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CompletedNCT01807234KSPNUpdated Mar 13, 2017Results posted

Comparison of Ketorolac Nasal Spray to Sumatriptan Nasal Spray and Placebo for Acute Treatment of Migraine

A Phase 4 interventional study of Ketorolac and Sumatriptan in Migraines, sponsored by Johns Hopkins University. Completed at 1 site in United States. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2017-03-13.

Sponsored by Johns Hopkins University · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
72
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
All
01

Study summary

The investigators propose to test the efficacy of ketorolac nasal spray versus sumatriptan nasal spray versus placebo for acute abortive therapy of migraine head pain as well as for migraine associated symptoms including nausea and allodynia.

Read the detailed description

Participants are randomized to Ketorolac NS 31.5 mg, Sumatriptan NS 20 mg or placebo to treat three moderate to severe migraine attacks and switched treatments with each attack so that they received each treatment only once.

For each treated attack (moderate to severe migraine attack), participants utilized two study treatments (A and B). Study treatment A administered as one spray in each nostril, and study treatment B administered as one spray in one nostril.

Randomized to Ketorolac, A=Ketorolac, B=Placebo Randomized to Sumatriptan, A=Placebo, B=Sumatriptan Randomized to Placebo, A=Placebo, B=Placebo

02

Conditions studied

  • Migraines

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03

In context

Migraine Disorders

1,528 studies on the registry are indexed under Migraine Disorders; 299 are open to participants now.

This study's enrollment of 72 is close to the median of 80 across 1,175 interventional studies indexed under Migraine Disorders.

Browse Migraine Disorders studies →

Lead sponsor

Johns Hopkins University is the lead sponsor of 1,783 studies on the registry; 313 are open to participants now.

Of its 203 completed or terminated interventional studies of FDA-regulated products, 140 (69%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

At the Screening Visit, a subject must meet the following criteria to participate in this study:

1.18-65 years of age 2.Fulfills International Classification of Headache Disorders (ICHD)-II Criteria of migraine as noted below in Table 1 3.History of migraines for at least one year 4.Migraine onset prior to the age of 50 years of age 5.Headache frequency (of any headaches, migraine or non-migraine) \< 9 days per month 6.At visit 2, participants must report two or more headache days during the 28-day run-in period on the headache diary. 7.At least 48 hours of freedom from headache between treated migraine attacks. 8.If currently using headache preventive medications, must be on a stable dose for at least 3 months prior to enrollment and throughout the study period and be on no more than one prophylactic agent. 9.Able to complete all study procedures, including the questionnaire (assessing demographics, headache characteristics, headache comorbidities and medical history at the initial visit and headache characteristics) and the required headache calendars, and all study visits; 10.Able to understand, read and sign an informed consent (English).

Exclusion criteria

Exclusion Criteria:

  1. Any condition (history or presence of) which contraindicates the use of triptans or NSAIDs including:

    • Known hypersensitivity or intolerance to triptans or NSAIDs
    • Contraindications to triptan use (uncontrolled hypertension, ischemic heart disease, prinz-metal angina, cardiac arrhythmias, multiple risk factors for atherosclerotic vascular disease, primary vasculopathies, and basilar and hemiplegic migraine)
    • Cerebrovascular disease except for mild non-specific white matter disease
    • Peripheral vascular disease or any other ischemic disease including myocardial infarction
    • Uncontrolled hypertension (systolic BP 160 mmHg or diastolic BP 95 mmHg or (both)
    • Migraine aura fulfilling ICHD-II criteria for hemiplegic or basilar-type migraine
    • Any history of chronic renal or hepatic impairment
    • Use of an ergotamine-containing medication or monamine oxidase inhibitor
    • Known or suspected pregnancy, negative pregnancy test
    • Lactation
    • Bleeding dsycrasias including gastritis, peptic ulcer disease,gastrointestinal bleeding
  2. Physician diagnosis of any pain syndrome other than migraine
  3. Classification as treatment resistant by investigator
  4. Known drug or substance abuse
  5. Any opioid use in past 2 months
  6. Use of any medication, which could interfere with study assessments
  7. History of noncompliance with taking medication;
  8. Use of any experimental drug or device within 30 days prior to the Screening Visit (Visit 1);
  9. Any abnormal finding or condition deemed clinically significant by the investigator on history, screening, or physical exam that contraindicates the use of triptans or NSAIDs or that might interfere with the patient's safety, study participation, or which might confound the interpretation of the study results.
  10. Any history of chronic renal or hepatic disease already excluded above under number 1; plus see exclusion 9.
  11. History of chronic pulmonary disorder including nasal polyps (see 1) and asthma.
  12. History of upper respiratory infection or other respiratory tract condition that could interfere with the absorption of the nasal spray or with assessment of AEs including rhinitis medicamentosa (chronic daily use of topical decongestants).
  13. History of nasal surgery.
05

