Efficacy of naloxone in reducing postictal central respiratory dysfunction in patients with epilepsy: study protocol for a double-blind, randomized, placebo-controlled trial
Generalized tonic-clonic seizures (GTCSs) are the main risk factor for sudden unexpected death in epilepsy (SUDEP). Experimental and clinical data strongly suggest that the majority of SUDEP results from a postictal respiratory dysfunction progressing to terminal apnea. Postictal apnea could partly...
Gespeichert in:
| Veröffentlicht in: | Current controlled trials in cardiovascular medicine 2016-11, Vol.17 (1), p.529-529, Article 529 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 529 |
|---|---|
| container_issue | 1 |
| container_start_page | 529 |
| container_title | Current controlled trials in cardiovascular medicine |
| container_volume | 17 |
| creator | Rheims, Sylvain Valton, Luc Michel, Véronique Maillard, Louis Navarro, Vincent Convers, Philippe Bartolomei, Fabrice Biraben, Arnaud Crespel, Arielle Derambure, Philippe de Toffol, Bertrand Hirsch, Edouard Kahane, Philippe Martin, Martine Lemesle Tourniaire, Didier Boulogne, Sébastien Mercier, Catherine Roy, Pascal Ryvlin, Philippe |
| description | Generalized tonic-clonic seizures (GTCSs) are the main risk factor for sudden unexpected death in epilepsy (SUDEP). Experimental and clinical data strongly suggest that the majority of SUDEP results from a postictal respiratory dysfunction progressing to terminal apnea. Postictal apnea could partly derive from a seizure-induced massive release of endogenous opioids. The main objective of this study is to evaluate the efficacy of an opioid antagonist, naloxone, administered in the immediate aftermath of a GTCS, in reducing the severity of the postictal central respiratory dysfunction.
The Efficacy of Naloxone in Reducing Postictal Central Respiratory Dysfunction in Patients with Epilepsy (ENALEPSY) study is a multicenter, double-blind, randomized, placebo-controlled trial conducted in patients with drug-resistant focal epilepsy who are undergoing long-term video-electroencephalogram (EEG) monitoring (LTM) in an epilepsy monitoring unit (EMU). We plan to randomize 166 patients (1:1) to receive intravenous naloxone (0.4 mg) or placebo in the immediate aftermath of a GTCS. Because inclusion in the study needs to take place prior to the occurrence of the GTCS, and because such occurrence is observed in about one-fourth of patients undergoing LTM, we plan to include a maximum of 700 patients upon admission in the EMU. The primary endpoint will be the proportion of patients whose oxygen saturation is |
| doi_str_mv | 10.1186/s13063-016-1653-1 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5094038</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2795253644</sourcerecordid><originalsourceid>FETCH-LOGICAL-c461t-f2b820646857aa8a853c6247ce3d70b8d3bd2b1102bdbb9ce32ddd51189f352f3</originalsourceid><addsrcrecordid>eNpdUl1rFTEQXUSxtfoDfJGALwqu5nuzfRBKqVa44Is-h3xtm5KbrEm2uv4n_6O53GupfZph5pyZM8npupcIvkdI8A8FEchJDxHvEWekR4-6YzRQ1nOM2ON7-VH3rJQbCCkZCX3aHeFBwFFwcdz9uZgmb5RZQZpAVCH9StEBH0F2djE-XoE5lepNVQEYF2tuMbsy-6xqyiuwa5mWaKpPcceaVfUNVcBPX6-Bm31wc1lPQamLXcGcU00mBTClDBSwadHB9Tr4aN-BrKJNW__btXwOyjidepPaxhSCs6Bmr8Lz7smkQnEvDvGk-_7p4tv5Zb_5-vnL-dmmN5Sj2k9YCww55YINSgklGDEc08E4YgeohSXaYo0QxNpqPbYyttay9qbjRBieyEn3cT93XvTW2cPhcs5-q_Iqk_Ly_0701_Iq3UoGRwqJaAPe7gdcP6Bdnm3krgYRhXQU7BY17JvDspx-LK5UufXFuBBUdGkpEgnCBzwOI2zQ1w-gN2nJ7duKxMPIMCOc0oZCe5TJqZTspjsFCMqdceTeOE0ElzvjyJ2IV_cvvmP8cwr5C7dgwy4</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2795253644</pqid></control><display><type>article</type><title>Efficacy