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Clinical Trials/NCT05131867
NCT05131867
Completed
Phase 2

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

Zagazig University2 sites in 1 country30 target enrollmentStarted: November 24, 2021Last updated:

Overview

Phase
Phase 2
Status
Completed
Enrollment
30
Locations
2
Primary Endpoint
Concentration of transcutaneous cerebral mixed oxygen saturation

Overview

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.

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
Allocation
Randomized
Intervention Model
Parallel
Primary Purpose
Treatment
Masking
Double (Participant, Investigator)

Masking Description

double

Eligibility Criteria

Ages
18 Years to 60 Years (Adult)
Sex
All
Accepts Healthy Volunteers
No

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

Arms & Interventions

triple H group

Active Comparator

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%.

Intervention: nimodipine (Drug)

Milrinone group

Active Comparator

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.

Intervention: Oral Nimodipine and milrinone (Drug)

Outcomes

Primary Outcomes

Concentration of transcutaneous cerebral mixed oxygen saturation

Time Frame: every 24 hours up to 1 week

by forehead bilateral interconnected adhesive probes

Secondary Outcomes

  • 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)
  • value of Modified Rankin scale(3,6,12 monthes after drug administration)
  • Number of participants develop one of adverse events(after administration of the study drugs up to 30 days)
  • 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)
  • Glasgow Outcome Scale(3,6,12 monthes after drug administration)
  • value of Glasgow coma scale(every 24 hours up to total days of ICU and hospital stay)
  • Number of participants having cerebral infarction (cerebral infarction incidence)(every 48 hours up to 1 week)

Investigators

Sponsor Class
Other Gov
Responsible Party
Principal Investigator
Principal Investigator

Marwa Mohamed Medhat

lecture of anesthesia and surgical intensive care (Principal Investigator)

Zagazig University

Study Sites (2)

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