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
Double (Participant, Investigator)
Enrollment
72 participants (actual)

Study arms

  • Experimental
    Ketorolac/Placebo

    Ketorolac 31.5 mg single dose nasal spray and Placebo

    Drug: Ketorolac · Drug: Placebo

  • Experimental
    Sumatriptan/Placebo

    Sumatriptan 20 mg single dose nasal spray and placebo

    Drug: Sumatriptan · Drug: Placebo

  • Placebo comparator
    Ketorolac Placebo/Sumatriptan placebo

    single dose Ketorolac placebo, single dose Sumatriptan placebo

    Drug: Placebo

Interventions

  • DrugKetorolac

    Single dose of Ketorolac (Sprix) nasal spray 31.5 mg, one spray in each nostril for an acute migraine attack.

    Also known as: Sprix

  • DrugSumatriptan

    Sumatriptan (Imitrex) 20 mg one single dose of nasal spray for an acute migraine attack.

    Also known as: Imitrex

  • DrugPlacebo

    Placebo one spray in each nostril and placebo one nasal spray.

06

What researchers measure

Primary outcomes

  1. 2- Hour Pain Relief

    The primary outcome was 2-hour headache relief; headache relief was defined as headache pain from moderate or severe pain to none or mild pain. Pain was assessed using a 4-point scale (none, mild, moderate, and severe)

    Time frame: 2 hours

Secondary outcomes

  1. Pain Freedom

    1) Pain Freedom: Pain Freedom at 2 hours is defined as being free of pain. Pain was assessed using a 4-point scale (none, mild, moderate, and severe).

    Time frame: 2-hours

  2. Absence of Photophobia

    2) Defined as reduction of photophobia to none. Symptom was assessed using a 4-point scale (none, mild, moderate, and severe)

    Time frame: 2-hours

  3. Absence of Phonophobia

    3) Defined as reduction of phonophobia to none. Symptom was assessed using a 4-point scale (none, mild, moderate, and severe)

    Time frame: 2-hours

  4. Absence of Nausea

    4) Defined as reduction of nausea to none. Symptom was assessed using a 4-point scale (none, mild, moderate, and severe)

    Time frame: 2-hours

  5. Absence of Allodynia

    5) Absence of allodynia The presence of allodynia was assessed based on a series of 8 questions inquiring as to the presence of allodynia. Participants answering 2 or more questions positively were considered to have allodynia.

    Time frame: 2-hours

  6. Self-assessment of Disability: Percentage of Participants With Moderate or Severe Disability

    Participants' self-assessment of disability was assessed using 4-point scales (none, mild, moderate, and severe). A binary outcome variable was created grouping none and mild vs moderate to severe. .

    Time frame: 2-hours

  7. Sustained Pain Relief (SPR)

    7) 24 and 48 hours sustained pain relief (SPR) Defined as the reduction of pain to none or mild from moderate or severe, on a 4-point scale (none, mild, moderate, and severe).

    Time frame: 24 and 48 hours

  8. Sustained Pain Freedom (SPF)

    8) 24 and 48 hours sustained pain freedom (SPF); Defined as the reduction of pain to none. Pain was assessed using a 4-point scale (none, mild, moderate, and severe).

    Time frame: 24 and 48 hours

  9. Time to Pain Relief

    9) The time, in minutes, will be measured from the time study drug is taken to the time when significant pain relief is first observed and maintained through 2 hours with no rescue medication use at or prior to this point.

    Time frame: following each treated migraine attack

07

Results

Posted Mar 13, 2017
Limitations and caveats
Small study size (n=54)

Participant flow

Participant flow — Overall Study
MilestoneKetorolac Then Sumatriptan Then PlaceboKerorolac Then Placebo Then SumatriptanSumatriptan Then Ketorolac Then PlaceboSumatriptan Then Placebo Then KetorolacPlacebo Then Ketorolac Then SumatriptanPlacebo Then Sumatriptan Then Ketorolac
Started121212121212
Randomized, but did not take drug352143
Completed only 1 attack210101
Completed76101088
Not completed562244
Withdrew: Lost to follow-up251112
Withdrew: Withdrawal by subject311121
Withdrew: Lack of efficacy000011

Outcome measures

Primary2- Hour Pain Relief

The primary outcome was 2-hour headache relief; headache relief was defined as headache pain from moderate or severe pain to none or mild pain. Pain was assessed using a 4-point scale (none, mild, moderate, and severe)

Time frame:
2 hours
Reported as:
Number · percentage of participants
2- Hour Pain Relief
percentage of participantsKetorolac/ PlaceboSumatriptan/ PlaceboKetorolac Placebo/ Sumatriptan Placebo
2- Hour Pain Relief72.5 (59.9 to 85.2)69.4 (56.0 to 82.8)38.8 (24.6 to 52.9)
SecondaryPain Freedom

1) Pain Freedom: Pain Freedom at 2 hours is defined as being free of pain. Pain was assessed using a 4-point scale (none, mild, moderate, and severe).

Time frame:
2-hours
Reported as:
Number · percentage of patients
Pain Freedom
percentage of patientsKetorolac/ PlaceboSumatriptan/PlaceboKetorolac Placebo/ Sumatriptan Placebo
Pain Freedom43.1 (29.1 to 57.2)36.7 (22.7 to 50.7)18.4 (7.1 to 29.6)
SecondaryAbsence of Photophobia

2) Defined as reduction of photophobia to none. Symptom was assessed using a 4-point scale (none, mild, moderate, and severe)

Time frame:
2-hours
Reported as:
Number · percentage of patients
Absence of Photophobia
percentage of patientsKetorolac/ PlaceboSumatriptan/ PlaceboKetorolac Placebo/ Sumatriptan Placebo
Absence of Photophobia65.4 (56.1 to 74.7)64.0 (54.4 to 73.6)46.0 (36.1 to 55.9)
SecondaryAbsence of Phonophobia

3) Defined as reduction of phonophobia to none. Symptom was assessed using a 4-point scale (none, mild, moderate, and severe)

Time frame:
2-hours
Reported as:
Number · percentage of patients
Absence of Phonophobia
percentage of patientsKetorolac/ PlaceboSumatriptan/PlaceboKetorolac Placebo/ Sumatriptan Placebo
Absence of Phonophobia75.0 (66.5 to 83.4)66.0 (56.5 to 75.4)56.0 (46.1 to 65.9)
SecondaryAbsence of Nausea

4) Defined as reduction of nausea to none. Symptom was assessed using a 4-point scale (none, mild, moderate, and severe)

Time frame:
2-hours
Reported as:
Number · percentage of patients
Absence of Nausea
percentage of patientsKetorolac/ PlaceboSumatriptan/ PlaceboKetorolac Placebo/ Sumatriptan Placebo
Absence of Nausea82.7 (75.3 to 90.0)74.0 (65.2 to 82.7)66.0 (56.5 to 75.4)
SecondaryAbsence of Allodynia

5) Absence of allodynia The presence of allodynia was assessed based on a series of 8 questions inquiring as to the presence of allodynia. Participants answering 2 or more questions positively were considered to have allodynia.

