Evidence Table 4

Triptan compared with placebo: Characteristics and outcomes

Results
Author
Year
Country
Trial Name
(Quality Score)
Study designEligibility criteriaInterventionsAllowed other medications/interventionsMethod of Outcome Assessment and Timing of AssessmentAge
Gender
Ethnicity
Other population characteristicsNumber screened/eligible/enrolledNumber withdrawn/lost to fu/analyzedRelief at various timesPain Free at various times (%patients)Presence of migraine-associated symptoms at 2 hoursOther efficacy outcomesMethod of adverse effects assessmentAdverse Effects ReportedComments
Brandes
2005
USA & Canada
RCT, DB, ParallelIHS criteria of migraine with or without aura; aged 18–65 years; migraine history ≥1year; 1–4 attacks/month in preceding 3 monthsEletriptan (ele) 20 and 40mg

Placebo (pla)
Rescue medication permitted after 2 hours of no response (rescue medication could not be another dose of ele, another triptan, ergotamine, or ergotamine-like substance) Recurrences of headaches, after 2 hours response, were allowed a 2nd dose of study medicationPrimary efficacy endpoint: proportion of patients pain free at 2 hours postdose. Secondary efficacy endpoint: proportion of patients pain free at other assessment points (30 minutes, 1 hour, 1.5 hours, 4 hours and 24 hours); relief of associated symptoms (e.g. nausea, vomitting, photophobia, and phonophobia); use of rescure medication; sustained pain freeN=565
mean age:
ele 20mg=39.1
ele 40mg=38.7
pla=39.1
% female:
ele 20mg=79
ele 40mg=83
pla=85
ethnicity=nr
mean duration of illness:
ele 20mg=13.4 years
ele 40mg=14.0 years
pla=13.6 years
proportion without aura:
ele 20mg=73%
ele 40mg=68%
pla=67%
mean monthly attack
frequency:
ele 20mg=8.3
ele 40mg=8.6
pla=8.0
799/613/565nr/nr/565nrPain-free at 2 Hours:
ele 20mg=35% (p<0.01);
ele 40mg=47% (p<0.0001) vs.
pla=22%
ele 20mg vs pla absent the following symptoms:
nausea (83% vs 75%, p<0.05)
photophobia (66%vs 51%,
p<0.001)
phonophobia (74% vs 55%,
p<0.0001)

ele 40mg vs pla absent the following symptoms:
nausea (76% vs 75%, ns)
photophobia (74% vs 51%,
p<0.001)
phonophobia (81% vs 55%,
p<0.0001)
Migraine Free' outcome (complete relief at 2 hours, with no associated symptoms, and
normal functioning):
ele 20mg=32% (p<0.01);
ele 40mg=43% (p<0.0001) vs
pla=20%

Use of rescue medication:
ele 20mg=22% (p<0.01);
ele 40mg=18% (p<0.01) vs
pla=44%
Patient reportEle 20mg; Ele 40mg; Pla

Vomiting: 4.7%; 3.8%; 3.8%
Dizziness: 2.6%; 1.4%; 1.9%
Asthenia: 2.1%; 1.9%; 0.5%
Incidence of any adverse event: 28%;
23%; 32%
Cady
2006
USA
RCT, DB, parallel
Multicenter
IHS criteria for migraine with or without aura, aged 18 years or older, ≥6 months history of migraines, 1 to 4 migraine attacks/month, mild at onsent attacksRizatriptan (R) 10mg

Placebo (Pla)
Rescue medication was permittedPrimary effiacy outcome: pain freedome at 2 hours Secondary efficacy outcomes: 24-hour sustained pain freedom, pain freedom at 30, 45, 60, and 90 minutes, time to pain freedom up to 2 hours, presence of associated symptoms at 30, 45, 60, 90, and 120 minutes, use of rescue medication, presence of functional disability at 30, 45, 60, 90, and 120 minutesStudy 1
Mean age
(years): R10: 43;
Pla: 43
% Female: R10:
88.1; Pla: 89.3
% White: R10:
83.8; Pla: 80.2

Study 2
Mean age
(years): R10: 41;
Pla: 41
% Female: R10:
56.4; Pla: 91.1
% White: R10:
80.1; Pla: 77.5
Baseline associted symptoms
Study 1
Photophobia: R10: 66.9%; Pla:
65.%
Phonophobia: R10: 54.%; Pla:
48.6%
Nausea: R10: 31.7%; Pla:
29.4%
Vomiting: R10: 0.8%; Pla: 0.6%

Study 2
Photophobia: R10: 60.4%; Pla:
50.9%
Phonophobia: R10: 43.8%; Pla:
44.4%
Nausea: R10: 35.6%; Pla:
37.9%
Vomiting: R10: 1.5%; Pla: 1.8%
Study 1
598/589/583

Study 2
577/570/564
Study 1
31/6/351

Study 2
41/4/331
NRPain Freedom at 2 Hours
Study 1
R10: 57% vs Pla: 31% (p<0.001)
Study 2
R10: 59% vs Pla: 31% (p<0.001)
Sustained Pain Freedom at 24 Hours
Study 1
R10: 43% vs Pla: 23% (p<0.001)
Study 2
R10: 48% vs Pla: 25% (p<0.001)
Photophobia
Study 1
R10: 23% vs Pla: 44% (p<0.05)
Study 2
R10: 25% vs Pla: 40% (p<0.05)
Phonophobia
Study 1
R10: 18% vs Pla: 35% (p<0.05)
Study 2
R10: 21% vs Pla: 34% (p<0.05)
Nausea
Study 1
R10: 16% vs Pla: 19% (NS)
Study 2
R10: 15% vs Pla: 30% (p<0.05)
Vomiting
Study 1
R10: 2% vs Pla: 2% (NS)
Study 2
R10: 2% vs Pla: 2% (NS)
Need for Rescue Medication at 2 Hours
Study 1
R10: 35% vs Pla: 54% (p<0.05)
Study 2
R10: 34% vs Pla: 53% (p<0.05)