of naloxone in reducing postictal central respiratory dysfunction in patients with epilepsy: study protocol for a double-blind, randomized, placebo-controlled trial</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>PubMed Central Open Access</source><source>Springer Nature OA Free Journals</source><source>Springer Nature - Complete Springer Journals</source><source>PubMed Central</source><creator>Rheims, Sylvain ; Valton, Luc ; Michel, Véronique ; Maillard, Louis ; Navarro, Vincent ; Convers, Philippe ; Bartolomei, Fabrice ; Biraben, Arnaud ; Crespel, Arielle ; Derambure, Philippe ; de Toffol, Bertrand ; Hirsch, Edouard ; Kahane, Philippe ; Martin, Martine Lemesle ; Tourniaire, Didier ; Boulogne, Sébastien ; Mercier, Catherine ; Roy, Pascal ; Ryvlin, Philippe</creator><creatorcontrib>Rheims, Sylvain ; Valton, Luc ; Michel, Véronique ; Maillard, Louis ; Navarro, Vincent ; Convers, Philippe ; Bartolomei, Fabrice ; Biraben, Arnaud ; Crespel, Arielle ; Derambure, Philippe ; de Toffol, Bertrand ; Hirsch, Edouard ; Kahane, Philippe ; Martin, Martine Lemesle ; Tourniaire, Didier ; Boulogne, Sébastien ; Mercier, Catherine ; Roy, Pascal ; Ryvlin, Philippe ; ENALEPSY study group ; on behalf of ENALEPSY study group</creatorcontrib><description>Generalized tonic-clonic seizures (GTCSs) are the main risk factor for sudden unexpected death in epilepsy (SUDEP). Experimental and clinical data strongly suggest that the majority of SUDEP results from a postictal respiratory dysfunction progressing to terminal apnea. Postictal apnea could partly derive from a seizure-induced massive release of endogenous opioids. The main objective of this study is to evaluate the efficacy of an opioid antagonist, naloxone, administered in the immediate aftermath of a GTCS, in reducing the severity of the postictal central respiratory dysfunction.
The Efficacy of Naloxone in Reducing Postictal Central Respiratory Dysfunction in Patients with Epilepsy (ENALEPSY) study is a multicenter, double-blind, randomized, placebo-controlled trial conducted in patients with drug-resistant focal epilepsy who are undergoing long-term video-electroencephalogram (EEG) monitoring (LTM) in an epilepsy monitoring unit (EMU). We plan to randomize 166 patients (1:1) to receive intravenous naloxone (0.4 mg) or placebo in the immediate aftermath of a GTCS. Because inclusion in the study needs to take place prior to the occurrence of the GTCS, and because such occurrence is observed in about one-fourth of patients undergoing LTM, we plan to include a maximum of 700 patients upon admission in the EMU. The primary endpoint will be the proportion of patients whose oxygen saturation is <90 % between 1 and 3 min after the end of a GTCS. Secondary outcomes will include the following: the proportion of patients who show postictal apnea, the occurrence and duration of postictal generalized EEG suppression, the total duration of the postictal coma, postictal pain, and the number of patients who have a second GTCS within 120 min after the intravenous injection.
The demonstration of naloxone's efficacy on the severity of postictal hypoxemia will have two primary consequences. First, naloxone would be the first and only therapeutic approach that could be delivered immediately to reverse postictal apnea. Second, demonstration that an opioid antagonist can effectively reduce postictal apnea would pave the way for an assessment of a preventive therapy for SUDEP targeting the same pathophysiological pathway using oral administration of naltrexone.
