MMA Infusion of Lidocaine for Treatment of Headache in Patients With Aneurysmal SAH (MIL-SAH)

Middle Meningeal Artery Infusion of Lidocaine for Treatment of Headache in Patients With Aneurysmal Subarachnoid Hemorrhage

The purpose of the MIL-SAH trial is to evaluate the efficacy and safety of middle meningeal artery (MMA) lidocaine infusion for the treatment of headache in patients with aneurysmal subarachnoid hemorrhage (SAH). The trial aims to determine whether MMA lidocaine infusion reduces headache severity during the first 72 hours following endovascular aneurysm treatment compared with placebo.

Study Overview

• Status: Not yet recruiting
• Conditions: Headaches Associated With Subarachnoid Hemorrhage (SAH)
• Intervention / Treatment: Drug: Lidocaine hydrochloride; Drug: Isotonic saline

Detailed Description

The MIL-SAH trial is a multicenter, randomized, double-blind, placebo-controlled clinical trial evaluating whether middle meningeal artery (MMA) infusion of lidocaine reduces headache severity in patients with aneurysmal subarachnoid hemorrhage (SAH). Adult patients with SAH undergoing endovascular aneurysm treatment are randomized to receive either bilateral MMA lidocaine infusion or placebo immediately after successful aneurysm securement.

SAH-related headaches are frequently severe, persistent, and difficult to control with current analgesic strategies, which often rely on opioids. Preliminary case series have suggested that MMA lidocaine infusion may reduce headache severity with few adverse effects, but randomized clinical trials to support this is currently lacking. This trial aims to provide robust data on the efficacy and safety of this novel treatment approach.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Rasmus H Dahl; Phone Number: 0045 35456491; Email: rasmus.holmboe.dahl@regionh.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria

1. Age ≥ 18 years
2. Imaging showing a SAH and intracranial aneurysm
3. Undergo endovascular therapy within 72 hours*
4. Glasgow coma scale (GCS) score of 14-15

5. Maximum headache severity of NRS score ≥ 4 at a time > 1 hour after ictus or the ad-ministration of opioids due to headache

   Exclusion criteria

6. The patient is unable to understand information provided in the national language or English
7. Known allergies to amide-type local anesthetics or iodinated contrast media
8. Pregnancy or lactation
9. Severe hepatic impairment
10. History of epilepsy
11. History of chronic opioid use
12. Renal impairment with eGFR < 30 mL/min/1.73m2
13. Current treatment with class III antiarrhythmics (e.g. amiodarone)
14. Atrioventricular block of II and III degree
15. Unsuccessful endovascular aneurysm securement or procedural complications

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MMA lidocaine; The participants will receive 50 mg of lidocaine in each middle meningeal artery	Drug: Lidocaine hydrochloride; Participants will receive lidocaine hydrochloride at a dose of 50 mg per side (10 mg/mL; 5 mL). The infusion is delivered into each MMA over 5 minutes by manual injection, resulting in a total injection time of approximately 10 minutes and a total lidocaine hydrochloride dose of 100 mg. The trial intervention is performed only during the endovascular treatment session. There is no repeated dosing of trial medication.
Placebo Comparator: MMA isotonic saline; The participants will receive isotonic saline in each middle meningeal artery	Drug: Isotonic saline; Participants will receive 5 mL of isotonic saline per side. The infusion is delivered into each MMA over 5 minutes by manual injection, resulting in a total injection time of approximately 10 minutes. The trial intervention is performed only during the endovascular treatment session. There is no repeated dosing of trial medication.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Headache Severity	Daily maximum headache severity over the first 72 hours following the trial intervention	From 0 to 72 hours postprocedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Headache relief	Proportion of participants with headache relief (none to mild headache, NRS≤3) at 2 hours following the trial intervention	From baseline to 2 hours postprocedure
Opioid consumption	Total opioid consumption (oral morphine equivalents) during the first 72 hours following the trial intervention	From 0-72 hours postprocedure
Patient global assessment	Patient global assessment (PGA) score at 72 hours following the trial intervention. Participants will be asked to respond to the question, "Overall, how do you feel about your level of headache control since the treatment?" using a 5-point scale (poor, fair, good, very good, or excellent).	From 0 to 72 hours postprocedure
Adverse Events Related to Intraarterial Lidocaine Injection	Proportion of participants with new onset of facial paresis, facial numbness, diplopia, blurry vision, or dizziness during the first 24 hours following the trial intervention	From 0 to 24 hours postprocedure

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): February 1, 2030

Study Registration Dates

• First Submitted: September 7, 2026
• First Submitted That Met QC Criteria: September 7, 2026
• First Posted (Actual): September 11, 2026

Study Record Updates

• Last Update Posted (Actual): September 11, 2026
• Last Update Submitted That Met QC Criteria: September 7, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: lidocaine; SAH; subarachnoid hemorrhage; headache; middle meningeal artery; MMA
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Hemorrhage; Intracranial Hemorrhages; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Headache; Subarachnoid Hemorrhage; Organic Chemicals; Anilides; Amides; Aniline Compounds; Amines; Acetanilides; Inorganic Chemicals; Chlorine Compounds; Sodium Compounds; Chlorides; Hydrochloric Acid; Lidocaine; Sodium Chloride
• Other Study ID Numbers: p-2026-22097; E-24086-04 (Other Grant/Funding Number: Copenhagen University Hospital - Rigshospitalet); Pilot Research Grant (Other Grant/Funding Number: European Society of Minimally Invasive Neurological Therapy); 2026-526092-36-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No