Functional Disability at 2 Hours
Study 1
R10: 31% vs Pla: 54% (p<0.05)
Study 2
R10: 34% vs Pla: 56% (p<0.05)
Patient reportIncidence of adverse effects
Study 1
R10: 21% vs Pla: 12.4%
Study 2
R10: 21.8% vs Pla: 9.5%
Dry mouth
Study 1
R10: 2.8% vs Pla: 1.7%
Study 2
R10: 2.4% vs Pla: 2.4%
Paresthesia
Study 1
R10: 2.3% vs Pla: 0%
Study 2
R10: 2.1% vs Pla: 0.6%
Dizziness
Study 1
R10: 5.9% vs Pla: 2.3%
Study 2
R10: 3.3% vs Pla: 2.4%
Somnolence
Study 1
R10: 3.1% vs Pla: 1.7%
Study 2
R10: 3.3% vs Pla: 1.8%
Fatigue
Study 1
NR
Study 2
R10: 3.3% vs Pla: 1.2%
Carpay
2004
Europe

Fair quality
RCT
DB
Parallel group
Single attack
Between 18 and 65 years of age; at least 1-year history of migraine (IHS criteria) with or without aura; 1–6 attacks/month in preceding 2 months; history of moderate to severe migraines typically preceded by a mild-pain phase. Patients were eligible for the study regardless of previous experience with triptan therapy.Sumatriptan rapid release (SRR) formulation 50 mg and 100 mg
Placebo
Acute migraine medication (excluding an ergo-containing medication or a triptan) allowed from 2 through 24 hours after dosing for patients who were not pain free at 2 hours or who had a return of moderate or severe pain and did not wish to take a second dose of study medicationPrimary efficacy endpoint=proportion of patients who were pain free 2 hours after dosing

Severity rated using 4-point scale (0=none; 1=mild; 2=moderate; 3=severe) recorded on a diary card before dosing and 30 minutes, 45 minutes, 1 hour and 2 hours after dosing
n=481
mean age=40.6
82.9% female
99% white
Without aura only=78.7%
With aura only=8.3%
With and without aura=13%
Using triptans at study entry=75%
Used triptans in past year=4.6%
Used triptans sometime in past=6.2%
Never used triptans=14.1%
Severity at onset
Mild=93.5%
Moderate=5.3%
Severe=1.1%
nr/nr/481 randomized/432 treated a migraine attack and provided = 1 postdose efficacy assessment37(8.6%) withdrawn/9(2.1%) lost to fu/432 analyzednrSRR100 vs SRR50 vs placebo
30 minutes: 10.6* vs 3.6 vs 1.9
45 minutes: 24.6§ vs 18.2 vs 9.1
1-hour: 44.4§ vs 36.5* vs 18.9
2-hours: 66.2§ vs 51.1§ vs 19.6

Sustained (2–24 hours) pain-free:
32.1* vs 40.1* vs 9.8
SRR50 vs SRR100 vs placebo

Nausea: 15.6* vs 22.3* vs 38.4
Photophobia: 25.4* vs 23.6* vs 48.7
Phonophobia: 23.1* vs 20.4* vs 43
SRR50vs SRR100 vs placebo

Migraine-free (pain-free AND no associated symptoms)
30 minutes: 3.7 vs 7.1* vs 2
45 minutes: 14.7 vs 16.4* vs 7.3
1 hour: 30.1* vs 31.4* vs 17.2
2 hours: 44.9* vs 50.7* vs 17.1
Tolerability was assessed by calculating the incidence of specific adverse events, defined as any untoward medical occurrences, regardless of suspected cause, that were reported by a patient or noted by a clinician during the studySRR50 vs SRR100 vs placebo (% patients)

Overall drug-related adverse events:
10.2% vs 16.9* vs 5.2
Nausea and vomiting: <1 vs 5 vs 2
Chest symptoms: 2 vs 3 vs 0
Malaise and fatigue: 1 vs 3 vs <1
Diener
2005
Germany

Diener
2005
Germany (companion paper)
RCT, DB, ParallelIHS criteria for migraine with or without aura for ≥1 year, had experienced unsatisfactory response to sumatriptan on ≥2 occassions, experienced ≥1 moderate or severe migraine attack in each of the 2 months proceding the studyAlmotriptan 12.5mg (Alm)

Placebo (Pla)
Rescue medication, choosen by the investigator, was permittedPrimary efficacy outcome: pain relief at 2 hours Secondary efficacy outcome: pain-free at 2 hours, sustained pain-free, use of rescue medication within 24 hoursMean age (years)
Alm: 41.1; Pla:
41.4
% Female
Alm: 88; Pla:
85.8
% White
Alm: 99.4; Pla:
99.1
Mean Height (cm)
Alm: 167.6; Pla: 168.1
Mean Weight (kg)
Alm: 70.6; Pla: 70.47
Headache severity
Severe: Alm: 69.7% Pla: 71.7%
Moderate: Alm: 30.3% Pla:
28.3%
328/245/22123/NR/198Pain-reilef at 2 Hours
Alm: 47.5% vs Pla: 23.2% (p<0.001)
Pain-free at 2 Hours
Alm: 33.3% vs Pla: 14.1%
(p<0.005)
Sustained pain-free
Alm: 20.9% vs Pla: 9% (p<0.05)
NRUse of rescue medication
Alm: 26.6% vs Pla: 46.9%
(p<0.005)
Patient reportTreatment-emergent adverse events
Alm: 7.1% vs Pla: 5.1% (p=0.77)
Eletripan Steering Committee
2002
Japan

Fair quality
Randomized controlled trial
Multicenter

Single dose
IHS criteria; 1 attack per 6-week periodEletriptan (ele) 20, 40 and 80 mg

Placebo (pla)
Rescue medication permitted nrPrimary efficacy endpoint: Proportion of patients who experienced headache response 2 hours post-dose. Patients recorded migraine severity in a diary at 0.5, 1, 2, 4, and 24 hours post-dose.n=402
avg age 35.5
74.1% female
100% Japanese
Without aura=48.6%
With aura=34.2%
With and without aura=17.1%
Baseline severity assessment:
No pain=0%
Mild pain=0%
Moderate pain=75.7%
Severe pain=22.4%
nr/nr/40276(18.9%) withdrawals/3(0.7%) lost to fu/321 analyzed for safety; 309 for primary endpoint; 307 for other efficacy endpointsAt .5 hour: nr
At 1 hour: nr
At 1.5 hours: nr
At 2 hours: ele=64%; 67%; 76% pla= 51%
At 2 hours: ele=24%; 22%; 28% pla=13%Vomiting:
ele=96%; 99%; 95%; pla=96%
Nausea:
ele=70%; 74%; 41: pla= 68%
Photophobia:
ele=84%; 83%; 86%; pla=71%
Symptom free at 2 hours:
ele=65%; 65%; 75%; pla=54%
24 hour sustained pain-free:
ele=21%; 18%; 26%; pla=9%
The incidence of adverse events was detected by indirect subject questioning, physical examination, and from laboratory safety data and entries in subject diaries.Total: ele=16.3%; 32.5%; 45.5%; pla=15.5%
Asthenia: ele=1.3%, 2.5%, 11.7%; pla=1.2%
Parasthesia: ele=0, 3.8%, 1.3%; pla=0
Somnolence: ele=6.3%, 10.0%, 16.9%; pla=3.6%
Freitag, 2008
(companion to Matew 2007)
RCT, DB, Multicenter, ParallelIHS criteria-migraine with or without aura of moderate pain intensity for ≥ 1 year, 2–6 headaches per month for last 6 monthsAlmotriptan 12.5mg (Alm)

Placebo (Pla)
Rescue medication permittedFunctional disability assessment using 4 categories measured at 0.5, 1, 2, 4 and 24 hours

MQoL questionnaire at 24 hours post treatment of each attack
40.4 yrs
87% female
White: 82.2%
Black: 12.1%
Asian: 2.5%
Hispanic : 2.9%
Other: 0.3%
Weight: lbs (SD): 167.4(37.7)
MiDAS Score (SD): 18.5(14.7)
Height:inches (SD): 65.4 (3.2)
Functional disability:
perform normal activity 12.3%, disturbed but could continue work:
77.1%, bed rest required: 10.1%
Migraine associated symptoms:
phonophobia: 73.7%, photophobia:
75.2%, nausea: 31.4%
NR/NR/378NR/NR/31524 hour QOL
social function domain p<0.05 (all 3 attacks), feelings/concern domain: p<0.05 for attack 1, p<0.01 for attack 2, p<0.001 for attack 3.

Three pretreatment variables 1) functional level (p=0.011), 2) pain intensity (p=0.0089), and 3) MIDAS (p=0.0152) correlated with return to normal function at 2hr. Correlation of other pretreatment variables photophobia, phonophobia, nausea and vomiting were NS.
% of patients pain free and performing normal activities for pooled group (Attack 1)
76.9% at 0.5 hr, 94.6% at 1 hr, 91.7% at 2 hrs
% of patients with mild pain and performing normal activities for pooled group (Attack 1)
27.5% at 0.5 hr, 34.0 at 1 hr, 44.8 at 2 hrs

Pain free (from graph)
A vs placebo
at 2 hrs: 38% vs 25% (p=0.0004)
at 4 hrs: 40% vs 22% (p<0.0001)
24 hrs: 43% vs 30% (p=0.0008)
% patients with normal function and no migraine assciated symptoms compared to patients with symptoms (data from graph) pooled group (p<0.0001 for each group)
No phonophobia: 72% normal, with phonophobia: 19% normal
No photophobia: 75% normal, with phonophobia: 20% normal
No Nausea: 56% normal, with nausea: 18% normal
A vs Pla
Functional disability at 2 hours:
normal funtion 54.4% vs 38.1%, disturbed function 32.5% vs 45.2%, bed rest 13.1% vs 16.1%, ER hospitalization 0 vs 0.6% (p=0.007)
at 4 hours:
normal funtion 74.5% vs 54.3%, disturbed function 20.1% vs 29.3%, bed rest 4.7% vs 15.7%, ER hospitalization 0.7% vs 0.7% (p<0.001)
Return to normal function at 2, 4, 24 hours post treatment for pretreatment impairment group (N=276):
2 hrs: 51.1% vs 34.1% (p=0.011)
4 hrs: 64.% vs 39.4% (p<0.001)
24 hrs: 60.8% vs 47.6% (p=0.038)
Normal function for whole group
at 2 hours: 48.7% vs 36.5%, at 4 hours: 68.6 vs 53.7% at 24 hrs: 83.5% vs 80.4%
Normal functioning p<0.0026 and <0.0007 at 2 and 4 hours (favoring Alm) for Attack 1, p=0.0003 and p=0.0112 at 1 and 4 hrs and p=0.0448 for Attack 2 at 2 hrs (p values vs placebo)
Patient reportA vs Pla:
% patients reporting AE: 23% vs 23.7%
treatment emergent AE with a frequency of ≥1%: 9.8% vs 6.4%
Somnolence:1.1% vs 2.3%
Nausea: 1.1% vs 1.7%
Vomiting: 1.1% vs 0.6%
Fatigue: 1.1% vs 0%
Goadsby
2008
Multinational
RCT, DB, Multicenter, ParallelIHS criteria-with or without aura for at least 1 yrMigraine attacks of atleast moderate pain intensity within the lpat year. Avg frequency of 2–6 episodes per month during the last 3 months. History of untreated or unsuccessfully treated migraine headaces > 4 hours durationAlmotriptan 12.5mg (Alm)

