Nimodipine for Treating Acute Massive Cerebral Infarction

Sponsor

Fengtian Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT02248233

Collaborator

(none)

Enrollment

Arms

Actual Duration (Months)

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Cerebral Infarction	Drug: Nimodipine Drug: Saline + citicoline	Phase 4

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

72 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Nimodipine for Treating Acute Massive Cerebral Infarction: a Randomized, Double-blind, Controlled Clinical Study

Actual Study Start Date :

Oct 1, 2014

Actual Primary Completion Date :

Sep 1, 2015

Actual Study Completion Date :

Sep 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Saline + citicoline 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.	Drug: Saline + citicoline physiological saline + citicoline 2.0 g, once a day, via intravenous drip, for 10 consecutive days. Other Names: The control group
Experimental: Nimodipine 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.	Drug: Nimodipine Jiangsu Jichuan Pharmaceutical Co., Ltd., Jiangsu Province, China Other Names: The treatment group

Arm

Intervention/Treatment

Experimental: Saline + citicoline

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.

Drug: Saline + citicoline

physiological saline + citicoline 2.0 g, once a day, via intravenous drip, for 10 consecutive days.

Other Names:

The control group

Experimental: Nimodipine

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.

Drug: Nimodipine

Jiangsu Jichuan Pharmaceutical Co., Ltd., Jiangsu Province, China

Other Names:

The treatment group

Outcome Measures

Primary Outcome Measures

Neurological deficits [up to 90 days]
Neurological deficits after stroke will be assessed using the National Institute of Health Stroke Scale scores

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

First onset at age ≤ 80 years, no other severe medical complications;
Clear consciousness or mild disturbance of consciousness; paralysis of upper and lower extremities on one side with grade 0-3 muscle strength in paralyzed limbs;
CT reveals early massive cerebral infarction (without cerebral hemorrhage or old infarction);
Blood pressure within, or higher than, the normal range.

Exclusion Criteria:

Clinical manifestations are noticeably improved before treatment;
Disorders of consciousness, manifesting as severe lethargy or coma;
Mild neurological deficits, such as pure sensory disturbances, ataxia, dysarthria, and hemiparesis;
Severe hypotension (systolic pressure < 90 mmHg, diastolic pressure < 60 mmHg);
Heart rate < 60 BPM; sinus bradycardia;
Severe heart, brain or kidney dysfunction, or malignant tumor.