Cerebral hemodynamic optimization by milrinone for the prevention of delayed cerebral ischemia in severe subarachnoid hemorrhage

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Toulouse

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

12 May 2026 → ongoing

Decision date (initial)

2024-09-16

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-513410-35-00

EudraCT number

2019-000509-58

ClinicalTrials.gov

NCT04282629

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Prophylaxis, Efficacy

The main objective is to evaluate, in patients with 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 and MedDRA coding

aneurysmal subarachnoid hemorrhage

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. - patients with severe SAHa (WFNS IV and V)
2. - absence of pre-existing neurological handicap (mRS 0-2)
3. - major patient (≥ 18 years)
4. - affiliation to social security or benefiting through a third person
5. - free patient, without tutorship or curatorship or under judicial protection
6. - obtaining a signed informed consent by a relative (or the person of trust) after clear and fair information about the study.

Exclusion criteria 15

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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary outcome is the volume of DCI lesions measured on a CT scan at 1 month

Secondary endpoints 9

1. → Radiological parameters on CT at 1 month: -percentage of patients with DCI
2. → Evolution in intensive care: •Neurological complications: -number of episodes of PtiO2 below the ischemic threshold in intensive care: PtiO2 <20 mmHg (moderate hypoxia) and <15mmHg (severe hypoxia) for at least 15 minutes; - total duration of episodes of PtiO2 <20mmHg (moderate hypoxia) and <15mmHg (severe hypoxia) -number of recourse to an endovascular treatment -intracranial hypertension in intensive care: ICP> 20 mmHg for at least 15 minutes.
3. Evolution in intensive care: • Number and type of non-neurological complications
4. → Evolution in intensive care: • Variation in general and cerebral hemodynamics (HR, MAP, ICP, CPP, transcranial Doppler velocity) with transthoracic cardiac ultrasound (TTE) cardiac output or pulse-wave contour study with transpulmonary thermodilution (PICCO) ®)
5. → Evolution in intensive care: • Number of days in intensive care
6. → Evolution in intensive care: • Number of days with mechanical ventilation
7. → Prognosis: - neurological prognosis at 1 month, 3 months, 6 months and 1 year evaluated by the modified Rankin score (good prognosis: mRS 0, 1 and 2 / poor prognosis: mRS 3, 4 and 5) and the Glasgow Outcome Scale extended (good outcome: GOSE 5 to 8 / poor outcome: GOSE 1 to 4).- Sickness Impact Profile (SIP-65) quality-oflife scale at 3 months, 6 months and 1 year. - Mortality at 1 month, 3 months, 6 months and 1 year - number of days of hospitalization
8. → Number of adverse events
9. → Build up a biocollection for the evaluation of plasma brain biomarkers or other potential biomarkers

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Toulouse

Sponsor organisation

Centre Hospitalier Universitaire De Toulouse

Address

2 Rue Viguerie

City

Toulouse

Postcode

31300

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Toulouse

Contact name

principal investigator

Public contact point

Organisation

Centre Hospitalier Universitaire De Toulouse

Contact name

clinical research project manager

Locations

1 EU/EEA country · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications