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

Phase 4

Completed

Conditions: Migraines

Interventions: Drug: Ketorolac
Drug: Sumatriptan
Drug: Placebo

Registration Number: NCT01807234

Lead Sponsor: Johns Hopkins University

Brief 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.

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

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 72

Inclusion Criteria

Not provided

Exclusion Criteria

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
Physician diagnosis of any pain syndrome other than migraine
Classification as treatment resistant by investigator
Known drug or substance abuse
Any opioid use in past 2 months
Use of any medication, which could interfere with study assessments
History of noncompliance with taking medication;
Use of any experimental drug or device within 30 days prior to the Screening Visit (Visit 1);
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.
Any history of chronic renal or hepatic disease already excluded above under number 1; plus see exclusion 9.
History of chronic pulmonary disorder including nasal polyps (see 1) and asthma.
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).
History of nasal surgery.

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Sumatriptan/Placebo	Placebo	Sumatriptan 20 mg single dose nasal spray and placebo
Ketorolac/Placebo	Placebo	Ketorolac 31.5 mg single dose nasal spray and Placebo
Ketorolac Placebo/Sumatriptan placebo	Placebo	single dose Ketorolac placebo, single dose Sumatriptan placebo
Ketorolac/Placebo	Ketorolac	Ketorolac 31.5 mg single dose nasal spray and Placebo
Sumatriptan/Placebo	Sumatriptan	Sumatriptan 20 mg single dose nasal spray and placebo

Primary Outcome Measures

Name	Time	Method
2- Hour Pain Relief	2 hours	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)

Secondary Outcome Measures

Name	Time	Method
Absence of Nausea	2-hours	4) Defined as reduction of nausea to none. Symptom was assessed using a 4-point scale (none, mild, moderate, and severe)
Sustained Pain Relief (SPR)	24 and 48 hours	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).
Absence of Photophobia	2-hours	2) Defined as reduction of photophobia to none. Symptom was assessed using a 4-point scale (none, mild, moderate, and severe)
Absence of Allodynia	2-hours	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.
Absence of Phonophobia	2-hours	3) Defined as reduction of phonophobia to none. Symptom was assessed using a 4-point scale (none, mild, moderate, and severe)
Self-assessment of Disability: Percentage of Participants With Moderate or Severe Disability	2-hours	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 to Pain Relief	following each treated migraine attack	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.
Pain Freedom	2-hours	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).
Sustained Pain Freedom (SPF)	24 and 48 hours	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).