Pilot Study to Collect and Evaluate Data on the Use of IV* Ibuprofen in the Treatment of an Acute Migraine Attack

Study Overview
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Brief Summary
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This is a pilot trial to collect data on the use of intravenous ibuprofen (IVIb) in the treatment of an acute migraine attack. Data will be collected on the efficacy of IVIb in subjects who are treated with study medication between 2 and 72 hours from time of onset of headache. Periodic safety and efficacy assessments will be performed prior to and after study drug administration. Null hypothesis: There is no difference in the proportion of subjects in the 2 treatment groups (active treatment and placebo) who have pain relief at 2 hours after the completion of the double-blind treatment infusion. Pain relief is defined as a reduction in headache pain level from severe or moderate decreased to mild or headache-free, respectively.

Detailed Description
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This is a 3 visit trial: screening visit, treatment visit, and final visit. Screening visit and a treatment visit may occur on the same day. Additionally, there will be one follow-up phone call at 24 hours post-dose. Subjects will be screened and the investigator will determine whether or not the subject experiences episodic migraine headaches. When a potential subject is seen as an office patient at the Jefferson Headache Center, has a headache, and is referred by the PI or co-investigator to this study, the referring study physician will document that the subject's cognition is intact and the subject is able to understand and sign the informed consent at that time. If the potential subject's cognition is affected by the migraine, the subject must return to the Jefferson Headache Center for the research screening visit when the headache and cognitive difficulties have resolved. Subjects who are not being seen as an office patient on the day of screening must be headache-free at the time of screening. Those subjects who meet the qualifying criteria will be eligible for treatment in the study. Subjects who qualify will be asked to come to the Jefferson Headache Center within 2 to 72 hours following the onset of pain. IVIb or placebo will be administered intravenously as the study treatment. For active treatment, 800 mg of injectable ibuprofen will be placed in 250 ml of normal saline, and infused over 7-10 minutes. (Infusion time may be increased up to 1 hour if necessary due to possible anatomical restrictions). The placebo group will receive 250 ml of normal saline, infused over 7-10 minutes. (Infusion time may be increased up to 1 hour if necessary due to possible anatomical restrictions). Safety and efficacy assessments will be made periodically just prior to and after administration of study drug. Migraine pain and associated symptom assessments will be measured by the subjects for 24 hours from the administration of study drug for the treated attack. If subjects still have a moderate to severe headache at 2 hours after receiving double-blind study drug, they will receive a rescue dose of 800 mg. IV Ibuprofen. Subjects will be discharged at 4 hours post study drug dose, or when clinically indicated.

Official Title
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A Double-blind, Placebo-controlled Pilot Study to Collect and Evaluate Data on the Use of Intravenous Ibuprofen in the Treatment of an Acute Migraine Attack

Conditions
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Episodic Migraine

Intervention / Treatment
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* Other: saline placebo
* Drug: Ibuprofen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects between the ages of 18 and 65, inclusive Subject diagnosed with episodic migraine, with or without aura according to ICHD-2 criteria for at least one-year prior to screening Subject experiences between 2-10 migraine attacks per month (during the previous 6 months) with no more than 15 days of headache per month. Subject is using or agrees to use for the duration of participation a medically acceptable form of contraception (as determined by investigator), if female and of child-bearing potential Subject is able to come for 4 hour in-clinic treatment of an acute migraine attack Subjects are able to understand and comply with all study procedures. Subject provides written informed consent prior to any screening procedures being conducted If subject is on an allowable migraine preventive medication, the dose has been stable for at least 4 weeks prior to screening and the dose will remain stable throughout study participation. Exclusion Criteria: Unable to make a reliable self-report of pain intensity to pain relief Use of analgesic or opioid within 24 hours of onset of headache to be treated with study medication. (If subject has an eligible headache and has taken a triptan or DHE within 24 hours, but greater than 2 hours before study drug dosing, they can be treated with study medication.) Patients taking the following medications on a regular basis: warfarin, lithium, ACE-inhibitors, loop diuretics, thiazide diuretics, ARBs, and methotrexate. Patients with active, clinically significant anemia Patients with a history or evidence of asthma Patients with a history heart failure Subjects with severely impaired hepatic or renal function, as determined by the investigator Patients with a history of allergy or hypersensitivity to any component of IVIb, aspirin (or aspirin related products), NSAIDs, or COX-2 inhibitors Pregnant or nursing women Patients who have a history of congenital bleeding diathesis (e.g., hemophilia) or any active clinically significant bleeding, or have underlying platelet dysfunction including (but not limited to) idiopathic thrombocytopenic purpura, disseminated intravascular coagulation, or congenital platelet dysfunction Patients who have GI bleeding that required medical intervention within the previous 6 weeks (unless definitive surgery has been performed.) Patients who have a platelet count less than 100,000, as determined within the 28 days prior to treatment Pre-existing or current dependence on opioids. Subjects who have participated in an investigational drug trial in the 30 days prior to the screening visit Subjects with uncontrolled hypertension

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: placebo<br>IV saline administration as placebo | Other: saline placebo<br>* 250 cc of placebo administered IV<br>|
| Experimental: Ibuprofen<br>IV ibuprofen | Drug: Ibuprofen<br>* 800 mg ibuprofen in 250 cc saline administered IV<br>* Other names: Caldolor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of Proportion of Subjects in Control and Active Treatment Groups Who Have Pain Relief at 2 Hours After the Completion of the Double-blind Treatment Infusion. | Comparison of proportion of subjects in each treatment group (active treatment and placebo) who have pain relief at 2 hours after the completion of the double-blind treatment infusion. Pain relief is defined as a reduction in headache pain level from severe or moderate decreased to mild or headache-free, respectively. | 2 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Episodic migraine