ClinicalTrials.gov identifier: NCT02332447 . Registered on 5 January 2015.</description><identifier>ISSN: 1745-6215</identifier><identifier>EISSN: 1745-6215</identifier><identifier>DOI: 10.1186/s13063-016-1653-1</identifier><identifier>PMID: 27809868</identifier><language>eng</language><publisher>England: BioMed Central</publisher><subject>Clinical Protocols ; Convulsions & seizures ; Double-Blind Method ; Double-blind studies ; Drug Administration Schedule ; Drug overdose ; Drug resistance ; Electroencephalography ; Electroencephalography - methods ; Epilepsy ; France ; Humans ; Hypotheses ; Hypoxemia ; Hypoxia - etiology ; Hypoxia - physiopathology ; Hypoxia - prevention & control ; Injections, Intravenous ; Life Sciences ; Medication ; Naloxone - administration & dosage ; Naloxone - adverse effects ; Narcotic Antagonists - administration & dosage ; Narcotic Antagonists - adverse effects ; Narcotics ; Neurobiology ; Neurons and Cognition ; Oxygen saturation ; Patients ; Pharmaceutical sciences ; Pharmaceuticals ; Pulse oximetry ; Research Design ; Respiratory Center - drug effects ; Respiratory Center - physiopathology ; Respiratory Insufficiency - diagnosis ; Respiratory Insufficiency - etiology ; Respiratory Insufficiency - physiopathology ; Respiratory Insufficiency - prevention & control ; Seizures - complications ; Seizures - diagnosis ; Seizures - drug therapy ; Seizures - physiopathology ; Severity of Illness Index ; Study Protocol ; Time Factors ; Treatment Outcome ; Young adults</subject><ispartof>Current controlled trials in cardiovascular medicine, 2016-11, Vol.17 (1), p.529-529, Article 529</ispartof><rights>The Author(s). 2016. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Attribution</rights><rights>The Author(s). 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c461t-f2b820646857aa8a853c6247ce3d70b8d3bd2b1102bdbb9ce32ddd51189f352f3</citedby><cites>FETCH-LOGICAL-c461t-f2b820646857aa8a853c6247ce3d70b8d3bd2b1102bdbb9ce32ddd51189f352f3</cites><orcidid>0000-0002-1678-0297 ; 0000-0001-6718-8210 ; 0000-0003-4906-6855 ; 0000-0001-8681-7369 ; 0000-0003-3837-3198 ; 0000-0002-4663-8515 ; 0000-0003-0077-8114</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5094038/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5094038/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,725,778,782,862,883,27913,27914,53780,53782</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27809868$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.sorbonne-universite.fr/hal-01404985$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Rheims, Sylvain</creatorcontrib><creatorcontrib>Valton, Luc</creatorcontrib><creatorcontrib>Michel, Véronique</creatorcontrib><creatorcontrib>Maillard, Louis</creatorcontrib><creatorcontrib>Navarro, Vincent</creatorcontrib><creatorcontrib>Convers, Philippe</creatorcontrib><creatorcontrib>Bartolomei, Fabrice</creatorcontrib><creatorcontrib>Biraben, Arnaud</creatorcontrib><creatorcontrib>Crespel, Arielle</creatorcontrib><creatorcontrib>Derambure, Philippe</creatorcontrib><creatorcontrib>de Toffol, Bertrand</creatorcontrib><creatorcontrib>Hirsch, Edouard</creatorcontrib><creatorcontrib>Kahane, Philippe</creatorcontrib><creatorcontrib>Martin, Martine Lemesle</creatorcontrib><creatorcontrib>Tourniaire, Didier</creatorcontrib><creatorcontrib>Boulogne, Sébastien</creatorcontrib><creatorcontrib>Mercier, Catherine</creatorcontrib><creatorcontrib>Roy, Pascal</creatorcontrib><creatorcontrib>Ryvlin, Philippe</creatorcontrib><creatorcontrib>ENALEPSY study group</creatorcontrib><creatorcontrib>on behalf of ENALEPSY study group</creatorcontrib><title>Efficacy of naloxone in reducing postictal central respiratory dysfunction in patients with epilepsy: study protocol for a double-blind, randomized, placebo-controlled trial</title><title>Current controlled trials in cardiovascular medicine</title><addtitle>Trials</addtitle><description>Generalized tonic-clonic seizures (GTCSs) are the main risk factor for sudden unexpected death in epilepsy (SUDEP). Experimental and clinical data strongly suggest that the majority of SUDEP results from a postictal respiratory dysfunction progressing to terminal apnea. Postictal apnea could partly derive from a seizure-induced massive release of endogenous opioids. The main objective of this study is to evaluate the efficacy of an opioid antagonist, naloxone, administered in the immediate aftermath of a GTCS, in reducing the severity of the postictal central respiratory dysfunction.
