Randomized Evaluation of Octreotide Versus Compazine for Emergency Department Treatment of Migraine Headache
Trial Snapshot
- Phase
- Phase 1
- Sponsor
- Enrollment
- 56
- Locations
- 2
- Primary Endpoint
- Patient Satisfaction
Study Overview
Brief Summary
: Headaches are a common complaint presenting to the emergency department (ED), accounting for 1-2% of all ED visits, with migraines as the second most common primary headache syndrome. Patients that ultimately present to the ED have failed outpatient therapy and exhibit severe and persistent symptoms. Treatment options have been traditionally with a parenteral opiod, generally Demerol. Unfortunately, patients with chronic painful conditions like migraines have been prone to dependency. In 1986, a nonopioid, compazine was noted serendipitously to relieve migraine headache pain. 1 Nonopioid regimens have evolved as standard therapy in the treatment of migrainne headache in the ED. Today, there are a number of nonopioid treatment options, but not without their own individual concerns. Ergotamine and dihydroergotamine are effective, but commonly cause nausea and vomiting. Sumatriptan is expensive has recurrence rate, is ineffective in about 20-30%, and is contra-indicated in patients with cardiac disease. Metoclopramide, a dopamine receptor antagonist, commonly used as an anti-emetic agent, has been widely studied for use with acute migraines. Its side effects include drowsiness and dystonic reactions. Compazine has been successfully used to treat migraine headaches for the past several decades, and has been accepted as standard treatment of headaches in the ED. 2 Its side effect profile includes extrapyramidal effects, dysphoria, drowsiness and akathisias. The ideal medication for treating headaches would have no addictive properties, few side effects, quick onset, be highly effective and have a low rate of recurrence. Somatostatin is known to have an inhibitory effect on a number of neuropetides, which have been implicated in migraine. Native somatostatin is an unstable compound and is broken down in minutes, but octreotide, a somatostatin analogue has a longer half life. Intravenous somatostatin has been shown to be as effective as ergotamine in the acute treatment of cluster headache. 3 The analgesic effect of octreotide with headaches associated with growth hormone secreting tumor has been established. 4 Five somatostatin receptors have been cloned with octreotide acting predominantely on sst2 and sst5. The distribution of sst2 within the central nervous system strongly suggests that this particular somatostatin receptor has a role in cranial nociception, being highly expressed in the trigeminal nucleus caudalis and periaqueductal grey. Kapicioglu et.al performed a double blind study comparing octreotide to placebo in treating migraine. They found there to be a significantly greater relief of pain with octreotide at 2 and 6 hours compared to placebo (76% vs 25%, p<0.02). They noted that 47% of those in the octreotide group had complete relief compared to no patients in the placebo group. They went on to note that those patients in the octreotide group had earlier relief of symptoms and no side effects. The only minor adverse event related to the administration of octreotide was a local reaction in 3 patients (18%). In a study performed recently in Netherlands, no clinically relevant changes in vital signs, routine chemistry, and urinalysis were observed with octreotide use. Electrocardiogram analyses showed no newly occurring or worsening of known cardiac abnormalities 2 and 24 h after injection with octreotide. 5 Levy et. al also compared octreotide to placebo in a double blinded study but found no difference. This was a poorly designed study, in that the patients treated themselves at home with an injection of either placebo or octreotide for 2 episodes of headache and recorded their level of pain relief at 2 hours. Matharu et. al also performed a double blind study comparing octreotide to placebo, but looking at cluster headaches rather than migraines. They found there to be a significant improvement with the use of octreotide over placebo (52% vs 36%). At Darnall Army Community Hospital the cost of 100 mcg Octreotide and10 mg Compazine, is $10.46, $2.02-8.00, respectively.
