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NCT Number: NCT07779486

High- vs Standard-Dose Intravenous Magnesium for Acute Headache

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.

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Key information

Conditions

Acute Headache Acute Pain Agnosia Brain Diseases Central Nervous System Diseases Cluster Headache Disease Attributes Emergencies Headache Disorders Headache Disorders, Primary Migraine Migraine Disorders Nervous System Diseases Neurobehavioral Manifestations Neurologic Manifestations Pain Pathologic Processes Pathological Conditions, Signs and Symptoms Perceptual Disorders Signs and Symptoms Tension-Type Headache Trigeminal Autonomic Cephalalgias

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

University Hospital Fattouma Bourguiba Monastir

Monastir, 5000, Tunisia

Location status: Recruiting

Location contact

Semir Nouira, Professor

CONTACT

[email protected]

73106046 ext. 00216

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

  • 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

Treatment and study plan

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 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.

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.

Primary outcomes

  1. Change in Pain Intensity at 60 Minutes

    Time frame: 60 minutes

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

  2. Proportion of Responders at 60 Minutes

    Time frame: 60 minutes

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

Secondary outcomes

  1. Pain Intensity Over Time

    Time frame: 0 to 120 minutes

    Area under the curve (AUC) of VAS pain scores measured from baseline to 120 minutes.

  2. Time to Clinically Meaningful Pain Relief

    Time frame: Up to 120 minutes

    Time from treatment administration to achievement of clinically meaningful pain relief, defined as VAS ≤3 or ≥50% reduction from baseline.

  3. Use of Rescue Medication

    Time frame: 30 to 120 minutes

    Proportion of participants requiring rescue analgesia after 30 minutes due to insufficient pain relief.

  4. Adverse Events

    Time frame: 0 to 120 minutes

    Incidence and type of treatment-emergent adverse events during the observation period.

Other outcomes

  1. Patient Satisfaction

    Time frame: 120 minutes

    Patient-reported satisfaction with treatment using a standardized scale.

  2. Association Between Ionized Magnesium and Treatment Response

    Time frame: Baseline to 60 minutes

    Relationship between baseline ionized magnesium levels and analgesic response at 60 minutes.

Study contacts

Contact information is provided by the study sponsor or research team.

Semir Nouira, Professor

CONTACT

[email protected]

73106046 ext. 00216

Sponsors and collaborators

Lead sponsor

University of Monastir

Other

Registry information

Official study title

Intravenous Magnesium Sulfate Versus Paracetamol for the Treatment of Acute Non-Traumatic Headache in the Emergency Department: A Randomized Double-Blind Controlled Trial

Acronym: MAGHEAD

Important dates

Study start
2026
Primary completion
2029
Study completion
2030
First posted
Aug 21, 2026
Registry last updated
Aug 21, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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