Nimodipine for Treating Acute Massive Cerebral Infarction
Condition: Cerebral Infarction
MeSH terms: Cerebral Infarction; Infarction
Study type: Interventional
Phase: Phase 4

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Nimodipine; Saline + citicoline
Intervention type(s): Drug; Drug
Intervention description(s): Jiangsu Jichuan Pharmaceutical Co., Ltd., Jiangsu Province, China; physiological saline + citicoline 2.0 g, once a day, via intravenous drip, for 10 consecutive days.
Other intervention name(s): The treatment group; The control group
Intervention MeSH terms: Nimodipine; Cytidine Diphosphate Choline
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: nimodipine; acute massive cerebral infarction; Cerebral Infarction; optimal therapeutic time window; optimal dose; multi-center