Placebo (Pla)
Rescue medication permittedPrimary efficacy endpoint: % of pain-free patients 2 hours, comparison between those treated early with mild pain vs moderate or severe baseline pain.
Secondary endpoints: % of patients pain free at 0.25, 0.5, 1, 1.5 and 24 h post dose in the moderate-severe baseline pain arms Sustained pain-free response at 24 h, pain-free at 2 hours without return of headache and not using rescue medication in the following 24 h, % of patients taking rescue medication % patients with relapse in 24 hours and 24 and 48 hours post dose Total attack duration in hours and time lost to attack in hours Treatment satisfaction rate using VAS migraine-associated symptoms at baseline and 2 hours post treatment presence of cutaneous allodynia by questionnaire at baseline or 2 h post treatment
38.26 yrs
84.2% female
Asian: 0.2%
Black: 0.5%
Caucasian: 98.3%
Other: 1.0%
BMI (kg/m2)
Mean (SD)
23.60(3.98)
491/NR/49187/NR/404NR1) A 12.5 (mild) 2) A 12.5 (moderate to severe)
3) Pla (mild) 4) Pla (moderate to severe)
Pain free at 2 hrs: 49% vs 40% vs 25% vs 15%
Differences: 1 vs. 2 NS (p=0.2154), 1 vs. 3 and 2 vs. 4 both significant (p < 0.001)

Sustained pain-free (2–24 hrs) 46% vs 30% vs 16% vs 11%
Differences: 1 vs. 2 significant
(p=0.024), 2 vs. 4 significant
(p=0.0018), 1 vs. 3 significant
(p<0.0001), 3 vs. 4 NS (p=0.38)

Pain-free data at 2 hours in AwM group
Pain free at 2 hrs: 54% vs 38% vs 25% vs 18%
Differences: 1 vs. 2 significant
(p=0.02)
Therapeutic gain at 2 hours:
A mild vs A moderate to severe vs
placebo mild vs placebo moderate to
severe:
Nausea
1.8 vs 28.9 vs 9.2 vs 9.6
Vomiting
-8.0 vs -1.7 vs −0.4 vs 3.1
Photophobia
17.0 vs 30.3 vs 12.5 vs 12.8
Phonophobia
17.7 vs 24.7 vs 8.5 vs 9.8
Osmophobia
6.4 vs 8.7 vs 0.4 vs 4.4
1) A 12.5 (mild) 2) A 12.5 (moderate to severe) 3) Pla (mild) 4) Pla (moderate to severe)
Median duration of migraine attack from onset to resolution of pain
(AwM based data):
1) 2hrs 2) 5hrs, 1 significantly shorter vs. 2 (p=0.0005)
Median duration of migraine attack from time of dosing to resolution of pain (AwM based data):
1) 1.6 hr 2) 1.9 hr, 1 vs 2 NS.
Median time lost in daily activities
1) 0 hr, 2) 2hr, 3) 2hr and 4) 2 hr.
3 vs. 4 difference NS, 1 vs 2 difference significant (p=0.0015)
Headache recurrence within 24 hrs
6% vs. 24 % vs. 37% vs. 27%
1 vs. 2 significant difference
(p=0.0124), 3 vs. 4 difference NS.
Use of rescue medication
1 vs. 2 Difference NS p=0.1921
1 vs. 3, more in 3 took rescue med, p<0.0001
2 vs. 4, more in 4 took rescue med, p<0.0001 3 vs. 4, difference NS.
Patient report4.9% of subjects had 8 AE in the A mild group
4% of subjects had 4 AE in A moderate and severe group
4.7% of subjects had 5 AE in placebo mild group
4% of subjects had 5 AE placebo moderate to severe group
Goldstein
2005
USA
RCT, DB, Parallel
Multicenter
IHS criteria for migraine with or without aura; report 1 to 8 migraines/month; migraines are of at least moderate intensity; be able to distinguish migraines from other headachesSumatriptan succinate (sum) 50mg

Acetaminophen 500mg, aspirin 500mg, caffeine 130mg (AAC)

