Milrinone Infusion for VAsospam Treatment in Subarachnoid hemoRrhage

NCT04362527 | Completed Phase 3 DMC

• 1 other identifier: 2019-002145-37
• Study Type: interventional
• Target: 370
• Locations: 1 country
• Sites: 16

Brief Summary

Subarachnoid hemorrhage (SAH) is a frequent and severe disease. Mortality can reach 40%. The most frequent complication of SAH is arterial vasospasm, with estimated incidence as high as 70%. Vasospasm is responsible for cerebral ischemia leading to severe morbidity, poorer quality of life and increased mortality. Intravenous Milrinone, because of vasodilatory properties could be a therapeutic option. We hypothesize that intravenous infusion of Milrinone will improve the neurological recovery of patients with vasospasm following aneurysmal SAH at 3 months. This is a Phase III, multi-center, randomized, double-blinded, placebo-controlled study. The primary outcome will be the proportion of patients with a good outcome 3 months (defined as a modified rankin score ≤2).

Conditions

Vasospasm

Keywords

Milrinone

Outcome Measures

Primary Outcomes (1)

• Proportion of patients with a good outcome at 3 months

  modified Rankin score ≤2 (0 = No symptoms, 1 = No significant disability. Able to carry out all usual activities, despite some symptoms, 2 = Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities, 3 = Moderate disability. Requires some help, but able to walk unassisted, 4 = Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted, 5 = Severe disability. Requires constant nursing care and attention, bedridden, incontinent, 6 = Death)

  3 months

Secondary Outcomes (12)

• Mortality rates in intensive care and in hospital

  up to 6 months

• Modified Rankin Score at 3 and 6 months

  3 and 6 months

• Glasgow outcome scale Extended at 3 and 6 months

  up to 6 months

• EQ-5D

  up to 6 months

• Evaluation of the radiologic effectiveness of the treatment

  up to 14 days

Study Arms (2)

Milrinone

EXPERIMENTAL

The patients randomized to this arm will have Milrinone (Laboratoires STRAGEN, France)

Drug: Milrinone 1 Mg/mL Solution for Injection

Placebo

PLACEBO COMPARATOR

The patients randomized to this arm will have Saline solution

Drug: Saline solution for injection

Interventions

Saline solution for injection DRUG

Blinding procedure will be set up for the administration of the treatment

Also known as: Sodium Chloride 0.9%

Placebo

Milrinone 1 Mg/mL Solution for Injection DRUG

Blinding procedure will be set up for the administration of the treatment

Also known as: Corotrope

Milrinone

Eligibility Criteria

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

You may qualify if:

• Adult patients hospitalized for aneurysmal SAH
• First episode of vasospasm, with a diagnosis confirmed on cerebral arterial CT-scanner
• Informed consent from a legal representative, or emergency procedure

You may not qualify if:

• Initial Glasgow score at 3 with a bilateral mydriasis
• Moribund patient
• Contraindication to Milrinone (notably obstructive cardiomyopathy…)
• Cerebral infarction in the vasospasm area already present on the CT-scanner at the time of diagnosis (lack of expected benefit of treatment in this case according to medical judgement)
• Cardiac failure requiring inotrope administration at the time of randomisation
• Uncontrolled elevated intra-cranial pressure (i.e. ICP\>25 mmHg for more than 20 minutes)
• Patient with flutter or cardiac arrhythmia (atrial fibrillation) poorly tolerated
• Major metabolic disturbance (uncorrected hypokalaemia \<3 mmol/L)
• Non-affiliation to French health care coverage,
• Pregnant, breastfeeding or parturient woman
• Adult deprived of their liberty by judicial or administrative decision
• Adult under compulsory psychiatric care
• Adult patient protected under the law (guardianship or trusteeship)

Sponsors & Collaborators

• University Hospital, Angers: lead

Study Sites (16)

