Acute Headache, Cluster Headache, Migraine, Tension-type Headache
Conditions
Keywords
Acute headache, Migraine, Emergency department, Intravenous magnesium Magnesium sulfate, Paracetamol, Acute pain, Analgesia
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.
Interventions
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.
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.
DRUGParacetamol 1 g
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.
Sponsors
University of Monastir
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Pain Intensity at 60 Minutes | 60 minutes | Change in pain intensity measured using the Visual Analog Scale (VAS, 0-10) from baseline to 60 minutes after treatment administration |
| Proportion of Responders at 60 Minutes | 60 minutes | Proportion of participants achieving a ≥50% reduction in VAS pain score from baseline at 60 minutes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pain Intensity Over Time | 0 to 120 minutes | Area under the curve (AUC) of VAS pain scores measured from baseline to 120 minutes. |
| Time to Clinically Meaningful Pain Relief | Up to 120 minutes | Time from treatment administration to achievement of clinically meaningful pain relief, defined as VAS ≤3 or ≥50% reduction from baseline. |
| Use of Rescue Medication | 30 to 120 minutes | Proportion of participants requiring rescue analgesia after 30 minutes due to insufficient pain relief. |
| Adverse Events | 0 to 120 minutes | Incidence and type of treatment-emergent adverse events during the observation period. |
Countries
Tunisia
Contacts
CONTACTSemir Nouira, Professor
Outcome results
None listed