Placebo (pla)
Rescue medication permittedEfficacy variables recorded at baseline, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, and 4 hours postdose:
- headache pain intensity
- headache pain relief
- functional disability
- associated gastrointestinal and neurologic symptoms Efficacy variables without a fixed time point:
- onset of meaningful migraine relief
- subject global evalutation of study medication effectiveness
- investigator global evalutation of study medication effectiveness
- rescue medication usage
Mean age (years): 38.1
82% Female
NR188/171/1700/0/170Pain-relief (scale 0–4, with 0=no relief and 4=complete relief)
At 2 Hours:
AAC: 2.5 vs sum: 1.9 (p<0.05) vs pla: 1.6
At 3 Hours:
ACC: 2.9 vs sum: 2.2 (p<0.05) vs pla: 1.8
At 4 Hours:
ACC: 2.9 vs sum: 2.3 (p<0.05) vs pla: 1.8
NRACC group had significantly more decrease of phonophobia (p≤0.044) and photophobia (p≤0.015) than sum group
No difference found for vomiting or nausea
Headache Response (baseline of moderate/severe pain reduced to mild/none):
At 2 Hours:
ACC: 84% vs sum: 65%
(p≤0.027) vs pla: 52%
At 3 Hours:
ACC: 94% vs sum: 70%
(p<0.02) vs pla: 56%
At 4 Hours:
ACC: 98% vs sum: 72%
(p<0.02) vs pla: 56%
Patient reportChest tightness: sum group=1 subject

Gastrointestinal complaints:
AAC: 15 (21/7%) vs sum: 5 (7.5%) vs pla: 2 (5.7%)
Jelinski
2006
Canada
RCT, DB, Double-dummy, placebo controlled, parallel MulticenterIHS criteria for migraine with or without aura; aged 18 to 65 years, 1 to 6 migraines/month, moderate/severe migraine painSumatriptan 50mg (S50) and 100mg (S100)

Placebo (Pla)
NRPrimary efficacy outcome: proportion of patients pain-free at 1, 2, 4 and 24 hoursPla; S50; S100
Mean age
(years): 40.7; 39.8; 39.8
% Female: 83; 87; 86
% White: 92; 95; 96
Pla; S50; S100
Migraine History
%without aura: 67; 63; 71
% with aura: 10; 10; 7
429/364/361NR/NR/361NRPain-Free at 1 Hour
S50: 24% Pla: 7% (p<0.001)
S100: 24% vs Pla: 7% (p<0.001)
Pain-Free at 2 Hours
S50: 40% vs Pla: 16% (p<0.001)
S100: 50% vs Pla: 16% (p<0.001)
Pain-Free at 4 Hours
S50: 50% vs Pla: 17% (p<0.001)
S100: 56% vs Pla: 17% (p<0.001)
Pain-Free at 24 Hours
S50: 37% vs Pla: 15% (p<0.001)
S100: 45% vs Pla: 15% (p<0.001)
Nausea reported at 2 Hours:
S50: 26% vs S100: 26% vs Pla:
38%
NRPatient reportS100: paraesthesias, chest symptoms, and throat contstriction reported by 3% of subjects
Mathew
2007
USA
RCT, DB, Parallel
Multicenter
IHS criteria for migraine with or without aura, aged 18 to 65 years, 2 to 6 migraines/month, moderate/severe migraine pain, differentiate migraines from other headaches,Almotriptan 12.5mg (Alm)

Placebo (Pla)
Rescue medication was permittedPrimary efficacy outcome: proportion of patients pain-free at 2 hours
Secondary efficacy outcomes (in proportions): pain-free at 0.5, 1, 4, and 24 hours; pain-relief at 0.5, 1, 2, 4, and 24 hours; modified pain-relief at 0.5,1, 2, 4, and 24 hours; sustained pain-free; use of rescue medication; level of migraine-associated symptoms at baseline at 0.5, 1, 2, 4, and 24 hours; and level of functional disability at 1, 2, 4, and 24 hours
Mean age
(years): 40.4
86.8% Female
82% White
Mean weight (lbs): 167.8
Mean heaght (inches): 65.5
NR/NR/37861/NR/317Pain-relief at 1 Hour (%)
Alm: 54.3 vs Pla: 41.1 (p=0.019)

Pain-relief at 2 Hours (%)
Alm: 72.3 vs Pla: 48.4 (p<0.001)

Pain-relief at 4 Hours (%)
Alm: 74.5 vs Pla: 47.4 (p<0.001)

Pain-relief at 24 Hours (%)
Alm: 73.4 vs Pla: 48.4 (p<0.001)
Pain-free at 1 Hour
Alm: 16.7 vs Pla: 8.4 (p=0.026)

Pain-free at 2 Hours
Alm: 37 vs Pla:23.9 (p=0.01)

Pain-free at 4 Hours
Alm: 42 vs Pla: 21.9 (p<0.001)

Pain-free at 24 Hours
Alm: 38.9 vs Pla: 27.1 (p=0.031)
Phonophobia
At 2 to 4 hours and 4 to 24 hours after treatment, Alm group was significantly lower than Pla group (p=0.002, p<0.001, respectively)

Photophobia
At 2 to 4 hours and 4 to 24 hours after treatment, Alm group was significantly lower than Pla group (p<0.001 for both time periods)

Nausea
At 4 to 24 hours after treatment, Alm group was significantly lower than Pla group (p=0.014)
Functionality
Of those reporting functional disability at time of treatment, proportion reporting normal functioning at 2 Hours:
Alm: 54.4 vs Pla: 38.1 (p=0.007)
At 4 Hours:
Alm: 74.5 vs Pla: 54.3 (p<0.001)
Patient reportSomnolence
Alm: 1.1% vs Pla: 2.3%
Nausea
Alm: 1.1% vs Pla: 1.7%
Vomiting
Alm: 1.1% vs Pla: 0.6%
Fatigue
Alm: 1.1% vs Pla 0%
Sakai
2002
Japan