Time frame:
2-hours
Reported as:
Number · percentage of patients
Absence of Allodynia
percentage of patientsKetorolac/ PlaceboSumatriptan/ PlaceboKetorolac Placebo/ Sumatriptan Placebo
Absence of Allodynia70.5 (57.6 to 83.5)75.5 (63.0 to 87.9)69.0 (57.6 to 83.5)
SecondarySelf-assessment of Disability: Percentage of Participants With Moderate or Severe Disability

Participants' self-assessment of disability was assessed using 4-point scales (none, mild, moderate, and severe). A binary outcome variable was created grouping none and mild vs moderate to severe. .

Time frame:
2-hours
Reported as:
Number · percentage of patients
Self-assessment of Disability: Percentage of Participants With Moderate or Severe Disability
percentage of patientsKetorolac/ PlaceboSumatriptan/ PlaceboKetorolac Placebo/ Sumatriptan Placebo
Self-assessment of Disability: Percentage of Participants With Moderate or Severe Disability1.9 (0.2 to 13.1)8.1 (3.0 to 20.1)10.2 (4.2 to 22.5)
SecondarySustained Pain Relief (SPR)

7) 24 and 48 hours sustained pain relief (SPR) Defined as the reduction of pain to none or mild from moderate or severe, on a 4-point scale (none, mild, moderate, and severe).

Time frame:
24 and 48 hours
Reported as:
Number · percentage of patients
Sustained Pain Relief (SPR)
percentage of patientsKetorolac/ PlaceboSumatriptan/ PlaceboKetorolac Placebo/ Sumatriptan Placebo
24 hour sustained pain relief49.0 (34.8 to 63.2)40.8 (26.5 to 55.1)20.4 (8.7 to 32.1)
48 hour sustained pain relief49.0 (34.8 to 63.2)30.6 (17.2 to 43.9)20.4 (8.7 to 32.1)
SecondarySustained Pain Freedom (SPF)

8) 24 and 48 hours sustained pain freedom (SPF); Defined as the reduction of pain to none. Pain was assessed using a 4-point scale (none, mild, moderate, and severe).

Time frame:
24 and 48 hours
Reported as:
Number · percentage of patients
Sustained Pain Freedom (SPF)
percentage of patientsKetorolac/ PlaceboSumatriptan/ PlaceboKetorolac Placebo/ Sumatriptan Placebo
24 hour sustained pain freedom35.3 (21.7 to 48.9)22.4 (10.3 to 34.5)12.2 (2.7 to 21.7)
48 hour sustained pain freedom33.3 (19.9 to 46.7)18.4 (7.1 to 29.6)12.2 (2.7 to 21.7)
SecondaryTime to Pain Relief

9) The time, in minutes, will be measured from the time study drug is taken to the time when significant pain relief is first observed and maintained through 2 hours with no rescue medication use at or prior to this point.

Time frame:
following each treated migraine attack
Reported as:
Number · percentage of patients
Time to Pain Relief
percentage of patientsKetorolac/ PlaceboSumatriptan/ PlaceboKetorolac Placebo/ Sumatriptan Placebo
10 minutes15.7 (5.3 to 26.0)14.3 (4.1 to 24.4)12.2 (2.7 to 21.7)
15 minutes35.3 (21.7 to 48.8)36.0 (22.2 to 49.7)14.3 (4.1 to 24.4)
20 minutes43.1 (29.1 to 57.2)44.9 (30.4 to 59.3)22.4 (10.3 to 34.5)
30 minutes54.9 (40.7 to 69.0)53.1 (38.6 to 67.5)26.5 (13.7 to 39.3)
1 hour58.8 (44.8 to 72.8)57.1 (42.8 to 71.5)32.6 (19.0 to 46.2)