The Efficacy of Naloxone in Reducing Postictal Central Respiratory Dysfunction in Patients with Epilepsy (ENALEPSY) study is a multicenter, double-blind, randomized, placebo-controlled trial conducted in patients with drug-resistant focal epilepsy who are undergoing long-term video-electroencephalogram (EEG) monitoring (LTM) in an epilepsy monitoring unit (EMU). We plan to randomize 166 patients (1:1) to receive intravenous naloxone (0.4 mg) or placebo in the immediate aftermath of a GTCS. Because inclusion in the study needs to take place prior to the occurrence of the GTCS, and because such occurrence is observed in about one-fourth of patients undergoing LTM, we plan to include a maximum of 700 patients upon admission in the EMU. The primary endpoint will be the proportion of patients whose oxygen saturation is <90 % between 1 and 3 min after the end of a GTCS. Secondary outcomes will include the following: the proportion of patients who show postictal apnea, the occurrence and duration of postictal generalized EEG suppression, the total duration of the postictal coma, postictal pain, and the number of patients who have a second GTCS within 120 min after the intravenous injection.
The demonstration of naloxone's efficacy on the severity of postictal hypoxemia will have two primary consequences. First, naloxone would be the first and only therapeutic approach that could be delivered immediately to reverse postictal apnea. Second, demonstration that an opioid antagonist can effectively reduce postictal apnea would pave the way for an assessment of a preventive therapy for SUDEP targeting the same pathophysiological pathway using oral administration of naltrexone.
ClinicalTrials.gov identifier: NCT02332447 . Registered on 5 January 2015.</description><subject>Clinical Protocols</subject><subject>Convulsions & seizures</subject><subject>Double-Blind Method</subject><subject>Double-blind studies</subject><subject>Drug Administration Schedule</subject><subject>Drug overdose</subject><subject>Drug resistance</subject><subject>Electroencephalography</subject><subject>Electroencephalography - methods</subject><subject>Epilepsy</subject><subject>France</subject><subject>Humans</subject><subject>Hypotheses</subject><subject>Hypoxemia</subject><subject>Hypoxia - etiology</subject><subject>Hypoxia - physiopathology</subject><subject>Hypoxia - prevention & control</subject><subject>Injections, Intravenous</subject><subject>Life Sciences</subject><subject>Medication</subject><subject>Naloxone - administration & dosage</subject><subject>Naloxone - adverse effects</subject><subject>Narcotic Antagonists - administration & dosage</subject><subject>Narcotic Antagonists - adverse effects</subject><subject>Narcotics</subject><subject>Neurobiology</subject><subject>Neurons and Cognition</subject><subject>Oxygen saturation</subject><subject>Patients</subject><subject>Pharmaceutical sciences</subject><subject>Pharmaceuticals</subject><subject>Pulse oximetry</subject><subject>Research Design</subject><subject>Respiratory Center - drug effects</subject><subject>Respiratory Center - physiopathology</subject><subject>Respiratory Insufficiency - diagnosis</subject><subject>Respiratory Insufficiency - etiology</subject><subject>Respiratory Insufficiency - physiopathology</subject><subject>Respiratory Insufficiency - prevention & control</subject><subject>Seizures - complications</subject><subject>Seizures - diagnosis</subject><subject>Seizures - drug therapy</subject><subject>Seizures - physiopathology</subject><subject>Severity of Illness Index</subject><subject>Study Protocol</subject><subject>Time Factors</subject><subject>Treatment Outcome</subject><subject>Young