High- vs Standard-Dose Intravenous Magnesium for Acute Headache

NCT07779486 | Recruiting

• 1 other identifier: MAGHEAD_study
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

Headache is one of the most common reasons for consultation in emergency departments and represents a significant cause of disability, particularly in patients with migraine and other primary headache disorders. Despite the availability of several analgesic treatments, including nonsteroidal anti-inflammatory drugs and paracetamol, pain relief is often incomplete, and a proportion of patients require additional rescue therapy. Magnesium sulfate has emerged as a potential therapeutic option in acute headache due to its role in modulating neuronal excitability, vascular tone, and pain-related neurotransmitter release. However, its efficacy as a standalone treatment, the optimal intravenous dose, and its comparative effectiveness versus standard therapy remain unclear. This randomized, double-blind, controlled trial aims to evaluate the efficacy and safety of intravenous magnesium sulfate in the treatment of acute non-traumatic headache in the emergency department. Participants will be randomly assigned to receive either low-dose magnesium sulfate (2 g IV), high-dose magnesium sulfate (4 g IV), or intravenous paracetamol (1 g IV) as an active comparator. The primary outcome is the change in pain intensity measured using the Visual Analog Scale (VAS) at 60 minutes after treatment administration, as well as the proportion of patients achieving at least 50% pain reduction. Secondary outcomes include time course of pain relief, need for rescue medication, adverse events, patient satisfaction, and length of stay in the emergency department. In addition, the study will assess baseline ionized magnesium levels to explore their relationship with treatment response and evaluate whether magnesium levels may predict clinical efficacy. The results of this study may help clarify the role of intravenous magnesium sulfate in the management of acute headache and potentially improve treatment strategies in emergency settings.

Conditions

Acute Headache; Migraine; Tension-type Headache; Cluster Headache

Keywords

Acute headache; Migraine; Emergency department; Intravenous magnesium Magnesium sulfate; Paracetamol; Acute pain; Analgesia

Outcome Measures

Primary Outcomes (2)

• Change in Pain Intensity at 60 Minutes

  Change in pain intensity measured using the Visual Analog Scale (VAS, 0-10) from baseline to 60 minutes after treatment administration

  60 minutes

• Proportion of Responders at 60 Minutes

  Proportion of participants achieving a ≥50% reduction in VAS pain score from baseline at 60 minutes.

  60 minutes

Secondary Outcomes (4)

• Pain Intensity Over Time

  0 to 120 minutes

• Time to Clinically Meaningful Pain Relief

  Up to 120 minutes

• Use of Rescue Medication

  30 to 120 minutes

• Adverse Events

  0 to 120 minutes

Other Outcomes (2)

• Patient Satisfaction

  120 minutes

• Association Between Ionized Magnesium and Treatment Response

  Baseline to 60 minutes

Study Arms (3)

Magnesium Sulfate 2 g IV

ACTIVE COMPARATOR

Intravenous magnesium sulfate administered as a single dose of 2 g diluted in 100 mL of 0.9% sodium chloride over 10-15 minutes.

Drug: Magnesium Sulfate 2 grams

Magnesium Sulfate 4 g IV

ACTIVE COMPARATOR

Intravenous magnesium sulfate administered as a single dose of 4 g diluted in 100 mL of 0.9% sodium chloride over 10-15 minutes.

Drug: Magnesium Sulfate 4 G

Paracetamol 1 g IV

ACTIVE COMPARATOR

Intravenous paracetamol 1 g diluted in 100 mL, administered over 10-15 minutes.

Drug: Paracetamol 1 g

Interventions

Magnesium Sulfate 2 grams DRUG

Participants assigned to this arm will receive intravenous magnesium sulfate 2 g diluted in 100 mL of 0.9% sodium chloride administered over 10-15 minutes, along with a matching placebo for paracetamol. Infusions will be prepared in identical formats to maintain blinding. Continuous monitoring of vital signs will be performed during and after administration. Rescue medication may be administered from 30 minutes if predefined criteria are met.

Magnesium Sulfate 2 g IV

Magnesium Sulfate 4 G DRUG

Participants assigned to this arm will receive intravenous magnesium sulfate 4 g diluted in 100 mL of 0.9% sodium chloride administered over 10-15 minutes, along with a matching placebo for paracetamol.. Infusions will be prepared in identical formats to maintain blinding. Continuous monitoring of vital signs will be performed during and after administration. Rescue medication may be administered from 30 minutes if predefined criteria are met.

Magnesium Sulfate 4 g IV

Paracetamol 1 g DRUG

Participants assigned to this arm will receive intravenous paracetamol 1 g administered over 10-15 minutes, along with a matching placebo for magnesium (100 mL of 0.9% sodium chloride). Infusions will be prepared in identical formats to maintain blinding. Continuous monitoring of vital signs will be performed during and after administration. Rescue medication may be administered from 30 minutes if predefined criteria are met.

Paracetamol 1 g IV

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years
• Presentation to the emergency department with acute non-traumatic headache of less than 72 hours duration
• Diagnosis consistent with a primary headache disorder, including:
• Migraine
• Tension-type headache
• Cluster headache (according to ICHD-3 criteria)
• Moderate to severe pain intensity (VAS ≥5/10)
• Ability to understand the study procedures and provide informed consent

You may not qualify if:

• Suspected or confirmed secondary headache (e.g., intracranial hemorrhage, infection, mass lesion)
• Recent head trauma
• Known hypersensitivity or contraindication to magnesium sulfate or paracetamol
• Use of analgesic medication within the previous 6 hours
• Pregnancy or breastfeeding
• Severe renal insufficiency or conditions contraindicating magnesium administration
• Hemodynamic instability or clinically significant cardiac conduction disorders Prior participation in this study

Sponsors & Collaborators

• University of Monastir: lead

Study Sites (1)

University Hospital Fattouma Bourguiba Monastir

Monastir, 5000, Tunisia

RECRUITING

MeSH Terms

Conditions

Migraine Disorders; Tension-Type Headache; Cluster Headache; Emergencies; Acute Pain; Agnosia

Interventions

Magnesium Sulfate; Acetaminophen

Condition Hierarchy (Ancestors)

Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Trigeminal Autonomic Cephalalgias; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms; Perceptual Disorders; Neurobehavioral Manifestations

Intervention Hierarchy (Ancestors)

Magnesium Compounds; Inorganic Chemicals; Sulfates; Sulfuric Acids; Sulfur Acids; Sulfur Compounds; Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

Central Study Contacts

Semir Nouira, Professor

CONTACT

73106046; semir.nouira@rns.tn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 19, 2026
• First Posted: August 21, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2030
• Last Updated: August 21, 2026

Record last verified: 2026-08

Locations

TU (1)