Safety of Intravenous Milrinone for the Treatment of Subarachnoid Hemorrhage-induced Vasospasm (MilriSpasm)

The aim of this study is to evaluate the tolerance of intravenous milrinone combined to the current standard treatment for cerebral vasospasm following subarachnoid hemorrhage. Assessment of IV milrinone safety in this setting is mandatory before the conduction of a large study assessing its effectiveness.

Study Overview

• Status: Completed
• Conditions: Subarachnoid Hemorrhage; Cerebral Vasospasm
• Intervention / Treatment: Other: Rhythmic tolerance; Other: Hematological tolerance; Other: Milrinone efficiency on cerebral vasospasm; Other: Milrinone efficiency using the modified Rankin scale

Detailed Description

The aim of this prospective observational study is to evaluate the hemodynamic tolerance of intravenous milrinone for the treatment of arterial vasospasm following subarachnoid hemorrhage. Intravenous milrinone is part of our standard care protocol for the management of cerebral vasospasm in association with nimodipine (intravenous or enteral route) and high arterial blood pressure (mean arterial pressure of 100-120 mmHg, spontaneously or induced by volume expansion and norepinephrine). All patients of our ICU who were diagnosed with cerebral arterial vasospasm during the few days following a subarachnoid hemorrhage will be included.

• Study Type: Observational
• Enrollment (Actual): 60

Contacts and Locations

Study Locations

• France
  • Nantes, France, 44000
    • CHU Nantes

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Primary Purpose: Treatment Study Phase: NA Intervention Model: Single group Number of Arms: 1 Masking: Open label Allocation: NA Study Endpoint Classification: Safety Enrollment: 60 participants

Description

Inclusion Criteria:

• Subjects 18 years
• Hospitalized in our intensive care unit
• Subarachnoid hemorrhage proven on CT angiogram
• Cerebral vasospasm proven on CT angiogram

Exclusion Criteria:

• Pregnant women
• Minor
• Major under guardianship

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemodynamic tolerance during treatment: defined by a stable mean blood pressure of 100-120	A good hemodynamic tolerance is defined by a stable mean blood pressure of 100-120 mmHg without neither the need to decrease milrinone infusion rate below 0.5 g.kg-1.min-1 nor the need to increase norepinephrine above 1g.kg-1.min-1 Safety Issue: No	At 6 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rhythmic tolerance: defined by the occurrence of arrhythmia prompting the initiation of	Rhythmic intolerance is defined by the occurrence of arrhythmia prompting the initiation of an antiarrhythmic medication and the need to decrease or even to stop the infusion of milrinone Safety Issue: No	Rhythmic tolerance will be assessed for the duration of treatment, which will be on average one month.Heart rate and rhythm will be measured continuously, but assessed for fluctuation outside the reference range daily (during the length of treatment).
Hematological tolerance: will be considered good if milrinone infusion was not interrupted	Hematological tolerance will be considered good if milrinone infusion was not interrupted owing to the occurrence of thrombocytopenia Safety Issue: No	Hematological tolerance will be assessed daily through measuring platelet count for the duration of treatment.
Milrinone efficiency on cerebral vasospasm	It will be assessed using ultrasound measurements of middle cerebral arteries velocities. A decrease of at least 20% of the mean velocity or of the Lindegaard index will be considered as a significant positive effect of the treatment (including milrinone). Safety Issue: No	Milrinone efficiency on cerebral vasospasm will be assessed for the duration of treatment, which will be on average one month. Mean velocity and the lindegard index will be initially measured at 0, 2, 12 and 24 hours; and subsequently daily.
Milrinone efficiency on patient-centered neurological outcome using the modified Rankin scale	Scored as follows: 0 = No symptoms, 1 = No significant disability. Able to perform all usual activities, despite certain symptoms, 2= Slight disability. Able to take care of his own affairs without assistance, but unable to carry out all previous activities, 3 = Moderate disability. Requires some help, but able to walk unassisted, 4 = Moderate severe disability. Unable to meet their own physical needs without help and unable to walk without help, 5 Severe disability. Needs constant care and attention, bedridden, incontinent, 6 = Death. Safety Issue: No	At 6 months.

Collaborators and Investigators

• Sponsor: Nantes University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2020
• Primary Completion (Actual): August 31, 2020
• Study Completion (Actual): August 31, 2020

Study Registration Dates

• First Submitted: April 23, 2018
• First Submitted That Met QC Criteria: May 4, 2018
• First Posted (Actual): May 7, 2018

Study Record Updates

• Last Update Posted (Actual): March 3, 2022
• Last Update Submitted That Met QC Criteria: March 2, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Subarachnoid hemorrhage; Cerebral vasospasm; Milrinone; Hemodynamic tolerance
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Intracranial Hemorrhages; Hemorrhage; Subarachnoid Hemorrhage; Vasospasm, Intracranial; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Protective Agents; Cardiotonic Agents; Phosphodiesterase Inhibitors; Phosphodiesterase 3 Inhibitors; Milrinone
• Other Study ID Numbers: RC17_0451

Drug and device information, study documents

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