Adverse events

Collected over Adverse event data was collected at the 10 minute, 15 minute, 20 minute, 30 minute, 60 minute, 2 hour, 24 hour and 72 hour mark.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Sprix/Placebo—0/52 (0%)43/52 (82.7%)
Sumatriptan/Placebo—0/50 (0%)39/50 (78%)
SRIX Placebo/Sumatriptan Placebo—0/50 (0%)11/50 (22%)
Most frequent other events
Showing 10 of 12
Most frequent other events
EventSprix/PlaceboSumatriptan/PlaceboSRIX Placebo/Sumatriptan Placebo
mild burning of noseRespiratory, thoracic and mediastinal disorders13/523/501/50
mild unusual tasteNervous system disorders1/5212/502/50
moderate burning of noseRespiratory, thoracic and mediastinal disorders10/521/500/50
moderate unusual tasteNervous system disorders3/526/501/50
nauseaGastrointestinal disorders1/524/502/50
nasal discomfortRespiratory, thoracic and mediastinal disorders4/523/500/50
burning of throatRespiratory, thoracic and mediastinal disorders3/523/500/50
severe unusual tasteNervous system disorders1/522/500/50
fatigueGeneral disorders2/522/502/50
dizzinessNervous system disorders2/522/501/50

Baseline characteristics

Of the 72 randomized participants, 54 (75%) treated at least one attack and 49 (68%) completed all three treatments, for a total of 152 treated migraine attacks.

Age, Categorical
Age, Categorical(Participants)Ketorolac Then Sumatriptan Then PlaceboKetorolac Then Placebo Then SumatriptanSumatriptan Then Ketorolac Then PlaceboSumatriptan Then Placebo Then KetorolacPlacebo Then Ketorolac Then SumatriptanPlacebo Then Sumatriptan Then KetorolacTotal
<=18 years0000000
Between 18 and 65 years12121212121272
>=65 years0000000
Age, Continuous
Age, Continuous(years)Ketorolac Then Sumatriptan Then PlaceboKetorolac Then Placebo Then SumatriptanSumatriptan Then Ketorolac Then PlaceboSumatriptan Then Placebo Then KetorolacPlacebo Then Ketorolac Then SumatriptanPlacebo Then Sumatriptan Then KetorolacTotal
Mean36.3 ± 9.836.3 ± 9.836.3 ± 9.836.3 ± 9.836.3 ± 9.836.3 ± 9.836.3 ± 9.8
Sex: Female, Male
Sex: Female, Male(Participants)Ketorolac Then Sumatriptan Then PlaceboKetorolac Then Placebo Then SumatriptanSumatriptan Then Ketorolac Then PlaceboSumatriptan Then Placebo Then KetorolacPlacebo Then Ketorolac Then SumatriptanPlacebo Then Sumatriptan Then KetorolacTotal
Female11121212121170
Male1000012
Region of Enrollment
Region of Enrollment(participants)Ketorolac Then Sumatriptan Then PlaceboKetorolac Then Placebo Then SumatriptanSumatriptan Then Ketorolac Then PlaceboSumatriptan Then Placebo Then KetorolacPlacebo Then Ketorolac Then SumatriptanPlacebo Then Sumatriptan Then KetorolacTotal
United States12121212121272
08

Study locations

1 site
  • The Johns Hopkins Bayview Headache Center
    Baltimore, Maryland 21224, United States
09

References and documents

Publications

  • Rao AS, Gelaye B, Kurth T, Dash PD, Nitchie H, Peterlin BL. A Randomized Trial of Ketorolac vs. Sumatripan vs. Placebo Nasal Spray (KSPN) for Acute Migraine. Headache. 2016 Feb;56(2):331-40. doi: 10.1111/head.12767. Epub 2016 Feb 3. PubMed 26840902 ↗

Individual participant data

Plan to share: Undecided

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 13, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01807234
Lead sponsor
Johns Hopkins University
Collaborators
American Regent, Inc.
Responsible party
Drs Barbara Peterlin (Director, The Johns Hopkins Bayview Headache Research, Johns Hopkins University) — Principal investigator
First posted
Mar 8, 2013
Start date
Feb 2013
Primary completion
Dec 2014
Completion
Dec 2014
Results posted
Mar 13, 2017
Last update
Mar 13, 2017

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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