
    <investigator_full_name>Runhui Li</investigator_full_name>
    <investigator_title>Director</investigator_title>
  </responsible_party>
  <keyword>nimodipine</keyword>
  <keyword>acute massive cerebral infarction</keyword>
  <keyword>Cerebral Infarction</keyword>
  <keyword>optimal therapeutic time window</keyword>
  <keyword>optimal dose</keyword>
  <keyword>multi-center</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cerebral Infarction</mesh_term>
    <mesh_term>Infarction</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nimodipine</mesh_term>
    <mesh_term>Cytidine Diphosphate Choline</mesh_term>
  </intervention_browse>
  <!-- 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/NCT02248233
org study id: FengtianH-RHL-001
nct id: NCT02248233
lead sponsor: 
has dmc: No
Massive cerebral infarction is an ischemic stroke caused by complete blockage of the internal
      carotid artery, middle cerebral artery, or their cortical branches. The widespread
      infarction, pathological severity and high fatality rate associated with massive cerebral
      infarction pose a major threat to affected patients. However, there is a lack of unified
      diagnostic criteria. Many researchers use Adams' classification, in which massive cerebral
      infarction is diagnosed when the following criteria are met: infarct size > 13 cm2; a major
      brain-feeding artery is involved; the focal site affects more than two cerebral lobes;
      infarct diameter line ≥ 3 cm in internal capsule of striatum.

      Prolonged cerebral ischemia/reperfusion can induce complex secondary changes in brain tissue,
      so the use of neuroprotective agents is very important. Remarkable progress has been made
      over the last decade in understanding the protective effect of calcium antagonists against
      cerebral ischemia. In particular, the liposoluble dihydropyridine Ca2+ antagonist nimodipine
      selectively acts on cerebral vessels and neurons and can protect ischemic brain tissue,
      providing a new way of treating ischemic cerebrovascular disease.

      Preclinical and clinical tests have shown that nimodipine has a protective effect on ischemic
      brain tissue, and indicate that patients should take the drug as soon as possible. However,
      there are no reports of double-blind, randomized, controlled clinical trials addressing the
      administration of nimodipine via intravenous drip within the time window for successful
      treatment of acute massive cerebral infarction.
In the clinic, physicians are reluctant to use thrombolysis, Defibrase and anticoagulation
      therapy because of the severity of symptoms, poor prognosis, risk of hemorrhage and high
      fatality rate that occur with acute massive cerebral infarction. Nimodipine, as a selective
      Ca2+ antagonist, is highly liposoluble, effectively crosses the blood-brain barrier,
      selectively acts on intracranial blood vessels, and is an accepted neuroprotective agent that
      can be applied in the clinic. The aim of the present study is to perform a double-blind,
      randomized and controlled trial of the clinical efficacy and safety of nimodipine
      administered as an intravenous drip in the early stages of acute massive cerebral infarction.

      Patients will receive nimodipine within 3 days of infarction onset. We will closely monitor
      the following: (1) Blood pressure and heart rate of the patient before treatment, since
      nimodipine is contraindicated in patients with hypotension and low heart rate. Where blood
      pressure is ≥ 100/80 mmHg and heart rate ≥ 60 BPM, nimodipine will be administered. (2) Speed
      of infusion. This should not be too fast; we suggest 1-2 drops per minute initially,
      increasing gradually until the drop in systolic pressure exceeds 10 mmHg. The average drip
      speed should be 6-8 drops/minute, and the fastest drip speed 10 drops/minute. (3) During the
      infusion, physicians should monitor adverse reactions such as headache, dizziness, flushing
      or sweating. If any occur, the infusion speed must be reduced. If the patients remain
      uncomfortable, nimodipine should be withdrawn. (4) Liver and kidney function should be
      monitored throughout nimodipine administration.

      Although nimodipine is relatively safe, there is still a risk of some adverse effects, such
      as cardiovascular system reactions (blood pressure decreases, bradycardia, angina, and
      atrioventricular block), headache, dizziness, edema, and liver and kidney dysfunction. It is
      necessary to determine the optimal therapeutic time window and dose of nimodipine in
      multi-center, large-scale clinical trials.
allocation: Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Neurological deficits
time frame: up to 90 days
description: Neurological deficits after stroke will be assessed using the National Institute of Health Stroke Scale scores
arm group label: Saline + citicoline
arm group type: Experimental
description: The control group will receive physiological saline + citicoline 2.0 g, once a day, via intravenous drip, for 10 consecutive days. Patients will receive additional drugs to treat dehydration, prevent infection and upper gastrointestinal bleeding, and maintain water and electrolyte balance. Patients with complications will receive symptomatic treatment.
arm group label: Nimodipine
arm group type: Experimental
description: The treatment group will receive 10 mg of nimodipine in 500 ml of physiological saline via intravenous drip, at a rate of 1-2 drops per minute initially, increasing gradually until systolic pressure decreases by 10 mmHg. Maximum drip speed is 10 drops/minute, administered once a day for 7 consecutive days. The nimodipine must be kept in the dark. Blood pressure and heart rate will be monitored throughout the administration period.
Patients in control group will receive additional drugs to treat dehydration, prevent infection and upper gastrointestinal bleeding, and maintain water and electrolyte balance. Patients with complications will receive symptomatic treatment.
intervention type: Drug
intervention name: Nimodipine
description: Jiangsu Jichuan Pharmaceutical Co., Ltd., Jiangsu Province, China
arm group label: Nimodipine
other name: The treatment group
intervention type: Drug
intervention name: Saline + citicoline
description: physiological saline + citicoline 2.0 g, once a day, via intravenous drip, for 10 consecutive days.
arm group label: Saline + citicoline
other name: The control group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Runhui Li, M.D.
role: Principal Investigator
affiliation: Central hospital affiliated to shenyang medical college
country: China
responsible party type: Principal Investigator
investigator affiliation: Fengtian Hospital
investigator full name: Runhui Li
investigator title: Director
mesh term: Cerebral Infarction
mesh term: Infarction
mesh term: Nimodipine
mesh term: Cytidine Diphosphate Choline