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Zolmitriptan 042 Trial

A randomized, double-blind, placebo-controlled trial of zolmitriptan 2.5 mg for the acute treatment of migraine

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Year of Publication: 1997

Authors: Dowson AJ, Massiou H, Lainez JM, ..., Ferrari MD

Journal: Neurology

Citation: Neurology. 1997;49(5):1210–1214. doi:10.1212/WNL.49.5.1210

Link: https://www.neurology.org/doi/10.1212/wn...ub%20%200pubmed

PDF: https://www.neurology.org/doi/pdfdirect/...2/WNL.49.5.1219

Clinical Question

Is a single 2.5 mg oral dose of zolmitriptan effective and safe for acute migraine treatment compared with placebo?

Bottom Line

Zolmitriptan 2.5 mg provided significantly greater headache relief and pain freedom at 2 and 4 hours compared to placebo, with a favorable safety profile.

        Major Points
        327 patients randomized 2:1 to zolmitriptan 2.5 mg or placebo for a single migraine attack
Headache response at 2 hours was significantly greater with zolmitriptan (62% vs 36%)
38% achieved pain freedom at 4 hours with zolmitriptan vs 13% with placebo
Adverse events were mild; most commonly nausea, dizziness, somnolence
No serious adverse events or significant ECG/lab abnormalities reported

      

Design

Study Type: Randomized, double-blind, placebo-controlled trial

Randomization: 1

Blinding: Double-blind (participants, investigators, outcome assessors)

Enrollment Period: Not specified (prior to 1997)

Follow-up Duration: 4 hours post-dose (single migraine attack)

Centers: 38

Countries: Multiple EU countries

Sample Size: 327

Analysis: Intention-to-treat; chi-square tests for categorical variables; ANCOVA for continuous outcomes

Inclusion Criteria

Age 12–65 years
History of migraine (with or without aura) for ≥1 year
1–6 migraine attacks/month
Onset before age 50
Moderate to severe migraine at time of treatment

Exclusion Criteria

Other significant medical conditions (e.g., uncontrolled hypertension, CAD)
Basilar or hemiplegic migraine
Pregnancy or breastfeeding
Use of ergotamines or other triptans within 24h
History of medication overuse

Baseline Characteristics

Characteristic	Zolmitriptan 2.5 mg	Placebo
Mean Age (years)	40.7 +/- 11.26	40.2 +/- 11.84
Female (%)	85	85
Male (%)	15	15
Mean Age of Migraine Onset (years)	21 +/- 10.24	21 +/- 10.61
Migraine with Aura (%)	7	5
Migraine without Aura (%)	69	70
Both Aura Types (%)	25	25
Migraines per Month	2.9 +/- 1.38	2.9 +/- 1.36
Hours of Work Missed per Migraine	4.0 +/- 4.46	4.0 +/- 5.45
Baseline Photophobia (%)	79	79
Baseline Phonophobia (%)	72	72
Baseline Nausea (%)	50	50
Baseline Moderate Headache (%)	76	76
Aura Preceding Treated Attack (%)	18	18
Headache on Awakening (%)	48	48

Arms

Field	Zolmitriptan 2.5 mg	Control
Intervention	Single oral dose of zolmitriptan 2.5 mg at onset of moderate or severe migraine	Matching placebo tablet
Duration	Single use	Single use

Outcomes

Outcome	Type	Control	Intervention	HR / OR / RR	P-value
Headache response at 2 hours (moderate/severe → mild/none)	Primary	36%	62%	4	<0.001
Pain freedom at 4 hours	Secondary	13%	38%		<0.001
Sustained pain freedom (2–24h)	Secondary	10%	31%		<0.001
Use of rescue medication	Secondary	48%	24%		<0.001
Nausea	Adverse	6%	11%		NS
Dizziness	Adverse	3%	9%		NS
Somnolence	Adverse	2%	8%		NS
Serious Adverse Events	Adverse	0	0

Subgroup Analysis

No formal subgroup analyses reported

Criticisms

Short follow-up (only single-attack, 4-hour evaluation)
Lack of active comparator (e.g., other triptans)
Majority of participants were women, limiting generalizability
Excludes patients with frequent or chronic migraine

Funding

Sponsored by AstraZeneca (developer of zolmitriptan)

Based on: Zolmitriptan 042 Trial (Neurology, 1997)

Authors: Dowson AJ, Massiou H, Lainez JM, ..., Ferrari MD

Citation: Neurology. 1997;49(5):1210–1214. doi:10.1212/WNL.49.5.1210

Content summarized and formatted by NeuroTrials.ai.

Zolmitriptan 042 Trial

(1997)

Objective

Zolmitriptan - To evaluate the efficacy and safety of a single 2.5 mg oral dose of zolmitriptan compared to placebo for the acute treatment of moderate or severe migraine.

Study Summary

• Zolmitriptan 2.5 mg significantly improved headache response at 2h vs placebo (62% vs 36%)
• Pain-free rate at 4h was 38% for zolmitriptan vs 13% for placebo
• No serious adverse events; nausea and dizziness were most common side effects

Intervention

327 patients randomized 2:1 to zolmitriptan 2.5 mg or placebo to treat a single migraine attack; outcomes assessed at 1, 2, and 4 hours; follow-up included labs and ECGs.

Inclusion Criteria

• Age 12–65
• Migraine with or without aura >1 year
• 1–6 migraines/month
• Onset before age 50

Study Design

Arms: Zolmitriptan 2.5 mg vs placebo

Patients per Arm: 219 zolmitriptan, 108 placebo

Outcome

• 2h headache response: 62% zolmitriptan vs 36% placebo (p<0.001)
• 4h pain-free: 38% zolmitriptan vs 13% placebo
• Nausea: 11% zolmitriptan vs 6% placebo; dizziness: 9% vs 3%

Bottom Line

Zolmitriptan 2.5 mg provided significantly greater headache relief and pain freedom at 2 and 4 hours compared to placebo, with a favorable safety profile.

Major Points

327 patients randomized 2:1 to zolmitriptan 2.5 mg or placebo for a single migraine attack
Headache response at 2 hours was significantly greater with zolmitriptan (62% vs 36%)
38% achieved pain freedom at 4 hours with zolmitriptan vs 13% with placebo
Adverse events were mild; most commonly nausea, dizziness, somnolence
No serious adverse events or significant ECG/lab abnormalities reported

Study Design

Study Type: Randomized, double-blind, placebo-controlled trial
Randomization: Yes
Blinding: Double-blind (participants, investigators, outcome assessors)
Sample Size: 327
Follow-up: 4 hours post-dose (single migraine attack)
Centers: 38
Countries: Multiple EU countries

Primary Outcome

Definition: Headache response at 2 hours (moderate/severe → mild/none)

Control	Intervention	HR/OR	P-value
36%	62%	-	<0.001

Limitations & Criticisms

Short follow-up (only single-attack, 4-hour evaluation)
Lack of active comparator (e.g., other triptans)
Majority of participants were women, limiting generalizability
Excludes patients with frequent or chronic migraine

Citation

Neurology. 1997;49(5):1210–1214. doi:10.1212/WNL.49.5.1210

View Original Publication →

Zolmitriptan 042 Trial

A randomized, double-blind, placebo-controlled trial of zolmitriptan 2.5 mg for the acute treatment of migraine

Clinical Question

Bottom Line

Major Points

Design

Inclusion Criteria

Exclusion Criteria

Baseline Characteristics

Arms

Outcomes

Subgroup Analysis

Criticisms

Funding

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