Clinical trial NCT06868953: Use of the Combination of Sumatriptan and Naproxen in the Acute Treatment of Migraine: Real World Evidence Study
Official title: Use of the Combination of Sumatriptan and Naproxen in the Acute Treatment of Migraine: Real World Evidence Study
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Migraine
Keywords: migraine attack
Lead sponsor: IRCCS San Raffaele Roma
Sponsor class: OTHER
First posted: 2025-03-11
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Consecutive adults with episodic migraine (EM) or chronic migraine (CM) with more than 4 days of migraine per month who attend Headache Centers and have been prescribed at least one dose of sumatriptan 85 mg in combination with naproxen 500 mg for the acute treatment of migraine will be enrolled.

Brief summary: This is a multicenter, observational, prospective, real-life study that will be conducted at Headache Centers, aimed at confirming the efficacy and safety of the combination of sumatriptan 85 mg with naproxen 500 mg. The combination of sumatriptan 85 mg and naproxen sodium 500 mg is indicated for the acute treatment of migraine attacks, with or without aura, in adult patients for whom sumatriptan monotherapy is insufficient. In two randomized studies, the sumatriptan/naproxen sodium combination demonstrated significantly greater efficacy (65% of participants-n=1461-reported pain freedom at 2 hours) compared to sumatriptan alone (55%), naproxen sodium alone (44%), or placebo (28%) when used as a late therapy for a single migraine episode in adults. Similar results were observed in a second study (n=1495), with 57% of participants achieving pain freedom within 2 hours after taking the sumatriptan/naproxen sodium combination, outperforming both sumatriptan monotherapy (50%) and naproxen sodium monotherapy (43%), as well as placebo (29%). This superiority was further assessed through sustained pain freedom over 24 hours, with an efficacy of 23-25% in participants treated with the sumatriptan/naproxen combination compared to placebo (7-8%; p\<0.001 for both studies) and its individual components (sumatriptan monotherapy: 14%-16%; p=0.009 and p\<0.001, naproxen sodium monotherapy: 10%).

In four additional randomized studies, the combination was also found to be effective in menstrual migraine and dysmenorrhea, as well as in cases of poor response or intolerance to triptan therapy. In clinical trials, sumatriptan/naproxen sodium was generally well tolerated, with an overall safety profile similar to that of sumatriptan. The most common adverse events were consistent with those expected for sumatriptan and naproxen sodium.

Detailed description: Consecutive episodic or chronic migraine adults (with more than 4 migraine days per month) followed at the Headache Centers and have been prescribed at least one dose of sumatriptan 85 mg in combination with naproxen sodium 500 mg for the acute treatment of migraine will be enrolled.

The collection of demographic and clinical characteristics will be carried out through a direct interview using a detailed, semi-structured questionnaire during the screening/baseline visit, when the prescription of the sumatriptan 85 mg and naproxen sodium 500 mg combination for migraine attacks will be issued. The follow-up visit will occur after 12 weeks (+/-14 days) from the screening/baseline visit, the end of study visit will take place after 24 weeks (+/-14 days) from baseline.

Patients will be provided with paper diaries for the following 12 weeks at screning/baseline visit and at the follow up visit (at week 12). The paper diaries from the previous 12 weeks will be collected will be collected at week 12 and at week 24.

The following questionnaires will be administered:

* Migraine Specific Quality of Life Questionnaire (MSQ)
* Migraine Interictal Burden Scale (MIBS-4)
* Headache Impact Test-6 (HIT-6) were administered at baseline/screening visit, at follow-up visit (at week 12) and at the end of study visit.

Throughout the study, any adverse events will be recorded and managed.

Eligibility criteria: Inclusion Criteria:

1. Migraineurs (age ≥18 years, \<65 years) with at least 4 migraine days per month according to ICHD-3 criteria who have been prescribed the combination of sumatriptan 85 mg and naproxen 500 mg;
2. Signed informed consent as required;
3. Agreement to comply with all study procedures, including follow-up visits;
4. Use of a contraceptive method by all participants throughout the study duration.

Exclusion Criteria:

1. Age \<18 years or \>65 years
2. Pregnancy or breastfeeding
3. Poor knowledge of the Italian language
4. Comorbidities with other neurological, cardiovascular, hepatic, respiratory, hematological, or autoimmune diseases, or clinically significant laboratory abnormalities
5. Inability to distinguish migraine attacks from tension-type headaches
6. Migraine characterized by mild attacks or attacks that resolve spontaneously within 2 hours
7. Hemiplegic or basilar migraine
8. Headache with the use of acute medication on more than 10 days per month in each of the 3 months prior to screening
9. Unwillingness to participate in the study -

