Management of Cerebral Vascular Spasm in Posttraumatic Subarachnoid Hemorrhage Using Combination Therapy

Sponsor

Zagazig University (Other)

Overall Status

Completed

CT.gov ID

NCT05131867

Collaborator

(none)

Enrollment

Locations

Arms

5.9

Actual Duration (Months)

Patients Per Site

2.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To evaluate the efficacy and safety of oral Nimodipine and IV milrinone combination therapy for management of cerebral spasm after aneurysmal subarachnoid hemorrhage.

Condition or Disease	Intervention/Treatment	Phase
Oral Nimodipine Milrinone Vascular Spasm After Traumatic Subarachnoidhaemorrhage	Drug: nimodipine Drug: Oral Nimodipine and milrinone	Phase 2

Detailed Description

after being informed about the study and potential risks. All patients giving written consent will be randomized by double-blind manner into 2groups each one containing 15 patients.

Group 1(n =15 ):the patients will receive nimodipine (60 mg/4 hours) orally or via nasogastric tube In group 2(n =15 ): the patients will receive Oral Nimodipine (60 mg/4) will be given orally or in the gastric tube also from the first day of admission, then after the diagnosis of vasospasm is confirmed, start milrinone.

Study Design

Study Type:

Interventional

Actual Enrollment :

30 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Masking Description:

double

Primary Purpose:

Treatment

Official Title:

Management of Cerebral Vascular Spasm in Posttraumatic Subarachnoid Hemorrhage Using Combination Therapy of Oral Nimodipine and Intravenous Milrinone: Randomized Clinical Trial

Actual Study Start Date :

Nov 24, 2021

Actual Primary Completion Date :

May 23, 2022

Actual Study Completion Date :

May 24, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: triple H group The patients will receive nimodipine (60 mg/4 hours) orally or via nasogastric tube from the first day of admission, then after the diagnosis of vasospasm is confirmed, Triple H therapy (hypertension, hypervolemia and hemodilution) will be started. norepnnephrine (0.01-0.2ug/kg/min) to mentain main arterial blood pressure >100mmhg and hypervolemia to maintain the CVP around 12---14 mmHg and hemodilution to maintain the haematocrit between 30% and 33%.	Drug: nimodipine (60 mg/4 hours) orally or via nasogastric tube
Active Comparator: Milrinone group The patients will receive oral Nimodipine (60 mg/4) will be given orally or in the gastric tube also from the first day of admission, then after the diagnosis of vasospasm is confirmed, start milrinone bolus of 0.1-0.2 mg/kg followed by 0.75mcg/k/min, if no response after 30min increase the infusion to 1-25mcg/kg/min with maintaining CVP 5:8. Norepinephrine (0.01-0.2ug/kg/min) is used only to restore the mean arterial pressure (MAP) to its previous values If there was no recurrence of symptoms after 72 h, we decreased the milrinone infusion by 0.25 mcg/kg/min every 24 or 48 h until discontinuation. If there are any recurrent of symptoms of vasospasm, the patients are placed back on the dose they were previously receiving. If required, another Milrinone bolus is administered if the patient's deficits do not revert12.	Drug: Oral Nimodipine and milrinone Oral Nimodipine then after the diagnosis of vasospasm is confirmed, start milrinone bolus

Arm

Intervention/Treatment

Active Comparator: triple H group

The patients will receive nimodipine (60 mg/4 hours) orally or via nasogastric tube from the first day of admission, then after the diagnosis of vasospasm is confirmed, Triple H therapy (hypertension, hypervolemia and hemodilution) will be started. norepnnephrine (0.01-0.2ug/kg/min) to mentain main arterial blood pressure >100mmhg and hypervolemia to maintain the CVP around 12---14 mmHg and hemodilution to maintain the haematocrit between 30% and 33%.

Drug: nimodipine

(60 mg/4 hours) orally or via nasogastric tube

Active Comparator: Milrinone group

The patients will receive oral Nimodipine (60 mg/4) will be given orally or in the gastric tube also from the first day of admission, then after the diagnosis of vasospasm is confirmed, start milrinone bolus of 0.1-0.2 mg/kg followed by 0.75mcg/k/min, if no response after 30min increase the infusion to 1-25mcg/kg/min with maintaining CVP 5:8. Norepinephrine (0.01-0.2ug/kg/min) is used only to restore the mean arterial pressure (MAP) to its previous values If there was no recurrence of symptoms after 72 h, we decreased the milrinone infusion by 0.25 mcg/kg/min every 24 or 48 h until discontinuation. If there are any recurrent of symptoms of vasospasm, the patients are placed back on the dose they were previously receiving. If required, another Milrinone bolus is administered if the patient's deficits do not revert12.

Drug: Oral Nimodipine and milrinone

Oral Nimodipine then after the diagnosis of vasospasm is confirmed, start milrinone bolus

Outcome Measures

Primary Outcome Measures

Concentration of transcutaneous cerebral mixed oxygen saturation [every 24 hours up to 1 week]
by forehead bilateral interconnected adhesive probes

Secondary Outcome Measures

Number of participants having cerebral infarction (cerebral infarction incidence) [every 48 hours up to 1 week]
detected by computed tomography
Number of participants restore of the previous conscious level and motor state(Percentage of drug success) [1 hour after administration of milrinone and 2 hours after administration of triple H therapy]
restore of the previous conscious level and motor state
value of Glasgow coma scale [every 24 hours up to total days of ICU and hospital stay]
with minimum scale vlue of 3 is the worst and maximum value of 16 indicate better outcome
Number of participants develop one of adverse events [after administration of the study drugs up to 30 days]
hypotension ,bradycardia,hypotesion
Total ICU and hospital stay [up to 30 days after administration of the study drugs]
mortality rate [30 day after administration of the study drugs]
Number of participants died within 30 day after administration of the study drugs
value of Modified Rankin scale [3,6,12 monthes after drug administration]
Level 0: no symptoms Level 1: no significant disability, despite symptoms; able to perform all usual duties and activities Level 2: slight disability unable to perform all previous activities but able to look after own affairs without assistance Level 3: moderate disability; requires some help, but able to walk without assistance. Level 4: moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance Level 5: sever disability; bedridden, incontinent and requires nursing care and attention
Glasgow Outcome Scale [3,6,12 monthes after drug administration]
1. Dead: As a direct result of brain trauma, or … due to secondary complications or other complications" "2. Vegetative State: Patients who remain unresponsive and speechless…." "3. Severe Disability: The The patient is conscious but needs the assistance of another person for some activities of daily living every day.…." "4. Moderate Disability: Such a patient is able to look after himself at home, to get out and about to the shops and to travel by public transport. However, some previous activities, either at work or in social life, are now no longer possible by reason of either physical or mental deficit…." "5. Good Recovery: This indicates the capacity to resume normal occupational and social activities, although there may be minor physical or mental deficits…social outcome should be included in the assessment here, such as leisure activities and family relationships..

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Adult patients admitted to our surgical ICU
aged between (18-60) years old
World Federation of Neurological Surgeons grades 1-3 Grades

Exclusion Criteria:

Aneurysmal SAH
SAH with Fisher Grade I and IV,
World Federation of Neurological Surgeons grade IV & V
No informed consent,
peripheral vascular disease
Cardiac disease (heart block, severe valvular stenosis, cardiomyopathothy , ejection fraction<40%), Renal impairment (serum creatinine ≥ 1.4 mg.L-1), Hemodynamic instability