CONTEXT: Various guidelines recommend different strategies for selecting and sequencing acute treatments for migraine. In step care, treatment is escalated after first-line medications fail. In stratified care, initial treatment is based on measurement of the severity of illness or other factors. These strategies for migraine have not been rigorously evaluated. OBJECTIVE: To compare the clinical benefits of 3 strategies: stratified care, step care within attacks, and step care across attacks, among patients with migraine. DESIGN AND SETTING: Randomized, controlled, parallel-group clinical trial conducted by the Disability in Strategies Study group from December 1997 to March 1999 in 88 clinical centers in 13 countries. PATIENTS: A total of 835 adult migraine patients with a Migraine Disability Assessment Scale (MIDAS) grade of II, III, or IV were analyzed as the efficacy population; the safety analysis included 930 patients. INTERVENTIONS: Patients were randomly assigned to receive (1) stratified care (n = 279), in which patients with MIDAS grade II treated up to 6 attacks with aspirin, 800 to 1000 mg, plus metoclopramide, 10 mg, and patients with MIDAS grade III and IV treated up to 6 attacks with zolmitriptan, 2.5 mg; (2) step care across attacks (n = 271), in which initial treatment was with aspirin, 800 to 1000 mg, plus metoclopramide, 10 mg. Patients not responding in at least 2 of the first 3 attacks switched to zolmitriptan, 2.5 mg, to treat the remaining 3 attacks; and (3) step care within attacks (n = 285), in which initial treatment for all attacks was with aspirin, 800 to 1000 mg, plus metoclopramide, 20 mg. Patients not responding to treatment after 2 hours in each attack escalated treatment to zolmitriptan, 2.5 mg. MAIN OUTCOME MEASURES: Headache response, achieved if pain intensity was reduced from severe or moderate at baseline to mild or no pain at 2 hours; and disability time per treated attack at 4 hours for all 6 attacks, compared among the 3 groups. RESULTS:Headache response at 2 hours was significantly greater across 6 attacks in the stratified care treatment group (52.7%) than in either the step care across attacks group (40.6%; P<.001) or the step care within attacks group (36.4%; P<.001). Disability time (6 attacks) was significantly lower in the stratified care group (mean area under the curve [AUC], 185.0 mm. h) than in the step care across attacks group (mean AUC, 209.4 mm. h; P<.001) or the step care within attacks group (mean AUC, 199.7 mm. h; P<.001). The incidence of adverse events was higher in the stratified care group (321 events) vs both step care groups (159 events in across-attack group; 217 in within-attack group), although most events were of mild-to-moderate intensity. CONCLUSION: Our results indicate that as a treatment strategy, stratified care provides significantly better clinical outcomes than step care strategies within or across attacks as measured by headache response and disability time. JAMA. 2000;284:2599-2605.
RCT Entities:
CONTEXT: Various guidelines recommend different strategies for selecting and sequencing acute treatments for migraine. In step care, treatment is escalated after first-line medications fail. In stratified care, initial treatment is based on measurement of the severity of illness or other factors. These strategies for migraine have not been rigorously evaluated. OBJECTIVE: To compare the clinical benefits of 3 strategies: stratified care, step care within attacks, and step care across attacks, among patients with migraine. DESIGN AND SETTING: Randomized, controlled, parallel-group clinical trial conducted by the Disability in Strategies Study group from December 1997 to March 1999 in 88 clinical centers in 13 countries. PATIENTS: A total of 835 adult migrainepatients with a Migraine Disability Assessment Scale (MIDAS) grade of II, III, or IV were analyzed as the efficacy population; the safety analysis included 930 patients. INTERVENTIONS:Patients were randomly assigned to receive (1) stratified care (n = 279), in which patients with MIDAS grade II treated up to 6 attacks with aspirin, 800 to 1000 mg, plus metoclopramide, 10 mg, and patients with MIDAS grade III and IV treated up to 6 attacks with zolmitriptan, 2.5 mg; (2) step care across attacks (n = 271), in which initial treatment was with aspirin, 800 to 1000 mg, plus metoclopramide, 10 mg. Patients not responding in at least 2 of the first 3 attacks switched to zolmitriptan, 2.5 mg, to treat the remaining 3 attacks; and (3) step care within attacks (n = 285), in which initial treatment for all attacks was with aspirin, 800 to 1000 mg, plus metoclopramide, 20 mg. Patients not responding to treatment after 2 hours in each attack escalated treatment to zolmitriptan, 2.5 mg. MAIN OUTCOME MEASURES: Headache response, achieved if pain intensity was reduced from severe or moderate at baseline to mild or no pain at 2 hours; and disability time per treated attack at 4 hours for all 6 attacks, compared among the 3 groups. RESULTS:Headache response at 2 hours was significantly greater across 6 attacks in the stratified care treatment group (52.7%) than in either the step care across attacks group (40.6%; P<.001) or the step care within attacks group (36.4%; P<.001). Disability time (6 attacks) was significantly lower in the stratified care group (mean area under the curve [AUC], 185.0 mm. h) than in the step care across attacks group (mean AUC, 209.4 mm. h; P<.001) or the step care within attacks group (mean AUC, 199.7 mm. h; P<.001). The incidence of adverse events was higher in the stratified care group (321 events) vs both step care groups (159 events in across-attack group; 217 in within-attack group), although most events were of mild-to-moderate intensity. CONCLUSION: Our results indicate that as a treatment strategy, stratified care provides significantly better clinical outcomes than step care strategies within or across attacks as measured by headache response and disability time. JAMA. 2000;284:2599-2605.