Back to resultsA Phase 4 Clinical Study to Investigate the Efficacy and Safety of Naloxone HCI IV in Patients With Stroke
Primary Purpose
Stroke, Acute
Status
Completed
Phase
Phase 4
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Naloxone hydrochloride 5.0mg/5ml
Sodium Chloride 45mg/5ml
Sponsored by
About this trial
This is an interventional treatment trial for Stroke, Acute focused on measuring cerebral infarction or cerebral hemmorrhage
Eligibility Criteria
Inclusion Criteria:
- Subjects who are males or females aged ≥19 years
- Patients with a stroke who can administer drugs for clinical trials within 48 hours from stroke onset
- Patients with a NIHSS score of 5-20 or GCS score of 8-13 at screening assessment (In the case of cerebral infarction, the NIHSS is evaluated, and cerebral hemorrhage, the GCS is evaluated.)
- Patients with a mRS(Modified Rankin Score) > 2 after stroke and immediately before randomization.
- Patients who or whose representative voluntarily agrees to this study and has given a written informed consent.
Exclusion Criteria:
- Subjects with medical history of hypersensitivity reaction to investigational product or ingredients.
- Patients with non-narcotic central nerve inhibitors such as barbital drugs or respiratory depression caused by pathological causes.
- Patients who have not passed the wash-out time after administration of opioid analgesics.
- Subjects with Renal dysfunction whose creatine level is more than twice the normal upper limit in screening tests
- Subjects with Liver dysfunction whose AST/ALT level is more than three times the normal upper limit in screening tests.
- Subjects with Systolic blood pressure less than 90 mmHg or more than 220 mmHg during screening.
- Patients with a mRS > 2 before stroke onset.
- Patients with a history of epilepsy.
- Patients with myocardial infarction within 1 month.
- Pregnant or lactating women
- Patients who have passed more than 48 hours since the onset of symptoms.
- Subjects who received other therapeutic investigational product within the last 30 days.
- Patients who transient ischemic attack.
- Patients whose life expectancy is less than 3 months due to comorbidities other than stroke
- Thrombolysis (including non-drug treatments such as thrombolytic drugs and mechanical procedures used in thrombolysis) or extraventricular drainage (surgical treatment) has been performed or is scheduled to be performed.
- Thrombolytic agent used in thrombolysis[ex. Streptokinase, Alteplase, Anistreplase, Urokinase, Reteplase, Tenecteplase, Tissue-plasminogen activator (t-PA), Single-chain urokinase-type plasminogen activator (Scu-PA), Lanoteplase, Monteplase, Plasminogen activator inhibitors (PAI)]
- Surgical treatment [ex. mechanical thrombectomy, external ventricular drainage (EVD), extralesional drainage (ELD), decompression], Subarachnoid hemorrhage (SH), Trauma patients [ex. SH coiling, traumatic intracranial hemorrhage (ICH)], Among patients with infarction, patients who need or are scheduled to perform Depressive craniomy.
- Any condition that, in the opinion of the investigator, would inappropriate to participate in the clinical trial
Sites / Locations
- Inha University Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Naloxone hydrochloride 5.0mg/5ml
Placebo
Arm Description
Naloxone hydrochloride 60mg (However, the dose may be appropriately increased or decreased according to the judgement of the investigator)
Placebo 60ml (However, the dose may be appropriately increased or decreased according to the judgement of the investigator)
Outcomes
Primary Outcome Measures
Percentage of subjects who have the modified Rankin Scale (mRS) score of 2 or less on Day 90
Modified Rankin Scale is an index that evaluates the patient's global functional outcome according to the independence of daily life and the degree of need for help from others. It is evaluated in seven stages (0 to 6 points), from asymptomatic to death. The higher score means a worse outcome, and 3 to 6 points are considered to be poor functional outcome.