Detailed Description
A urine pregnancy test will be performed on women of child bearing age. After informed consent is obtained, each patient will be placed in a dark private room and asked to grade nausea, pain, and sedation on a 10 cm visual analog scale, using the left end as the zero point for complaints and measurements. Patients will be instructed that a score of zero signifies no pain and a score of 10 indicates severe pain. Each patient will be monitored with continous pulse oximetry and have a 20-gauge IV catheter placed in the antecubital fossa. Based on a computer generated random table, each subject will receive one of the following: 2 cc containing 100ug octreotide, or 10 mg compazine over a 2 minute period, followed by a 5 cc flush of saline solution. The above medication doses were chosen based on previous literature. 6-8 Vital signs (blood pressure, heart rate, and respiratory rate) will be recorded at 0, 30, and 60 minutes. At 60 minutes after the study injection, each patient will be asked to regrade nausea, pain(VAS), and sedation on the same scale without viewing the initial scores. Clinically important successful treatment will be defined as achievement of the following criteria: patient satisfaction and either a decrease of 50% or more in the pain score (compared with the initial score) or an absolute pain score of 2.5 cm or less. Failure to achieve these criteria constitute treatment failure. The treating physician will use an acceptable rescue medicine or group of medicines at treatment failure. The 60 minute outcome was selected because of the route chosen (maximal absorption and distribution within minutes) and because previous published data suggests that most responders are identified during this interval. 9 Each patient will be contacted within 48 hours of discharge to define early relapse rate.
4.8 Inclusion criteria: Adults between the age of 18 and 65 years of age and diagnosis of migraine with or without an aura who met the criteria of the International Headache Society, and with at least one prior episode of a similar headache. 10 The International Headache Society diagnosis criteria for migraine with and without aura is outlined in the below table:
Migraine with AuraØ At least two attacks fulfilling the below characteristicsØ Headache has at least three of the following four characteristics:1. 0ne or more fully reversible aura symptoms indicating focal cerebral cortical and/or brain stem dysfunction2. At least one aura symptom develops gradually over more than 4 minutes, or tow or more symptoms occur in succession3. No aura symptom lasts more than 60 minutes; if more than one aura symptom is present, accepted duration is proportionally increased4. Headache follows aura with a free interval of less than 60 minutes (it may also begin before or simultaneously with the aura) Migraine without AuraØ At least 5 attacks fulfilling the below characteristicsØ Headache attacks lasting 4-72 hours (untreated or unsuccessfully treated)Ø Headache has at least two of the following four characteristics:1. Unilateral location 2. Pulsating quality 3. Moderate or severe intensity which inhibits or prohibits daily activities 4. Aggravated by walking stairs or similar routine physical activityØ During headache at least one of the two following symptoms occur:1. Nausea and/or vomiting2. Photophobia and phonophobia
4.9 Exclusion criteria: pregnancy and lactation, pre-medication within six hours of being enrolled in the study, more than six prior headaches per month, allergy to the study drugs, non-migraine headache, substance abuse, alcohol abuse, diabetes mellitus, or a coexisting condition that might expose the patients to a disproportionately increased risk of a significant adverse event: ischaemic heart disease, peripheral vascular disease, cerebrovascular disease, uncontrolled hypertension (blood pressure >160/95), epilepsy, use of cimetidine, dopamine agonist, cyclopsorin, or oral hypoglycemic agents, hepatic or renal failure, and thyroid disorder.
4.10 Number of Subjects: TOTAL NUMBER OF SUBJECTS (nation-wide/study-wide) 56
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Migraine Headache
Exclusion Criteria
- •Pregnancy and lactation,
- •Pre-medication within six hours of being enrolled in the study,
- •More than six prior headaches per month,
- •Allergy to the study drugs,
- •Non-migraine headache,
- •Substance abuse,
- •Alcohol abuse,
- •Diabetes mellitus, or a coexisting condition that might expose the patients to a disproportionately increased risk of a significant adverse event: ischaemic heart disease, peripheral vascular disease, cerebrovascular disease, uncontrolled hypertension (blood pressure >160/95), epilepsy, use of cimetidine, dopamine agonist, cyclopsorin, or oral hypoglycemic agents, hepatic or renal failure, and thyroid disorder.
Outcomes
Primary Outcomes
Patient Satisfaction
Improvement of Pain
Improvement of Nausea
Secondary Outcomes
No secondary outcomes reported