Fair quality
Randomized controlled trial
Multicenter

Single dose
IHS criteria of migraine with or without aura; age of migraine onset <50 years; migraine history ≥1 year; 1–6 attacks/month in preceding 3 monthsZolmitriptan (zol) 1, 2.5, 5 mg
Placebo (pla)
Type(s) of rescue medication approved 4-hours post-dose nrPrimary efficacy endpoint: proportion of patients with headache response at 2h post dose. Patients recorded migraine intensity on diary cards at 0.5, 1, 2, and 4h post-dose.n=289
avg age 38.3
74.2% female
100% Japanese
Without aura=64%
Associated symptoms:
Nausea=90%
Vomiting=54%
Photophobia=56%
Phonophobia=45%
Severity:
Moderate=73%
nr/nr/28958/289(20%) did not take medication; a further 29/287(10%) were excluded from efficacy analysis due to protocol deviations/lost to fu nr/202 analyzedAt .5 hour: zol=8.5%; 9.8%; 13.7%
pla= 12.2%
At 1 hour: zol=30.4%; 28.3%; 32.7%
pla=26.5%
At 1.5 hours: nr
At 2 hours: zol=53.3%; 55.6%; 65.4%
pla=37.5%
At 2 hours: zol=17.8%; 18.5%; 23.1%
pla=14.6%
Vomiting:
zol=95.6%; 98.1%; 98%; pla=95.8%
Nausea:
ele=53.3%; 61.1%; 64.7: pla= 54.2%
Photophobia:
ele=82.2%; 83.3%; 78.4%;
pla=77.1%
Symptom free at 2 hours:
nr
24 hour sustained pain-free:
Complete response (headache response at 2h and then no recurrence or use of escape medication within 24h)
zol=37.8%, 46.3%, 46.2%
pla=22.9%
The assessment of tolerability was based on the reporting of adverse events in patient diaries.Asthenia: zol=1.9%, 1.6%, 7.0%; pla=1.7%
Parathesia: zol=0, 0, 5.3%; pla=0
Somnolence: zol=0, 3.3%, 5.3%; pla=1.7%
Sheftell 2005
USA
RCT, DB, Parallel, 2 studiesaged between 18–65 years, ≥ 6 month history f migraine with/without aura, 1–6 migraines per month during the 3 months before screening, previous thistory of tripatn therapy was not an exclusion criteriaFast-disintegrating, rapid release sumatriptan 50 mg:
N=902
Fast-disintegrating, rapid release sumatriptan 100 mg:
N=902
Placebo: 892
Recurrence of headache were allowed a second dose of study medication, patients with no relief after 2 hours weer allowed an nonprohibited acute migraine medicationPrimary efficacy endpoint was time to onset of pain relief. Responses recorded every 2 hours between after dosing for 24 hour periods. Patients rated pain relief and recurrence.Studies
combined: N= 2696
Mean age: 40 years
Female: 85%
White: 92%
History of triptan use:
Study 1: S50: 77% vs S100:
79% vs placebo: 78%
Study 2: S50: 84% vs S100:
84% vs placebo: 84%

History of migraine without aura only:
Study 1: S50: 72% vs S100:
68% vs placebo: 71%
Study 2: S50: 65% vs S100:
70% vs placebo: 67%
NR/NR/333173/NR/2696Pain-relief at 2 Hours:
S50: 67% vs S100: 72% vs placebo: 42%;
p< 0.05 for both doses vs placebo
Pain-free at 2 Hours:
S50: 40% vs S100: 47% vs
placebo: 15%; p≤ 0.001
NRNRPatient reportAny drug-related adverse event:
Study 1: S50: 8% vs S100: 12% vs
placebo: 3%
Study 2: S50: 12% vs S100: 19% vs
placebo: 5%

Nausea (drug-related):
Study 1: S50: <1% vs S100: <1% vs
placebo: 0
Study 2: S50: 1% vs S100: 3% vs
placebo: 1%

Paresthesia (drug-related):
Study 1: S50: <1% vs S100: <1% vs
placebo: 0
Study 2: S50: 1% vs S100: 3% vs
placebo: <1%
Silberstein
2008
US
RCT, DB, ParallelMen and women aged 18 to 65 years with ≥6 month history of migraine with or without aura as defined by the ICHD-2, and had experienced 2–6 migraine attacks per month in last 3 months.Sumatriptan 85/mg/day + naproxen sodium 500mg/day (Sum)

Placebo (Pla)
Rescue medications were allowedPatients rated pain severity (0=none, 3=severe) in diariesMean age (years): 40.4
88.7% Female
86.5% White
Mean attacks per month: 3.8
Mean age of onset: 22.4 years
Previous triptan use: 66.2%
NR/1305/112211/NR/1111NRStudy 1
Pain free at 30 min
Sum: 5% vs Pla: 2% ( p=0.016)
Pain free at 1 hr
Sum: 20% vs Pla: 7% (p<0.001)
Pain free at 2 hr
Sum: 52% vs Pla: 17% (p<0.001)
Pain free at 4 hr
Sum: 70% vs Pla: 25% (p<0.001)
Pain free 2–24 hr
Sum: 45% vs 12% (p<0.001)
Study 2
Pain free at 30 min
Sum: 6% vs Pla: 2% ( p=0.021)
Pain free at 1 hr
Sum: 24% vs Pla: 7% (p<0.001)
Pain free at 2 hr
Sum: 51% vs Pla: 15% (p<0.001)
Pain free at 4 hr
Sum: 67% vs Pla: 25% (p<0.001)
Pain free 2–24 hr
Sum: 40% vs Pla: 14% (p<0.001)
Nausea
Study 1: Sum: 17% vs Pla: 24% (p=0.018)
Study 2: Sum: 19% vs 31% (p<0.001)
Photophobia
Study 1: Sum: 31% vs Pla: 57% (p<0.001)
Study 2: Sum: 22% vs Pla: 55% (p<0.001)
Phonophobia
Study 1: Sum: 26% vs Pla: 54% (p<0.001)
Study 2: Sum: 20% vs Pla: 46% (p<0.001)
Neck pain/discomfort
Study 1: Sum: %35 vs Pla: 44% (p=0.001)
Study 2: Sum: 28% vs 54% (p<0.001)
Sinus pain/pressure
Study 1: Sum: 19% vs Pla: 33% (p<0.001)
Study 2: Sum: 23% vs 38% (p<0.001)
NRPatient reportIncidence of AEs reported
Study 1: Sum: 11% vs Pla: 7%
Study 2: Sum: 14% vs 9%
2 studies reported in one publication. Same methods for both studies.
Sumatriptan Rapid Release formulation
Tepper
2006
USA
RCT, DB, Parallel
Multicenter
IHS criteria for migraine without aura, aged 18 to 65 years, met either headache pain criteria or associated symptom criteria, triptan- and ergot-naïveSumatriptan (S) 25, 50, or 100mg