Secondary Outcome Measures
The change from baseline in Modified Rankin Score (mRS) up to Day 90
Modified Rankin Scale is an index that evaluates the patient's global functional outcome according to the independence of daily life and the degree of need for help from others. It is evaluated in seven stages (0 to 6 points), from asymptomatic to death. The higher score means a worse outcome, and 3 to 6 points are considered to be poor functional outcome.
The change from baseline in Modified Barthel Index (mBI) up to Day 90.
The change from baseline in EuroQol five dimensions questionnaire(EQ-5D) up to Day 90
The change from baseline in Korean Mini-Mental State Examination(KMMSE) up to Day 90
The change from baseline in Global Deterioration Scale (GDS) up to Day 90
The GDS is a staging scale indicating deterioration in dementia, The scale details clinical descriptions of seven major distinguishable stages, ranging from normal cognition to severe dementia.
Stages 1 - 3 are the pre dementia stages. Stages 4 -7 reflect the stages of dementia. People beginning with stage 5 are no longer survive without assistance.
The change from baseline in National institutes of health stroke scale(NIHSS) up to Day 90
It will be evaluated in patients with cerebral infarction.
The NIHSS is a tool used by healthcare providers to objectively quantify the impairment caused by a stroke.
The NIHSS is composed of 11 items, each of which scores a specific ability between a 0 and 4.
For each item, a score of 0 typically indicates normal function in that specific ability, while a higher score is indicative of some level of impairment.
The individual scores from each item are summed in order to calculate a patient's total NIHSS score.
The maximum possible score is 42, with the minimum score being a 0.
The change from baseline in Glasgow Coma Scale(GCS) up to Day 90
It will be evaluated in patients with cerebral hemorrhage. The Glasgow Coma Scale (GCS) is used to objectively describe the extent of impaired consciousness in all types of acute medical and trauma patients.
The Glasgow Coma Scale divides into three parameters: best eye response (E), best verbal response (V) and best motor response (M). The levels of response in the components of the Glasgow Coma Scale are 'scored' from 1, for no response, up to normal values of 4 (Eye-opening response) 5 ( Verbal response) and 6 (Motor response) The total Coma Score thus has values between three and 15, three being the worst and 15 being the highest.
The odds ratio of the factors which contribute to a mRS score to be less than or equal to 2 on Day 90
The factors, such as sex, age, disease subtype and severity, investigational product compliance, which might impact the mRS score to be less than or equal to 2 will be analyzed.
Full Information
NCT ID
NCT05301712
First Posted
March 11, 2022
Last Updated
August 11, 2023
Sponsor
Samjin Pharmaceutical Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT05301712
Brief Title
A Phase 4 Clinical Study to Investigate the Efficacy and Safety of Naloxone HCI IV in Patients With Stroke
Official Title
A Placebo Controlled, Double-blind, Randomized, Multicenter Study to Evaluate the Efficacy and Safety of Naloxone HCl IV in Patients With Stroke
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
August 7, 2018 (Actual)
Primary Completion Date
October 25, 2022 (Actual)
Study Completion Date
July 10, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Samjin Pharmaceutical Co., Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This clinical trial was planned for the purpose to re-evaluate the safety and efficacy of naloxone hydrochloride in ischemic cerebral nerve disorders caused by stroke and cerebral hemorrhage.
Eligible subjects will be randomized to the naloxone hydrochloride group or placebo group at 1:1 ratio.
Also, factors, such as disease subtype and severity, which might impact the efficacy endpoints will be used to stratify.
- Stratification factor: cerebral infarction (NIHSS 5-15 points or 16-20 points) or cerebral hemorrhage
Administration of investigational product should be started within 48 hours from the onset of symptoms.