adults</subject><issn>1745-6215</issn><issn>1745-6215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><recordid>eNpdUl1rFTEQXUSxtfoDfJGALwqu5nuzfRBKqVa44Is-h3xtm5KbrEm2uv4n_6O53GupfZph5pyZM8npupcIvkdI8A8FEchJDxHvEWekR4-6YzRQ1nOM2ON7-VH3rJQbCCkZCX3aHeFBwFFwcdz9uZgmb5RZQZpAVCH9StEBH0F2djE-XoE5lepNVQEYF2tuMbsy-6xqyiuwa5mWaKpPcceaVfUNVcBPX6-Bm31wc1lPQamLXcGcU00mBTClDBSwadHB9Tr4aN-BrKJNW__btXwOyjidepPaxhSCs6Bmr8Lz7smkQnEvDvGk-_7p4tv5Zb_5-vnL-dmmN5Sj2k9YCww55YINSgklGDEc08E4YgeohSXaYo0QxNpqPbYyttay9qbjRBieyEn3cT93XvTW2cPhcs5-q_Iqk_Ly_0701_Iq3UoGRwqJaAPe7gdcP6Bdnm3krgYRhXQU7BY17JvDspx-LK5UufXFuBBUdGkpEgnCBzwOI2zQ1w-gN2nJ7duKxMPIMCOc0oZCe5TJqZTspjsFCMqdceTeOE0ElzvjyJ2IV_cvvmP8cwr5C7dgwy4</recordid><startdate>20161103</startdate><enddate>20161103</enddate><creator>Rheims, Sylvain</creator><creator>Valton, Luc</creator><creator>Michel, Véronique</creator><creator>Maillard, Louis</creator><creator>Navarro, Vincent</creator><creator>Convers, Philippe</creator><creator>Bartolomei, Fabrice</creator><creator>Biraben, Arnaud</creator><creator>Crespel, Arielle</creator><creator>Derambure, Philippe</creator><creator>de Toffol, Bertrand</creator><creator>Hirsch, Edouard</creator><creator>Kahane, Philippe</creator><creator>Martin, Martine Lemesle</creator><creator>Tourniaire, Didier</creator><creator>Boulogne, Sébastien</creator><creator>Mercier, Catherine</creator><creator>Roy, Pascal</creator><creator>Ryvlin, Philippe</creator><general>BioMed Central</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>1XC</scope><scope>VOOES</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-1678-0297</orcidid><orcidid>https://orcid.org/0000-0001-6718-8210</orcidid><orcidid>https://orcid.org/0000-0003-4906-6855</orcidid><orcidid>https://orcid.org/0000-0001-8681-7369</orcidid><orcidid>https://orcid.org/0000-0003-3837-3198</orcidid><orcidid>https://orcid.org/0000-0002-4663-8515</orcidid><orcidid>https://orcid.org/0000-0003-0077-8114</orcidid></search><sort><creationdate>20161103</creationdate><title>Efficacy of naloxone in reducing postictal central respiratory dysfunction in patients with epilepsy: study protocol for a double-blind, randomized, placebo-controlled trial</title><author>Rheims, Sylvain ; Valton, Luc ; Michel, Véronique ; Maillard, Louis ; Navarro, Vincent ; Convers, Philippe ; Bartolomei, Fabrice ; Biraben, Arnaud ; Crespel, Arielle ; Derambure, Philippe ; de Toffol, Bertrand ; Hirsch, Edouard ; Kahane, Philippe ; Martin, Martine Lemesle ; Tourniaire, Didier ; Boulogne, Sébastien ; Mercier, Catherine ; Roy, Pascal ; Ryvlin, Philippe</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c461t-f2b820646857aa8a853c6247ce3d70b8d3bd2b1102bdbb9ce32ddd51189f352f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Clinical Protocols</topic><topic>Convulsions & seizures</topic><topic>Double-Blind Method</topic><topic>Double-blind studies</topic><topic>Drug Administration Schedule</topic><topic>Drug overdose</topic><topic>Drug resistance</topic><topic>Electroencephalography</topic><topic>Electroencephalography - methods</topic><topic>Epilepsy</topic><topic>France</topic><topic>Humans</topic><topic>Hypotheses</topic><topic>Hypoxemia</topic><topic>Hypoxia - etiology</topic><topic>Hypoxia - physiopathology</topic><topic>Hypoxia - prevention & control</topic><topic>Injections, Intravenous</topic><topic>Life Sciences</topic><topic>Medication</topic><topic>Naloxone - administration & dosage</topic><topic>Naloxone - adverse effects</topic><topic>Narcotic Antagonists - administration & dosage</topic><topic>Narcotic Antagonists - adverse effects</topic><topic>Narcotics</topic><topic>Neurobiology</topic><topic>Neurons and Cognition</topic><topic>Oxygen