Primary outcomes:
measure: 2 hour-pain freedom
timeFrame: 2 hours after taking combination of sumatriptan 85 mg and naproxen 500 mg
Secondary outcomes:
measure: 1 hour-pain freedom
timeFrame: 1 hour after taking combination of sumatriptan 85 mg and naproxen 500 mg
measure: 2 hour-pain relief
timeFrame: 2 hours after taking combination of sumatriptan 85 mg and naproxen 500 mg
measure: Disappearence of Most Bothersome Symptom
timeFrame: 2 hours after taking combination of sumatriptan 85 mg and naproxen 500 mg
measure: Presence or absence of associated symptoms (nausea, vomiting, photophobia, or phonophobia)
timeFrame: 1-48 hours after taking combination of sumatriptan 85 mg and naproxen 500 mg
measure: 24 hour-sustained pain freedom
timeFrame: 24 hours after taking combination of sumatriptan 85 mg and naproxen 500 mg
measure: 24 hour sustained pain relief
timeFrame: 24 hours after taking combination of sumatriptan 85 mg and naproxen 500 mg
measure: headache recurrence
timeFrame: 2 hours after taking combination of sumatriptan 85 mg and naproxen 500 mg
measure: use of rescue medication
timeFrame: 24 hours after taking combination of sumatriptan 85 mg and naproxen 500 mg
measure: Variation of Migraine Specific Quality of Life Questionnaire score at week 24
timeFrame: week 24 after taking the first dose of combination of sumatriptan 85 mg and naproxen 500 mg
measure: Variation of Migraine Specific Quality of Life Questionnaire score at week 24
timeFrame: week 24 after taking the first dose of combination of sumatriptan 85 mg and naproxen 500 mg
measure: Variation of Migraine Interictal Burden Scale score at week 24
timeFrame: week 24 after taking the first dose of combination of sumatriptan 85 mg and naproxen 500 mg
measure: Variation of Migraine Interictal Burden Scale score at week 24
timeFrame: week 24 after taking the first dose of combination of sumatriptan 85 mg and naproxen 500 mg
measure: Variation of Headache Impact Test score at week 24
timeFrame: week 24 after taking the first dose of combination of sumatriptan 85 mg and naproxen 500 mg
measure: Variation of Headache Impact Test score score at week 24
timeFrame: week 24 after taking the first dose of combination of sumatriptan 85 mg and naproxen 500 mg
measure: Patient Global Impression of Change
timeFrame: week 24 after taking the first dose of combination of sumatriptan 85 mg and naproxen 500 mg
measure: Adverse events occurrence
timeFrame: 48 hours after taking the first dose of combination of sumatriptan 85 mg and naproxen 500 mg
Other outcomes:
Locations:
Study officials:
References:
citation: Brandes JL, Kudrow D, Stark SR, O'Carroll CP, Adelman JU, O'Donnell FJ, Alexander WJ, Spruill SE, Barrett PS, Lener SE. Sumatriptan-naproxen for acute treatment of migraine: a randomized trial. JAMA. 2007 Apr 4;297(13):1443-54. doi: 10.1001/jama.297.13.1443.
citation: Allais G, Castagnoli Gabellari I, Rolando S, Benedetto C. Evaluation of the use of sumatriptan-naproxen sodium for menstrual migraine and dysmenorrhea. Expert Rev Neurother. 2011 Oct;11(10):1383-7. doi: 10.1586/ern.11.123.
citation: Smith TR, Sunshine A, Stark SR, Littlefield DE, Spruill SE, Alexander WJ. Sumatriptan and naproxen sodium for the acute treatment of migraine. Headache. 2005 Sep;45(8):983-91. doi: 10.1111/j.1526-4610.2005.05178.x.
citation: Wilcha RJ, Afridi SK, Barbanti P, Diener HC, Jurgens TP, Lanteri-Minet M, Lucas C, Mawet J, Moisset X, Russo A, Sacco S, Sinclair AJ, Sumelahti ML, Tassorelli C, Goadsby PJ. Sumatriptan-naproxen sodium in migraine: A review. Eur J Neurol. 2024 Sep;31 Suppl 2(Suppl 2):e16434. doi: 10.1111/ene.16434.
citation: Mathew NT, Landy S, Stark S, Tietjen GE, Derosier FJ, White J, Lener SE, Bukenya D. Fixed-dose sumatriptan and naproxen in poor responders to triptans with a short half-life. Headache. 2009 Jul;49(7):971-82. doi: 10.1111/j.1526-4610.2009.01458.x. Epub 2009 May 27.
citation: Silberstein S, McDonald SA, Goldstein J, Aurora S, Lener SE, White J, Runken MC, Saiers J, Derosier F, Lipton RB. Sumatriptan/naproxen sodium for the acute treatment of probable migraine without aura: a randomized study. Cephalalgia. 2014 Apr;34(4):268-79. doi: 10.1177/0333102413508242. Epub 2013 Oct 9.
citation: Lipton RB, Dodick DW, Adelman JU, Kaniecki RG, Lener SE, White JD, Nelsen AC. Consistency of response to sumatriptan/naproxen sodium in a placebo-controlled, crossover study. Cephalalgia. 2009 Aug;29(8):826-36. doi: 10.1111/j.1468-2982.2008.01806.x. Epub 2009 Feb 12.