PMID- 30382909 OWN - NLM STAT- MEDLINE DCOM- 20181231 LR - 20200225 IS - 1129-2377 (Electronic) IS - 1129-2369 (Print) IS - 1129-2369 (Linking) VI - 19 IP - 1 DP - 2018 Nov 1 TI - Consistent effects of non-invasive vagus nerve stimulation (nVNS) for the acute treatment of migraine: additional findings from the randomized, sham-controlled, double-blind PRESTO trial. PG - 101 LID - 10.1186/s10194-018-0929-0 [doi] LID - 101 AB - BACKGROUND: Non-invasive vagus nerve stimulation (nVNS) has been shown to be practical, safe, and well tolerated for treating primary headache disorders. The recent multicenter, randomized, double-blind, sham-controlled PRESTO trial provided Class I evidence that for patients with episodic migraine, nVNS significantly increases the probability of having mild pain or being pain-free 2 h post stimulation. We report additional pre-defined secondary and other end points from PRESTO that demonstrate the consistency and durability of nVNS efficacy across a broad range of outcomes. METHODS: After a 4-week observation period, 248 patients with episodic migraine with/without aura were randomly assigned to acute treatment of migraine attacks with nVNS (n = 122) or a sham device (n = 126) during a double-blind period lasting 4 weeks (or until the patient had treated 5 attacks). All patients received nVNS therapy during the subsequent 4-week/5-attack open-label period. RESULTS: The intent-to-treat population consisted of 243 patients. The nVNS group (n = 120) had a significantly greater percentage of attacks treated during the double-blind period that were pain-free at 60 (P = 0.005) and 120 min (P = 0.026) than the sham group (n = 123) did. Similar results were seen for attacks with pain relief at 60 (P = 0.025) and 120 min (P = 0.018). For the first attack and all attacks, the nVNS group had significantly greater decreases (vs sham) in pain score from baseline to 60 min (P = 0.029); the decrease was also significantly greater for nVNS at 120 min for the first attack (P = 0.011). Results during the open-label period were consistent with those of the nVNS group during the double-blind period. The incidence of adverse events (AEs) and adverse device effects was low across all study periods, and no serious AEs occurred. CONCLUSIONS: These results further demonstrate that nVNS is an effective and reliable acute treatment for multiple migraine attacks, which can be used safely while preserving the patient's option to use traditional acute medications as rescue therapy, possibly decreasing the risk of medication overuse. Together with its practicality and optimal tolerability profile, these findings suggest nVNS has value as a front-line option for acute treatment of migraine. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02686034 . FAU - Martelletti, Paolo AU - Martelletti P AD - Department of Clinical and Molecular Medicine, Sapienza University, Rome, Italy. FAU - Barbanti, Piero AU - Barbanti P AD - Headache and Pain Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Pisana, Rome, Italy. FAU - Grazzi, Licia AU - Grazzi L AD - Neuroalgology Unit, Carlo Besta Neurological Institute and Foundation, Milan, Italy. FAU - Pierangeli, Giulia AU - Pierangeli G AD - IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy. FAU - Rainero, Innocenzo AU - Rainero I AD - Department of Neuroscience, University of Turin, Turin, Italy. FAU - Geppetti, Pierangelo AU - Geppetti P AD - Headache Centre, University Hospital of Careggi, Florence, Italy. FAU - Ambrosini, Anna AU - Ambrosini A AD - IRCCS Neuromed, Pozzilli, IS, Italy. FAU - Sarchielli, Paola AU - Sarchielli P AD - Neurologic Clinic, Santa Maria della Misericordia Hospital, Perugia, Italy. FAU - Tassorelli, Cristina AU - Tassorelli C AD - Headache Science Centre, IRCCS C. Mondino Foundation, Pavia, Italy. AD - Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy. FAU - Liebler, Eric AU - Liebler E AD - electroCore, Inc., Basking Ridge, NJ, USA. eric.liebler@electrocore.com. FAU - de Tommaso, Marina AU - de Tommaso M AD - Neurophysiology and Pain Unit, University of Bari Aldo Moro, Bari, Italy. CN - PRESTO Study Group LA - eng SI - ClinicalTrials.gov/NCT02686034 PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20181101 PL - England TA - J Headache Pain JT - The journal of headache and pain JID - 100940562 RN - 0 (Analgesics) SB - IM EIN - J Headache Pain. 2018 Dec 18;19(1):120. PMID: 30563446 MH - Adolescent MH - Adult MH - Aged MH - Analgesics/therapeutic use MH - Double-Blind Method MH - Female MH - Humans MH - Italy/epidemiology MH - Male MH - Middle Aged MH - Migraine Disorders/*diagnosis/epidemiology/*therapy MH - Pain Management/instrumentation/*methods MH - Treatment Outcome MH - Vagus Nerve