saturation</topic><topic>Patients</topic><topic>Pharmaceutical sciences</topic><topic>Pharmaceuticals</topic><topic>Pulse oximetry</topic><topic>Research Design</topic><topic>Respiratory Center - drug effects</topic><topic>Respiratory Center - physiopathology</topic><topic>Respiratory Insufficiency - diagnosis</topic><topic>Respiratory Insufficiency - etiology</topic><topic>Respiratory Insufficiency - physiopathology</topic><topic>Respiratory Insufficiency - prevention & control</topic><topic>Seizures - complications</topic><topic>Seizures - diagnosis</topic><topic>Seizures - drug therapy</topic><topic>Seizures - physiopathology</topic><topic>Severity of Illness Index</topic><topic>Study Protocol</topic><topic>Time Factors</topic><topic>Treatment Outcome</topic><topic>Young adults</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rheims, Sylvain</creatorcontrib><creatorcontrib>Valton, Luc</creatorcontrib><creatorcontrib>Michel, Véronique</creatorcontrib><creatorcontrib>Maillard, Louis</creatorcontrib><creatorcontrib>Navarro, Vincent</creatorcontrib><creatorcontrib>Convers, Philippe</creatorcontrib><creatorcontrib>Bartolomei, Fabrice</creatorcontrib><creatorcontrib>Biraben, Arnaud</creatorcontrib><creatorcontrib>Crespel, Arielle</creatorcontrib><creatorcontrib>Derambure, Philippe</creatorcontrib><creatorcontrib>de Toffol, Bertrand</creatorcontrib><creatorcontrib>Hirsch, Edouard</creatorcontrib><creatorcontrib>Kahane, Philippe</creatorcontrib><creatorcontrib>Martin, Martine Lemesle</creatorcontrib><creatorcontrib>Tourniaire, Didier</creatorcontrib><creatorcontrib>Boulogne, Sébastien</creatorcontrib><creatorcontrib>Mercier, Catherine</creatorcontrib><creatorcontrib>Roy, Pascal</creatorcontrib><creatorcontrib>Ryvlin, Philippe</creatorcontrib><creatorcontrib>ENALEPSY study group</creatorcontrib><creatorcontrib>on behalf of ENALEPSY study group</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Current controlled trials in cardiovascular medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rheims, Sylvain</au><au>Valton, Luc</au><au>Michel, Véronique</au><au>Maillard, Louis</au><au>Navarro, Vincent</au><au>Convers, Philippe</au><au>Bartolomei, Fabrice</au><au>Biraben, Arnaud</au><au>Crespel, Arielle</au><au>Derambure, Philippe</au><au>de Toffol, Bertrand</au><au>Hirsch, Edouard</au><au>Kahane, Philippe</au><au>Martin, Martine Lemesle</au><au>Tourniaire, Didier</au><au>Boulogne, Sébastien</au><au>Mercier, Catherine</au><au>Roy, Pascal</au><au>Ryvlin, Philippe</au><aucorp>ENALEPSY study group</aucorp><aucorp>on behalf of ENALEPSY study group</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Efficacy of naloxone in reducing postictal central respiratory dysfunction in patients with epilepsy: study protocol for a double-blind, randomized, placebo-controlled trial</atitle><jtitle>Current controlled trials in cardiovascular medicine</jtitle><addtitle>Trials</addtitle><date>2016-11-03</date><risdate>2016</risdate><volume>17</volume><issue>1</issue><spage>529</spage><epage>529</epage><pages>529-529</pages><artnum>529</artnum><issn>1745-6215</issn><eissn>1745-6215</eissn><abstract>Generalized tonic-clonic seizures (GTCSs) are the main risk factor for sudden unexpected death in epilepsy (SUDEP). Experimental and clinical data strongly suggest that the majority of SUDEP results from a postictal respiratory dysfunction progressing to terminal apnea. Postictal apnea could partly derive from a seizure-induced massive release of endogenous opioids. The main objective of this study is to evaluate the efficacy of an opioid antagonist, naloxone, administered in the immediate aftermath of a GTCS, in reducing the severity of the postictal central respiratory dysfunction.