Subject receive the investigational product 7 consecutive times (for 7 days) in a single dose of intravenous infusion for 24 hours.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stroke, Acute
Keywords
cerebral infarction or cerebral hemmorrhage
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
This clinical trial was planned for the purpose of re-evaluating ischemic cerebral nerve disorders caused by stroke and cerebral hemorrhage the efficacy and effects of naloxone hydrochloride.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
446 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Naloxone hydrochloride 5.0mg/5ml
Arm Type
Experimental
Arm Description
Naloxone hydrochloride 60mg (However, the dose may be appropriately increased or decreased according to the judgement of the investigator)
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo 60ml (However, the dose may be appropriately increased or decreased according to the judgement of the investigator)
Intervention Type
Drug
Intervention Name(s)
Naloxone hydrochloride 5.0mg/5ml
Other Intervention Name(s)
Noloxone hydrochloride 5mg
Intervention Description
Initial dose: 4mg, Intravenous injection
Continuous dose: 8mg(mixed with 1000ml of 5% Dextrose water or saline solution) per day, Intravenous infusion for 7days
Total dose: 4mg+8mg/day*7=60mg
Intervention Type
Drug
Intervention Name(s)
Sodium Chloride 45mg/5ml
Other Intervention Name(s)
Placebo
Intervention Description
Initial dose: 4ml, Intravenous injection
Continuous dose: 8ml (mixed with 1000ml of 5% Dextrose water or saline solution) per day, Intravenous infusion for 7days
Total dose: 4ml+8ml/day*7=60ml
Primary Outcome Measure Information:
Title
Percentage of subjects who have the modified Rankin Scale (mRS) score of 2 or less on Day 90
Description
Modified Rankin Scale is an index that evaluates the patient's global functional outcome according to the independence of daily life and the degree of need for help from others. It is evaluated in seven stages (0 to 6 points), from asymptomatic to death. The higher score means a worse outcome, and 3 to 6 points are considered to be poor functional outcome.
Time Frame
Day 90
Secondary Outcome Measure Information:
Title
The change from baseline in Modified Rankin Score (mRS) up to Day 90
Description
Modified Rankin Scale is an index that evaluates the patient's global functional outcome according to the independence of daily life and the degree of need for help from others. It is evaluated in seven stages (0 to 6 points), from asymptomatic to death. The higher score means a worse outcome, and 3 to 6 points are considered to be poor functional outcome.
Time Frame
Baseline, Day 3, Day 7, Day 14(or discharge), Day 30 and Day 90
Title
The change from baseline in Modified Barthel Index (mBI) up to Day 90.
Time Frame
Baseline, Day 3, Day 7, Day 14(or discharge), Day 30 and Day 90
Title
The change from baseline in EuroQol five dimensions questionnaire(EQ-5D) up to Day 90
Time Frame
Baseline, Day 3, Day 7, Day 14(or discharge), Day 30 and Day 90
Title
The change from baseline in Korean Mini-Mental State Examination(KMMSE) up to Day 90
Time Frame
Baseline, Day 3, Day 7, Day 14(or discharge), Day 30 and Day 90
Title
The change from baseline in Global Deterioration Scale (GDS) up to Day 90
Description
The GDS is a staging scale indicating deterioration in dementia, The scale details clinical descriptions of seven major distinguishable stages, ranging from normal cognition to severe dementia.
Stages 1 - 3 are the pre dementia stages. Stages 4 -7 reflect the stages of dementia. People beginning with stage 5 are no longer survive without assistance.
Time Frame
Baseline, Day 3, Day 7, Day 14(or discharge), Day 30 and Day 90
Title
The change from baseline in National institutes of health stroke scale(NIHSS) up to Day 90
Description
It will be evaluated in patients with cerebral infarction.
The NIHSS is a tool used by healthcare providers to objectively quantify the impairment caused by a stroke.
The NIHSS is composed of 11 items, each of which scores a specific ability between a 0 and 4.
For each item, a score of 0 typically indicates normal function in that specific ability, while a higher score is indicative of some level of impairment.
The individual scores from each item are summed in order to calculate a patient's total NIHSS score.
The maximum possible score is 42, with the minimum score being a 0.
