Vitamin K1 in the Treatment of Spontaneous Intracerebral Hemorrhage

Multicenter Randomized Controlled Trial of Vitamin K1 in the Treatment of Spontaneous Intracerebral Hemorrhage

In order to determine the effectiveness and safety of early vitamin K1 use in reducing the risk of bleeding and improving prognosis in patients with spontaneous intracerebral hemorrhage. Patients with spontaneous intracerebral hemorrhage (excluding rupture of aneurysm and vascular malformation) will be randomly divided into experimental group and control group. All the patients in the two groups were treated according to the guideline of spontaneous intracerebral hemorrhage. Patients in the experimental group was treated with intravenous injection of vitamin K1 20mg once a day for 2 days after admission, and the patients in control group was treated with normal saline as a control. The hematoma volume, coagulation function, platelet levels and GCS scales of the two groups will be recorded in 0d, 1d, 3d, 7d post bleeding stroke, furthermore, length of ICU stay and total hospitalization, incidence of complications during hospitalization are to be recorded. During the follow-up, mRS score will be recorded at 1m and 6m post bleeding stroke.

Study Overview

• Status: Unknown
• Conditions: Intracerebral Haemorrhage in Cerebellum
• Intervention / Treatment: Drug: Vitamin K 1; Drug: normal saline

Detailed Description

Spontaneous intracerebral hemorrhage is a common disease in the department of neurosurgery, which often leads to long-term coma and severe neurological dysfunction. The amount of cerebral hemorrhage is directly related to the prognosis of the patients, and a small number of patients still suffer from the adverse consequences of delayed bleeding after active treatment. Vitamin K1 is a necessary ingredient in the liver to produce clotting factors II, VII, IX, and X, and vitamin K1 supplementation increases clotting function. On the contrary, vitamin K1 increases the risk of thrombosis. In this study, patients with spontaneous intracerebral hemorrhage (excluding rupture of aneurysm and vascular malformation) will be randomly divided into experimental group and control group. All the patients in the two groups were treated according to the guideline of spontaneous intracerebral hemorrhage. Patients in the experimental group was treated with intravenous injection of vitamin K1 20mg once a day for 2 days after admission, and the patients in control group was treated with normal saline as a control. The hematoma volume, coagulation function, platelet levels and GCS scales of the two groups will be recorded in 0d, 1d, 3d, 7d post bleeding stroke, furthermore, length of ICU stay and total hospitalization, incidence of complications during hospitalization are to be recorded. During the follow-up, mRS score will be recorded at 1m and 6m post bleeding stroke. Finally, the effectiveness and safety of early vitamin K1 use in reducing the risk of bleeding and improving prognosis in patients with spontaneous intracerebral hemorrhage will be analyzed.

• Study Type: Interventional
• Enrollment (Anticipated): 400
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Shenzhen, Guangdong, China, 518000
      • Shenzhen Second People's Hospital
    • Shenzhen, Guangdong, China, 518035
      • The fifth people's hospital of Longgang District, Shenzhen
    • Shenzhen, Guangdong, China, 518102
      • Baoan District central hospital of Shenzhen
    • Shenzhen, Guangdong, China, 518104
      • Shajing hospital of Baoan District ,Shenzhen
    • Shenzhen, Guangdong, China, 518116
      • The second People's hospital of Longgang District, Shenzhen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Spontaneous intracerebral hemorrhage (Non - aneurysmal or arteriovenous malformations which confirmed by cerebral arterial CT enhancement or DSA);
• Age 18-65 years, male or non-pregnant female;
• GCS score at admission (4 to12);
• during the hospitalization, no urokinase and other hemostatic drugs were used except for etamsylate and vitamin K1;
• informed consent signed by the patient's family

Exclusion Criteria:

• irregular lobulated hematoma (volume of hematoma can not be calculated accurately), such as intraventricular hemorrhage;
• severe liver disease or impaired liver function;
• pregnant or lactating women;
• history of using anticoagulation or antiplatelet aggregation drug (including Cilostazol, aspirin, dipyridamole, heparin, low molecular weight heparin, hirudin, dabigatran, and warfarin);
• non-accepted informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: research group; normal saline 100ml+ vitamin K1 20mg ivgtt qd day0 and day1。	Drug: Vitamin K 1; Research group use Vitamin K1
Placebo Comparator: placebo group; normal saline100ml + normal saline 2 ml ivgtt qd day0 and day1	Drug: normal saline; Placebo group use normal saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The volume of cerebral hemorrhage	The volume of cerebral hemorrhage at certain time post onset（ml）	Day0
The volume of cerebral hemorrhage	The volume of cerebral hemorrhage at certain time post onset（ml）	Day3
The volume of cerebral hemorrhage	The volume of cerebral hemorrhage at certain time post onset（ml）	Day7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Activated Partial Thromboplastin Time（s）at certain time post onset	Activated Partial Thromboplastin Time（s）	Day0
The Activated Partial Thromboplastin Time（s）at certain time post onset	Activated Partial Thromboplastin Time（s）	Day3
The Activated Partial Thromboplastin Time（s）at certain time post onset	Activated Partial Thromboplastin Time（s）	Day7
The condition of Platelet level at certain time post onset	The condition of Platelet level at certain time post onset（10^9/L）	Day0
The condition of Platelet level at certain time post onset	The condition of Platelet level at certain time post onset（10^9/L）	Day3
The condition of Platelet level at certain time post onset	The condition of Platelet level at certain time post onset（10^9/L）	Day7
The condition of GCS scale post(3-15) at certain time post onset	The condition of GCS scale post(3-15) at certain time post onset	Day0
The condition of GCS scale post(3-15) at certain time post onset	The condition of GCS scale post(3-15) at certain time post onset	Day3
The condition of GCS scale post(3-15) at certain time post onset	The condition of GCS scale post(3-15) at certain time post onset	Day7
The prothrombin time(s) at certain time post onset	prothrombin time(s)	Day0
The prothrombin time(s) at certain time post onset	prothrombin time(s)	Day3
The prothrombin time(s) at certain time post onset	prothrombin time(s)	Day7
The Fibrinogen (g/L)at certain time post onset	Fibrinogen (g/L)	Day0
The Fibrinogen (g/L)at certain time post onset	Fibrinogen (g/L)	Day3
The Fibrinogen (g/L)at certain time post onset	Fibrinogen (g/L)	Day7
The Thrombin Time(s) at certain time post onset	Thrombin Time(s)	Day0
The Thrombin Time(s) at certain time post onset	Thrombin Time(s)	Day3
The Thrombin Time(s) at certain time post onset	Thrombin Time(s)	Day7

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
length of stay in ICU	length of stay in ICU	about two weeks
Total hospital stay	Total hospital stay	about one month
Complications1	neurologic complications	6 month post onset
The Modified Rankin Scale (mRS)	The scale runs from 0-6, running from perfect health without symptoms to death.0 - No symptoms.1 - No significant disability. Able to carry out all usual activities, despite some symptoms.2 - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities. 3 - Moderate disability. Requires some help, but able to walk unassisted. 4 - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted. 5 - Severe disability. Requires constant nursing care and attention, bedridden, incontinent. 6 - Dead.	month 1 post onset
The Modified Rankin Scale (mRS)	The scale runs from 0-6, running from perfect health without symptoms to death.0 - No symptoms.1 - No significant disability. Able to carry out all usual activities, despite some symptoms.2 - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities. 3 - Moderate disability. Requires some help, but able to walk unassisted. 4 - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted. 5 - Severe disability. Requires constant nursing care and attention, bedridden, incontinent. 6 - Dead.	month 6 post onset
Complications2	infection complications	6 month post onset
Complications3	complications of coagulation	6 month post onset

Collaborators and Investigators

• Sponsor: HUANG XIANJIAN

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2017
• Primary Completion (Anticipated): October 31, 2018
• Study Completion (Anticipated): July 1, 2019

Study Registration Dates

• First Submitted: October 29, 2017
• First Submitted That Met QC Criteria: December 31, 2017
• First Posted (Actual): January 3, 2018

Study Record Updates

• Last Update Posted (Actual): January 4, 2018
• Last Update Submitted That Met QC Criteria: January 3, 2018
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: outcome; effectiveness; vitamin K1; spontaneous intracerebral hemorrhage
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Intracranial Hemorrhages; Hemorrhage; Cerebral Hemorrhage; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Micronutrients; Vitamins; Antifibrinolytic Agents; Hemostatics; Coagulants; Vitamin K; Vitamin K 1
• Other Study ID Numbers: HUANGXIANJIAN20170608

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No