CHU Angers

Angers, France

Location

CHU Besançon

Besançon, France

Location

CHU Bordeaux

Bordeaux, France

Location

CHU Brest

Brest, France

Location

CHU Caen

Caen, France

Location

Hôpital Gabriel Montpied

Clermont-Ferrand, France

Location

CHU Dijon

Dijon, France

Location

CHU Lille

Lille, France

Location

Hôpital Civils de Lyon

Lyon, France

Location

Hôpital Gui de Chauliac

Montpellier, France

Location

CHU Nantes

Nantes, France

Location

APHP Lariboisière

Paris, France

Location

Hôpital Fondation ROTHSCHILD

Paris, France

Location

CHU Rennes

Rennes, France

Location

Hôpital de Hautepierre

Strasbourg, 67098, France

Location

CHU Tours

Tours, France

Location

Related Publications (2)

• Lasocki S, Lakhal K, de Courson H, Geslain M, Launey Y, Pottecher J, Trouiller P, Laffon M, Gakuba C, Parot-Schinkel E, Hamel JF, Campfort M, Gaillard T; MiVAR study group; ATLANREA group; SFAR research network. Milrinone infusion for vasospasm treatment in subarachnoid haemorrhage: protocol for a double-blind randomised clinical trial - the MiVAR study. BMJ Open. 2025 Oct 28;15(10):e101483. doi: 10.1136/bmjopen-2025-101483.

  PMID: 41151960 DERIVED

• Lasocki S, Bruckert V, Campfort M, Leger M, Rineau E. Restrictive transfusion targets the heart now! Insight from the REALITY study. Anaesth Crit Care Pain Med. 2021 Apr;40(2):100854. doi: 10.1016/j.accpm.2021.100854. Epub 2021 Mar 27. No abstract available.

  PMID: 33781988 DERIVED

Related Links

• Related Info

MeSH Terms

Interventions

Milrinone; Solutions; Injections; Saline Solution; Sodium Chloride

Intervention Hierarchy (Ancestors)

Amrinone; Aminopyridines; Amines; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pharmaceutical Preparations; Drug Administration Routes; Drug Therapy; Therapeutics; Crystalloid Solutions; Isotonic Solutions; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Karim KL LAKHAL, PH

  University Hospital of Nantes

  PRINCIPAL INVESTIGATOR

• Olivier OH HUET, PU-PH

  Cavale Blanche - University Hospital of Brest

  PRINCIPAL INVESTIGATOR

• Pierre-François PP PERRIGAULT, PU-PH

  Hôpital Gui de Chauliac - University Hospital of Montpellier

  PRINCIPAL INVESTIGATOR

• Julien JP POTTECHER, PU-PH

  Hôpital de Hautepierre, University Hospital of Strasbourg

  PRINCIPAL INVESTIGATOR

• Russel RC CHABANNE, PH

  Hôpital Gabriel Montpied, University Hospital of Clermont-Ferrand

  PRINCIPAL INVESTIGATOR

• Benjamin BC Chousterman, PH

  Hôpital Lariboisière, Paris (AP-HP)

  PRINCIPAL INVESTIGATOR

• Marc ML Laffon, PU-PH

  Hôpital Bretonneau - University Hospital of Tours

  PRINCIPAL INVESTIGATOR

• Yoann YL Launey, PH

  University Hospital of Rennes

  PRINCIPAL INVESTIGATOR

• Claire CD Dahyot Fizelier, PU-PH

  University Hospital of Poitiers

  PRINCIPAL INVESTIGATOR

• Belaid BB Bouhemad, PU-PH

  University Hospital of Dijon

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: Phase 3, multicenter, international (France, Switzerland), randomized, double blinded, placebo-controlled study

Study Record Dates

• First Submitted: April 9, 2020
• First Posted: April 27, 2020
• Study Start: August 10, 2020
• Primary Completion: October 11, 2025
• Study Completion: January 12, 2026
• Last Updated: March 9, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: The data will be shared after signing a negotiated data transfer contract (data access agreement), for the duration indicated in the contract.
• Access Criteria: The data will be made available via secure transfer (sharing platform validated by Angers CHU: BlueFiles or Oodrive).

Locations

FR (16)