Time Frame
Baseline, Day 3, Day 7, Day 14(or discharge), Day 30 and Day 90
Title
The change from baseline in Glasgow Coma Scale(GCS) up to Day 90
Description
It will be evaluated in patients with cerebral hemorrhage. The Glasgow Coma Scale (GCS) is used to objectively describe the extent of impaired consciousness in all types of acute medical and trauma patients.
The Glasgow Coma Scale divides into three parameters: best eye response (E), best verbal response (V) and best motor response (M). The levels of response in the components of the Glasgow Coma Scale are 'scored' from 1, for no response, up to normal values of 4 (Eye-opening response) 5 ( Verbal response) and 6 (Motor response) The total Coma Score thus has values between three and 15, three being the worst and 15 being the highest.
Time Frame
Baseline, Day 3, Day 7, Day 14(or discharge), Day 30 and Day 90
Title
The odds ratio of the factors which contribute to a mRS score to be less than or equal to 2 on Day 90
Description
The factors, such as sex, age, disease subtype and severity, investigational product compliance, which might impact the mRS score to be less than or equal to 2 will be analyzed.
Time Frame
Day 90
10. Eligibility
Sex
All
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subjects who are males or females aged ≥19 years
Patients with a stroke who can administer drugs for clinical trials within 48 hours from stroke onset
Patients with a NIHSS score of 5-20 or GCS score of 8-13 at screening assessment (In the case of cerebral infarction, the NIHSS is evaluated, and cerebral hemorrhage, the GCS is evaluated.)
Patients with a mRS(Modified Rankin Score) > 2 after stroke and immediately before randomization.
Patients who or whose representative voluntarily agrees to this study and has given a written informed consent.
Exclusion Criteria:
Subjects with medical history of hypersensitivity reaction to investigational product or ingredients.
Patients with non-narcotic central nerve inhibitors such as barbital drugs or respiratory depression caused by pathological causes.
Patients who have not passed the wash-out time after administration of opioid analgesics.
Subjects with Renal dysfunction whose creatine level is more than twice the normal upper limit in screening tests
Subjects with Liver dysfunction whose AST/ALT level is more than three times the normal upper limit in screening tests.
Subjects with Systolic blood pressure less than 90 mmHg or more than 220 mmHg during screening.
Patients with a mRS > 2 before stroke onset.
Patients with a history of epilepsy.
Patients with myocardial infarction within 1 month.
Pregnant or lactating women
Patients who have passed more than 48 hours since the onset of symptoms.
Subjects who received other therapeutic investigational product within the last 30 days.
Patients who transient ischemic attack.
Patients whose life expectancy is less than 3 months due to comorbidities other than stroke
Thrombolysis (including non-drug treatments such as thrombolytic drugs and mechanical procedures used in thrombolysis) or extraventricular drainage (surgical treatment) has been performed or is scheduled to be performed.
Thrombolytic agent used in thrombolysis[ex. Streptokinase, Alteplase, Anistreplase, Urokinase, Reteplase, Tenecteplase, Tissue-plasminogen activator (t-PA), Single-chain urokinase-type plasminogen activator (Scu-PA), Lanoteplase, Monteplase, Plasminogen activator inhibitors (PAI)]
Surgical treatment [ex. mechanical thrombectomy, external ventricular drainage (EVD), extralesional drainage (ELD), decompression], Subarachnoid hemorrhage (SH), Trauma patients [ex. SH coiling, traumatic intracranial hemorrhage (ICH)], Among patients with infarction, patients who need or are scheduled to perform Depressive craniomy.
Any condition that, in the opinion of the investigator, would inappropriate to participate in the clinical trial
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dong Keun Hyun, M.D.,Ph.D
Organizational Affiliation
Inha University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Inha University Hospital
City
Incheon
Country
Korea, Republic of
12. IPD Sharing Statement
Learn more about this trial
A Phase 4 Clinical Study to Investigate the Efficacy and Safety of Naloxone HCI IV in Patients With Stroke
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