Cerebral Hemodynamic Optimization by Milrinone to Prevent Delayed Cerebral Ischemia

NCT04282629 | Recruiting Phase 2 DMC

• 1 other identifier: RC31/18/0472
• Study Type: interventional
• Target: 234
• Locations: 1 country
• Sites: 5

Brief Summary

The present study is a randomized, multi-center, double-blind, prospective study that tests the efficacy of intravenous milrinone to optimize cerebral hemodynamic and prevent delayed cerebral ischemia (DCI) during the high-risk period (day 4- day 14) in patients with severe subarachnoid hemorrhage due to intracranial aneurysm rupture (SAHa) (WFNS IV-V). The main objective is to evaluate, in comatose patients and / or sedated on D3 following a severe SAHa (WFNS IV -V), the effect of 10 days of milrinone versus placebo, in addition to the usual management, on the volume of DCI lesions measured on CT scan at 1 month.

Conditions

Aneurysmal Subarachnoid Hemorrhage

Keywords

Milrinone; Vasospasm; Delayed Cerebral Ischemia

Outcome Measures

Primary Outcomes (1)

• volume of delayed cerebral ischemia lesions

  volume of DCI lesions measured on CT scan and validated by Magnetic Resonance Imaging (MRI) imaging at 1 month

  1 month

Secondary Outcomes (21)

• Radiological parameters on CT at 1 month

  1 month

• Evolution in intensive care: Neurological complications 1

  1 month

• Evolution in intensive care: Neurological complications 2

  1 month

• Evolution in intensive care: Neurological complications 3

  1 month

• Evolution in intensive care: Neurological complications 4

  1 month

Study Arms (2)

Milrinone

EXPERIMENTAL

"milrinone" group benefiting from an identical treatment to the standard care group and in addition, administration of milrinone (0.75 μg / kg / min, intravenous) from Day 4 to Day 14. In case of suspicion of vasospasm and after ineffective effect of medical measures (euvolemia and increase in mean arterial pressure), an endovascular treatment will be possible. The occurrence of vasospasm will be monitored closely with clinical examination and cerebral tissue oxygen pressure (PtiO2). From D4 to D14, general and biological data, clinical examination will be collected daily. Intensive care unit complications (neurologic, pulmonary, cardiac and septic complications) will be collected. At 1 month, the volume of DCI lesions will be measured on CT scan. Neurologic prognosis, quality of life and mortality will be studied at 1 month, 3 month, 6 month and 1 year. Adverse events will be monitored closely.

Drug: Milrinone Injection

Standard Care

PLACEBO COMPARATOR

The standard care group will follow the recommended management of SAHa and will receive a placebo (intravenous glucose 5%) from Day 4 to Day 14. In case of suspicion of vasospasm and after ineffective effect of medical measures (euvolemia and increase in mean arterial pressure), an endovascular treatment will be possible. The occurrence of vasospasm will be monitored closely with clinical examination and cerebral tissue oxygen pressure (PtiO2). From D4 to D14, general and biological data, clinical examination will be collected daily. Intensive care unit complications (neurologic, pulmonary, cardiac and septic complications) will be collected. At 1 month, the volume of DCI lesions will be measured on CT scan. Neurologic prognosis, quality of life and mortality will be studied at 1 month, 3 month, 6 month and 1 year. Adverse events will be monitored closely.

Other: Placebo

Interventions

Milrinone Injection DRUG

administration of milrinone (0.75 μg / kg / min, intravenous) from Day 4 to Day 14

Milrinone

Placebo OTHER

administration of placebo (intravenous glucose 5%) from Day 4 to Day 14

Standard Care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• patients with severe SAHa (WFNS IV and V,) whose neurological examination is impossible because of coma (Glasgow coma score of 8 or less) or need for sedation at D3
• absence of pre-existing neurological handicap (mRS 0-2)
• major patient (≥ 18 years)
• affiliation to social security or benefiting through a third person
• free patient, without tutorship or curatorship or under judicial protection
• obtaining a signed informed consent by a relative (or the person of trust) after clear and fair information about the study.

You may not qualify if:

• patients with non-severe SAHa (WFNS I, II and III)
• Occurrence of a major complication (haemorrhagic or ischaemic) documented during the procedure of securing the aneurysm and endangering the short-term vital prognosis
• heart failure requiring inotropic administration at the time of randomization
• ICHT at the time of randomisation (ICP\> 25 mmHg for at least 20 min)
• known severe obstructive heart diseases
• flutter patient or atrial fibrillation
• hypotension and / or severe hypovolemia with hemodynamic instability
• septic shock
• acute / chronic renal insufficiency (Cl \<50ml / min)
• major hydroelectrolytic disorders (hypokalemia \<3 mmol / L)
• known hypersensitivity to milrinone or any of the excipients
• early limitation of life-sustaining care
• pregnancy, breastfeeding
• permanent contraindications to MRI
• participation in another clinical interventional study

Sponsors & Collaborators

• University Hospital, Toulouse: lead

Study Sites (5)

University Hospital Bordeaux

Bordeaux, France

ACTIVE NOT RECRUITING

CHUGA

Grenoble, France

ACTIVE NOT RECRUITING

University Hospital of La Réunion

La Réunion, France

RECRUITING

HCL

Lyon, France

RECRUITING

University Hospital of Toulouse

Toulouse, France

RECRUITING

MeSH Terms

Conditions

Subarachnoid Hemorrhage

Interventions

Milrinone

Condition Hierarchy (Ancestors)

Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Amrinone; Aminopyridines; Amines; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Thomas Geeraerts, MD PhD

  University Hospital, Toulouse

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Thomas Geeraerts, MD PhD

CONTACT

056-177-2100; geeraerts.t@chu-toulouse.fr

Nadera AINAOUI

CONTACT

056-177-2498; nadera.ainaoui@inserm.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Group milrinone versus group placebo

Study Record Dates

• First Submitted: February 17, 2020
• First Posted: February 25, 2020
• Study Start: July 25, 2021
• Primary Completion: July 1, 2025
• Study Completion: July 1, 2025
• Last Updated: September 25, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (5)