Placebo (Pla)
Rescue medication was permittedPrimary efficacy outcome: % with headache relief at 2 hours
Secondary efficacy outcomes: % with headache relief at 0.5, 1, 1.5, and 4 hours, % pain free at 0.5, 1, 1.5, 2, and 4 hours; % with nausea, photophobia and phonophobia at 0.5, 1, 1.5, 2, and 4 hours
Pla; S25; S50; S100
Mean age
(years): 37.8; 37.9; 39.1; 39.3
% Female: 80; 68; 74; 73
% White: 73; 71; 71; 75
Previous headache treatment with OTC analgesics (%):
Pla: 93
S25: 93
S50: 95
S100: 94
NR/NR/67774/22/581Headache relief at 2 Hours (%)
S25: 57 vs S50: 53 vs S100: 59 vs Pla:
47% (p=0.053 for S100 vs Pla)
Headache relief at 4 Hours (%)
S25: 49 vs S50: 57 vs S100: 64 vs Pla: 40
(p<0.01 for S50 vs Pla and S100 vs Pla)
Pain-free at 2 Hours
S25: 31 vs S50: 28 vs S100: 32 vs
Pla: 25 (NS)
Pain-free at 4 Hours
S25: 39 vs S50: 41 vs S100: 49 vs
Pla: 26 (p≤0.023 for all comparisons)
Nausea
Baseline: 14% to 20% of each group
2 Hours: 20% to 50% of baseline reporters still had nausea

Photophobia
Baseline: 41% to 47% of each group
2 Hours: 50% of baseline reporters still had photophobia

Phonophobia
Baesline: 34% to 46% of each group
2 Hours: 50% of baseline reporters still had phonophobia
Pla group took 2nd dose or rescue medication significantly earlier compared with S100 group (p=0.002)Patient reportIncidence of adverse events
Pla: 4%; S25: 11%; S50: 14%; S100:
17%

Nausea
Pla: 0%; S25: 4%; S50: 5%; S100: 6%

Dizziness
Pla: 0%; S25: <1%; S50: 3%; S100: 2%

Vomiting
Pla: <1%; S25: 0%; S50: <1%; S100: 3%
Tfelt-Hansen
2006
Denmark
RCT, DB, ParallelPatients between 18 and 65 years suffering from migraines with or without aura as defined by the 1988 IHS criteria for ≥ 1 year and had a history of 6–12 migraine attacks/year, those who had the experience that the headache became moderate or severe following a mild phase, were able to differentiate migraine from other headaches and had not treated a migraine with a triptan within the last 6 months.Sumatriptan 50mg (Sum)

Placebo (Pla)
Rescue medication was permittedPrimary efficacy endpoint: % pain free after 2 hours

Patients recorded their pain severity and symptoms at 30 minutes, 1 hour, 2 hours, and 24 hours after taking study medication
Mean age
(years): Sum: 40
(males) & 36
(females); Pla:
48 (males) & 36
(females)
78.2% females
Ethnicity: NR
Migraine with aura: 10.9%
Migraine without aura: 80.2%
Migraine with and without aura: 8.9%
Previous triptan use: 11.9%
Concurrent medications: 66.3%
158/150/1012/NR/99NRPain free at 2 hours
Sum: 39% vs Pla: 18%
Sustained pain free response
Sum: 33% vs Pla: 13%
Stated no difference between groups, but data not presentedNRPatient reportPatients with AEs
Sum: 51% vs Pla: 15%
Most common AEs
Nausea (N=5)
Paraesthesia (N=4
Fatigue (N=3)
Chest pressure sensation (N=2)
Wendt
2006
USA
RCT, DB
Multicenter
IHS criteria for migraine with or without aura, aged 18 to 60 years, presented with acute migrain attack with moderate or severe painSumatriptan (S) 4mg Inj