The Efficacy of Naloxone in Reducing Postictal Central Respiratory Dysfunction in Patients with Epilepsy (ENALEPSY) study is a multicenter, double-blind, randomized, placebo-controlled trial conducted in patients with drug-resistant focal epilepsy who are undergoing long-term video-electroencephalogram (EEG) monitoring (LTM) in an epilepsy monitoring unit (EMU). We plan to randomize 166 patients (1:1) to receive intravenous naloxone (0.4 mg) or placebo in the immediate aftermath of a GTCS. Because inclusion in the study needs to take place prior to the occurrence of the GTCS, and because such occurrence is observed in about one-fourth of patients undergoing LTM, we plan to include a maximum of 700 patients upon admission in the EMU. The primary endpoint will be the proportion of patients whose oxygen saturation is <90 % between 1 and 3 min after the end of a GTCS. Secondary outcomes will include the following: the proportion of patients who show postictal apnea, the occurrence and duration of postictal generalized EEG suppression, the total duration of the postictal coma, postictal pain, and the number of patients who have a second GTCS within 120 min after the intravenous injection.
The demonstration of naloxone's efficacy on the severity of postictal hypoxemia will have two primary consequences. First, naloxone would be the first and only therapeutic approach that could be delivered immediately to reverse postictal apnea. Second, demonstration that an opioid antagonist can effectively reduce postictal apnea would pave the way for an assessment of a preventive therapy for SUDEP targeting the same pathophysiological pathway using oral administration of naltrexone.
ClinicalTrials.gov identifier: NCT02332447 . Registered on 5 January 2015.</abstract><cop>England</cop><pub>BioMed Central</pub><pmid>27809868</pmid><doi>10.1186/s13063-016-1653-1</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-1678-0297</orcidid><orcidid>https://orcid.org/0000-0001-6718-8210</orcidid><orcidid>https://orcid.org/0000-0003-4906-6855</orcidid><orcidid>https://orcid.org/0000-0001-8681-7369</orcidid><orcidid>https://orcid.org/0000-0003-3837-3198</orcidid><orcidid>https://orcid.org/0000-0002-4663-8515</orcidid><orcidid>https://orcid.org/0000-0003-0077-8114</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1745-6215 |
| ispartof | Current controlled trials in cardiovascular medicine, 2016-11, Vol.17 (1), p.529-529, Article 529 |
| issn | 1745-6215 1745-6215 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5094038 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; PubMed Central Open Access; Springer Nature OA Free Journals; Springer Nature - Complete Springer Journals; PubMed Central |
| subjects | Clinical Protocols Convulsions & seizures Double-Blind Method Double-blind studies Drug Administration Schedule Drug overdose Drug resistance Electroencephalography Electroencephalography - methods Epilepsy France Humans Hypotheses Hypoxemia Hypoxia - etiology Hypoxia - physiopathology Hypoxia - prevention & control Injections, Intravenous Life Sciences Medication Naloxone - administration & dosage Naloxone - adverse effects Narcotic Antagonists - administration & dosage Narcotic Antagonists - adverse effects Narcotics Neurobiology Neurons and Cognition Oxygen saturation Patients Pharmaceutical sciences Pharmaceuticals Pulse oximetry Research Design Respiratory Center - drug effects Respiratory Center - physiopathology Respiratory Insufficiency - diagnosis Respiratory Insufficiency - etiology Respiratory Insufficiency - physiopathology Respiratory Insufficiency - prevention & control Seizures - complications Seizures - diagnosis Seizures - drug therapy Seizures - physiopathology Severity of Illness Index Study Protocol Time Factors Treatment Outcome Young adults |
| title | Efficacy of naloxone in reducing postictal central respiratory dysfunction in patients with epilepsy: study protocol for a double-blind, randomized, placebo-controlled trial |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-15T08%3A23%3A23IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Efficacy%20of%20naloxone%20in%20reducing%20postictal%20central%20respiratory%20dysfunction%20in%20patients%20with%20epilepsy:%20study%20protocol%20for%20a%20double-blind,%20randomized,%20placebo-controlled%20trial&rft.jtitle=Current%20controlled%20trials%20in%20cardiovascular%20medicine&rft.au=Rheims,%20Sylvain&rft.aucorp=ENALEPSY%20study%20group&rft.date=2016-11-03&rft.volume=17&rft.issue=1&rft.spage=529&rft.epage=529&rft.pages=529-529&rft.artnum=529&rft.issn=1745-6215&rft.eissn=1745-6215&rft_id=info:doi/10.1186/s13063-016-1653-1&rft_dat=%3Cproquest_pubme%3E2795253644%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2795253644&rft_id=info:pmid/27809868&rfr_iscdi=true |