Stimulation/instrumentation/*methods MH - Young Adult PMC - PMC6755599 OTO - NOTNLM OT - Double-blind OT - Migraine OT - Neuromodulation OT - Open-label OT - Pain intensity OT - Vagus nerve stimulation COIS- P. Martelletti has received research grants, advisory board fees, or travel fees from ACRAF; Allergan S.p.A.; Amgen Inc.; electroCore, Inc.; Novartis AG; and Teva Pharmaceutical Industries Ltd. L. Grazzi has received consultancy and advisory fees from Allergan S.p.A. and electroCore, Inc. G. Pierangeli has nothing to disclose. I. Rainero has received consultancy fees from electroCore, Inc., and Mylan N.V. and research grants from the European Commission - Horizon 2020. He is also a principal investigator for RCTs sponsored by Axovant Sciences Ltd. and TauRx Pharmaceuticals Ltd. P. Geppetti has received consultancy fees from Allergan S.p.A.; electroCore, Inc.; Evidera; Novartis AG; Pfizer Inc.; and Sanofi S.p.A. and research grants from Chiesi Farmaceutici S.p.A. He is also a principal investigator for RCTs sponsored by Eli Lilly and Company; Novartis AG; and Teva Pharmaceutical Industries Ltd. A. Ambrosini has received consultancy fees from Almirall, S.A., and travel grants from Allergan S.p.A., Almirall, S.A., and Novartis. P. Sarchielli has received clinical study fees from Allergan S.p.A. P. Barbanti has received consultancy fees from Allergan S.p.A.; electroCore, Inc.; Janssen Pharmaceuticals, Inc.; Lusofarmaco; and Visufarma and advisory fees from Abbott Laboratories; Merck & Co., Inc.; Novartis AG; and Teva Pharmaceutical Industries Ltd. He is also a principal investigator for RCTs sponsored by Alder BioPharmaceuticals Inc.; Eli Lilly and Company; GlaxoSmithKline Pharmaceuticals Ltd.; and Teva Pharmaceutical Industries Ltd. C. Tassorelli has consulted for Allergan S.p.A.; electroCore, Inc.; Eli Lilly and Company; and Novartis AG and has received research grants from the European Commission and the Italian Ministry of Health. She is also a principal investigator or collaborator for RCTs sponsored by Alder BioPharmaceuticals Inc.; Eli Lilly and Company; Novartis; and Teva Pharmaceutical Industries Ltd. E. Liebler is an employee of electroCore, Inc., and receives stock ownership. M. de Tommaso has received advisory fees from Allergan S.p.A.; Neopharmed; and Pfizer Inc. FIR - Tassorelli, Cristina IR - Tassorelli C FIR - Bitetto, Vito IR - Bitetto V FIR - De Icco, Roberto IR - De Icco R FIR - Martinelli, Daniele IR - Martinelli D FIR - Sances, Grazia IR - Sances G FIR - Bianchi, Monica IR - Bianchi M FIR - Grazzi, Licia IR - Grazzi L FIR - Padovan, Anna Maria IR - Padovan AM FIR - de Tommaso, Marina IR - de Tommaso M FIR - Ricci, Katia IR - Ricci K FIR - Vecchio, Eleonora IR - Vecchio E FIR - Cortelli, Pietro IR - Cortelli P FIR - Cevoli, Sabina IR - Cevoli S FIR - Pierangeli, Giulia IR - Pierangeli G FIR - Terlizzi, Rossana IR - Terlizzi R FIR - Martelletti, Paolo IR - Martelletti P FIR - Negro, Andrea IR - Negro A FIR - Chiariello, Gabriella Addolorata IR - Chiariello GA FIR - Rainero, Innocenzo IR - Rainero I FIR - De Martino, Paola IR - De Martino P FIR - Gai, Annalisa IR - Gai A FIR - Govone, Flora IR - Govone F FIR - Masuzzo, Federica IR - Masuzzo F FIR - Rubino, Elisa IR - Rubino E FIR - Torrieri, Maria Claudia IR - Torrieri MC FIR - Vacca, Alessandro IR - Vacca A FIR - Geppetti, Pierangelo IR - Geppetti P FIR - Chiarugi, Alberto IR - Chiarugi A FIR - De Cesaris, Francesco IR - De Cesaris F FIR - Puma, Simone Li IR - Puma SL FIR - Lupi, Chiara IR - Lupi C FIR - Marone, Ilaria IR - Marone I FIR - Ambrosini, Anna IR - Ambrosini A FIR - Perrotta, Armando IR - Perrotta A FIR - Sarchielli, Paola IR - Sarchielli P FIR - Bernetti, Laura IR - Bernetti L FIR - Corbelli, Ilenia IR - Corbelli I FIR - Romoli, Michele IR - Romoli M FIR - Simoni, Simone IR - Simoni S FIR - Verzina, Angela IR - Verzina A FIR - Barbanti, Piero IR - Barbanti P FIR - Aurilia, Cinzia IR - Aurilia C FIR - Egeo, Gabriella IR - Egeo G FIR - Fofi, Luisa IR - Fofi L FIR - Liebler, Eric IR - Liebler E FIR - Andersson, Annelie IR - Andersson A FIR - Spitzer, Lia IR - Spitzer L FIR - Marin, Juana IR - Marin J FIR - McClure, Candace IR - McClure C FIR - Thackeray, Lisa IR - Thackeray L FIR - Baldi, Maria Giovanna IR - Baldi MG FIR - Di Maro, Daniela IR - Di Maro D EDAT- 2018/11/02 06:00 MHDA- 2019/01/01 06:00 PMCR- 2018/11/01 CRDT- 2018/11/02 06:00 PHST- 2018/08/09 00:00 [received] PHST- 2018/10/03 00:00 [accepted] PHST- 2018/11/02 06:00 [entrez] PHST- 2018/11/02 06:00 [pubmed] PHST- 2019/01/01 06:00 [medline] PHST- 2018/11/01 00:00 [pmc-release] AID - 10.1186/s10194-018-0929-0 [pii] AID - 929 [pii] AID - 10.1186/s10194-018-0929-0 [doi] PST - epublish SO - J Headache Pain. 2018 Nov 1;19(1):101. doi: 10.1186/s10194-018-0929-0.