Placebo (Pla)
Rescue medication was permittedPrimary efficacy outcomes: migraine symptoms and severity of headache pain just prior to treatment administration, then at 10, 20, 30, 40, 50, 60, 90, and 120 minutes after dosingMean age
(years): S4: 38.3; Pla: 38.1
% Female: S4:
86; Pla: 88
% White: S4: 95; Pla: 91
Migraine with aura: S4: 8%; Pla: 8%
Migraine without aura: S4:
65%; Pla: 68%
Migraine with or without aura:
S4: 27%; Pla: 24%
Use of migraine prophylaxis
(%): S4: 56; Pla: 66
Severity of pain(%)
Mild: S4: <1%; Pla: 1%
Moderate: S4: 47%; Pla: 51%
Severe: S4: 53%; Pla: 48%
NR/NR/577NR/NR/577Pain-relief at 10 minutes (%)
S4: 11% vs Pla: 6% (p=0.039)
Pain-relief at 20 minutes (%)
S4: 27% vs Pla: 11% (p<0.001)
Pain-relief at 30 minutes (%)
S4: 43% vs 18% (p<0.001)
Pain-relief at 40 minutes (%)
S4: 56% vs Pla: 23% (p<0.001)
Pain-relief at 50 minutes (%)
S4: 62% vs Pla: 24% (p<0.001)
Pain-relief at 1 hour (%)
S4: 67% vs Pla: 25% (p<0.001)
Pain-relief at 90 minutes (%)
S4: 69% vs Pla: 26% (p<0.001)
Pain-relief at 2 hours (%)
S4: 70% vs Pla: 22% (p<0.001)
Pain-free at 10 minutes
S4: 1% vs Pla: 1% (NS)
Pain-free at 20 minutes
S4: 5% vs Pla: 2% (NS)
Pain-free at 30 minutes
S4: 10% vs 3% (p<0.001)
Pain-free at 40 minutes
S4: 18% vs Pla: 4% (p<0.001)
Pain-free at 50 minutes
S4: 26% vs Pla: 6% (p<0.001)
Pain-free at 1 hour
S4: 34% vs Pla: 7% (p<0.001)
Pain-free at 90 minutes
S4: 43% vs Pla: 9% (p<0.001)
Pain-free at 2 hours
S4: 50% vs Pla: 11% (p<0.001)
Nausea
30 minutes: S4: 39% vs Pla: 49%
(p=0.021)
2 hours: S4: 12% vs Pla: 37%
(p<0.001)
Photophobia
10 minutes: S4: 80% vs Pla: 87%
(P=0.046)
2 hours: S4: 27% vs Pla: 56%
(p<0.001)
Use of rescue medication S4: 22% vs Pla: 45%Patient report and lab testsIncidence of adverse events
S4: 69% vs Pla: 39% (p<0.001)
Injection site reaction
S4: 43% vs Pla: 15%
Tingling
S4: 12% vs Pla: 3%
Dizziness or vertigo
S4: 10% vs Pla: 5%
Warm or hot sensation
S4: 8% vs Pla: 2%
Nausea, vomiting, or both
S4: 7% vs Pla: 8%
Winner
2006
USA
RCT, DB, Parallel
Multicenter

2 studies
IHS criteria for migraine with or without aura, aged 18 to 65 years, 1 to 6 migraines/month, awakened with moderate to severe migraine pain ≥1 in last 3 monthsSumatriptan succinate (S)
6mg Inj

Placebo (pla)
Rescue medication was permittedPrimary efficacy endpoints: % pain-free at 2 hours; % migraine free at 2 hours; % at normal functioning level at 2 hours; % using rescue medicationStudy 1
Mean age
(years): S6: 40.2;
Pla: 41.4
S6: 84% Female;
Pla: 82% Female
S6: 83% White;
Pla: 78% White
Study 2
Mean age
(years): S6: 38.8;
Pla: 39.3
S6: 93% Female;
Pla: 81% Female
S6:81% White;
Pla: 89% White
Migraines without aura
Study 1: S6: 59%; Pla: 62%
Study 2: S6: 76%; Pla: 71%
Migraines with aura
Study 1: S6: 17%; Pla: 18%
Study 2: S6: 14%; Pla: 12%
Migrains with or without aura
Study 1: S6: 24%; Pla: 20%
Study 2: S6: 11%; Pla: 17%
Study 1
NR/NR/357
Study 2
NR/NR/351
Study 1
1/NR/297
Study 2
1/NR/287
NRAt 2 Hours
Study 1: S6: 48% vs Pla: 18%
(p<0.001)
Study 2: S6: 57% vs Pla: 19%
(p<0.001)
Sustained pain-free
Study 1: S6: 32% vs Pla: 14%
(p<0.001)
Study 2: S6: 34% vs Pla: 15%
(p<0.001)
% with symptoms
Nausea
Study 1: S6: 20% vs Pla: 38%
(p<0.001)
Study 2: S6: 17% vs Pla: 39%
(p<0.001)
Vomiting
Study 1: S6: 1% vs Pla: 7% (NS)
Study 2: S6: 1% vs Pla: 5% (NS)
Photophobia
Study 1: S6: 30% vs Pla: 50%
(p<0.001)
Study 2: S6: 27% vs Pla: 62%
(p<0.001)
Phonophobia
Study 1: S6: 26% vs Pla: 43%
(p<0.001)
Study 2: S6: 20% vs Pla: 56%
(p<0.001)
NRPatient reportNausea
Study 1: S6: 6% vs Pla: 2%
Study 2: S6: 4% vs Pla 2%

Injection site reaction
Study 1: S6: 5% vs Pla: 2%
Study 2: S6: 5% vs Pla: 1%
2 studies

Morning migraines
*

p<0.01 vs placebo

pp<0.05 vs placebo

§

p<0.001 vs placebo

From: Evidence Tables

Cover of Drug Class Review: Triptans
Drug Class Review: Triptans: Final Report Update 4 [Internet].
Helfand M, Peterson K.
Portland (OR): Oregon Health & Science University; 2009 Jun.
Copyright © 2009, Oregon Health & Science University, Portland, Oregon.

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.